TR201815292T4 - İnsüli̇n duyarliliğinin tedavi̇si̇nde melanokorti̇nleri̇n kullanimi. - Google Patents
İnsüli̇n duyarliliğinin tedavi̇si̇nde melanokorti̇nleri̇n kullanimi. Download PDFInfo
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- TR201815292T4 TR201815292T4 TR2018/15292T TR201815292T TR201815292T4 TR 201815292 T4 TR201815292 T4 TR 201815292T4 TR 2018/15292 T TR2018/15292 T TR 2018/15292T TR 201815292 T TR201815292 T TR 201815292T TR 201815292 T4 TR201815292 T4 TR 201815292T4
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- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
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- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
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- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/33—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin
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Abstract
Mevcut buluş, melanokortin reseptörlerinin, özellik ile de melanokortin-4 reseptörünün peptid ligandları ile ilgilidir ve bu itibarla, insülin direnci gibi bu reseptörün aktivasyonuna duyarlı rahatsızlıkların tedavi edilmesinde yararlıdır.
Description
TARIFNAME
INSÜLIN DUYARLILlGININ TEDAVISINDE MELANOKORTINLERIN KULLANIMI
TEKNIGIN BILINEN DURUMU
Melanokortinler proopiomelanokortin prohormonun (POMC; 131 amino asit uzunlugunda)
translasyon sonrasi (post-trabslational) proses ile olusan düzenleyici peptit ailesidir. POMC
üç hormon sinifinda islenmektedir: melanokortinler, adrenokortikotropin hormonu ve çesitli
endorfinler (örnegin, Iipotropin) (Cone ve arkadaslari, Recent Prog. Horm. Res., 51:287-317,
Bugüne kadar bes melanokortin reseptörü (MC-R) karakterize edilmistir. Bunlar, melanosit
spesifik reseptör (MC1-R), kortikoadrenal spesifik ACTH reseptörü (MC2-R), melakortin-3
(MCS-R), melanokortin-4 (MC4-R) ve melanokortin-5 reseptörü (MC5-R). Bütün melanokortin
reseptörleri melanosit uyarici peptit hormon sinifi hormonlara (MSH) tepki gösterir (Cone ve
Obezite ve kaseksi gibi vücut agirligi bozukluklarinin tedavisi için yeni tedavilerin
gelistirilmesinde hedef olarak melanokortin (MC-R) reseptörlerine büyük ilgi gösterilmektedir.
Reseptörlerden birisi olan MC4-R, beyinde ve ayni zamanda plasenta ve bagirsak
dokularinda eksprese olan 332 amino asit membran geçisini saglayan (transmembran)
reseptörlerinin sirasi ile melanokortin agonistleri ve antagonistleri üzerinde rapor edilen
anoreksik ve oreksijenik etkilerin baslica mediyatörü oldugu farmakolojik onaylama ile
Vücut agirligi bozukluklari ile ilgili komplikasyonlar, genellik ile hatali glikoz regülasyonuna
yol açan insülin üretme ve kullanma yetersizligini içerir. Glikoz metabolizmasinin dogru
kontrol edilememesi, enerji metabolizmasi, nöropati ve kalp hastaligi gibi genel sagligin pek
çok yönünü etkileyen sonuçlar dogurur. Reseptör seçici melanokortin reseptörü Iigandlari ile
ilgili ilerlemeler melanokortin reseptörü aktivasyonunun, özellik ile de MC4-R'nin insülin
metabolizmasini da içeren glikoz regülasyonu tedavisindeki iyilestirici potansiyelini
kanitlamaktadir.
gibi etki eden tanimli bilesikler ile ve ayni zamanda bilesikleri kullanma yöntemleri ve
bilesikleri içeren farmakolojik terkipler ile ilgilidir.
gibi etki eden tanimli bilesikler ile ve ayni zamanda bilesikleri kullanma yöntemleri ve
bilesikleri içeren farmakolojik terkipler ile ilgilidir.
Fan W ve arkadaslarinin, "Merkezi Melanokortin Sistemi Serum Insülin Seviyelerini
Dogrudan Düzenleyebilir" baslikli arastirmasinda (Endokrinoloji (2000) cilt 141, n0.9,
sayfa 3072-3079) merkezi olarak verilen melanokortin agonistlerinin bazal insülin
salinimini inhibe ettigi ve glikoz toleransini degistirdigi rapor edilmektedir.
Heijboer A C ve arkadaslarinin, "Intraserebroventriküler yol ile verilen melanotan II
farelerde glikoz kullaniminda insülin duyarliligini arttirmaktadir” baslikli çalismasinda
(Diabetologia; Clinical and Experimental Diabetes and Metabolism, Springer, Berlin
reseptörü agonisti melanotan II 'nin alinan gidalardan ve vücut agirligindan bagimsiz
olarak hepatik ve tüm vücudun insülin duyarliligi üzerindeki etkileri
degerlendirilmektedir.
Banno R ve arkadaslarinin, "Melanokortin agonist melanotan II OLETF siçanlarda
insülin duyarliligini arttirmaktadir” (Peptides, Elsevier, Amsterdam (2004) cilt 25, no.8,
sayfa1279-1286) baslikli çalismasinda periferik yol ile verilen melanokortin agonisti
melanotan II 'nin OLETF siçanlarinda insülin duyarliligina ve glikoz toleransina olan
etkileri incelenmektedir.
WO 2008/1566?? A2 patent yayini, mevcut basvurunun en erken ilk basvuru tarihinden
önceki en erken basvuru tarihine sahiptir ve mevcut basvurunun basvuru tarihinden sonra
yayinlanmistir. Doküman, bir veya birden fazla melanokortin reseptörü için ligand gibi etki
eden tanimli bilesikler ile ve ayni zamanda bilesikleri kullanma yöntemleri ve bilesikleri içeren
farmakolojik terkipler ile ilgilidir.
önceki en erken basvuru tarihine sahiptir ve mevcut basvurunun basvuru tarihinden sonra
yayinlanmistir. Doküman, bir veya birden fazla melanokortin reseptörü için ligand gibi etki
eden tanimli bilesikler ile ve ayni zamanda bilesikleri kullanma yöntemleri ve bilesikleri içeren
farmakolojik terkipler ile ilgilidir.
US 6,689,938 82 patent yayini, hastanin insülin direncinin azaltilmasina yardimci olan
bilesikleri tanimlama yöntemi ve tanimlanan bilesik verilerek hastanin insülin direncini
azaltma yöntemleri ile ilgilidir.
BU LUSUN ÖZETI
Mevcut patent hakki bildirimi, insülin direncinden muzdarip olan memelilerin tedavisinde bir
veya birden fazla melanokortin reseptörünün (MC-R) Iigandlari olan peptitlerin veya bunlarin
farmasötik olarak kabul edilen tuzlarinin kullanimina yöneliktir. Bir uygulamada, Iigandlar
melanokortin 4 reseptörünün agonistleridir. Bir uygulamada, melanokortin reseptörüne
baglanan Iigandlar burada belirtilen formüle uygundur veya burada tarif edilen belirli
peptitlerden seçilmistir.
insüline dirençli denek memeliler obez veya fazla kilolu olabilir ve burada belirtilen peptitlerin
verilmesinin sonucunda kilo kaybetmis olabilir. Insülin dirençli denek memeliler normal kilolu
veya zayif da olabilir. Denek memelilerin insülin direnci rahatsizligi kilo kaybindan bagimsiz
olarak tedavi edilebilir. Buna ilaveten, denek memeliler bebek, çocuk, yetiskin veya yasli
yetiskin gibi herhangi bir yasta insan denekler olabilir.
Buna göre, bulusun bir uygulamasinda denegin insülin direncinin tedavisinde periferik yol ile
verilen melanokortin reseptörü 4 agonisti kullanilmaktadir, burada söz konusu melanokortin
reseptörü 4 agonisti:
Hydantoin(C(O)-(Arg-GIy))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NHz; SEQ ID No:278;
veya farmasötik olarak kabul edilen tuzudur.
Bulusun diger uygulamalari mevcut istemlerde açiklanmistir.
Ayrica burada memeli denekte insülin direncini kilo vererek veya kilo vermeden, terapötik
etkili miktarda Formül (I) 'e uygun melanokortin reseptörü 4 Iigandinin ve bunlarin farmasötik
olarak kabul edilen tuzlarinin, hidratlarinin, solvatlarinin veya ön ilaçlarinin verilmesi yolu ile
tedavi etme yöntemi tarif edilmektedir (bkz. Uluslararasi Patent Basvurusu Yayin No. WO
A1 Acc, HN-(CH2)m-C(O), L- veya D-amino asit, veya çikarilmis; A2 , Cys, D-Cys,
hCys, D-hCys, Pen. D-Pen, Asp, veya Glu dur; A3 ,Gly, Ala, ß-Ala, Gaba, Aib, D-
amino asit veya çikarilmis; A4 His dir, 2-Pal, 3-Pal, 4-Pal, Taz, 2-Thi, 3-Thi, veya
(X1,X2,X3,X4,X5)Phe; A5 D-Phe dir, D-1-Nal, D-2-Nal, D-Trp, D-Bal, D-
(X1,X2,X3,X4,X5)Phe, L-Phe veya D-(Et)Tyr; A6 Arg dir, hArg, Dab, Dap, Lys, Orn, veya
HN-CH((CH2)n-N(R4R5))-C(O); A7 Trp dir, 1-Nal, 2-Nal, Bal, Bip, D-Trp, D-1-Nal, D-2-
Nal, D-Bal veya D-Bip; A8 Gly dir, D-Ala, Acc, Ala, ß-Ala, Gaba, Apn, Ahx, Aha, HN-
(CH2)s-C(O), veya çikarilmis; A9 Cys dir, D-Cys, hCys, D-hCys, Pen, D-Pen, Dab,
Dap, Orn, veya Lys; A10 Acc dir, HN-(CH2)t-C(O), L- veya D-amino asit veya
çikarilmis; R1 OH veya NH2; R2 ve Ra'ün her birisi, H, (Ci-C3o)alkil, (C1-Cgo)heteroalkil,
(C1'C3o)aSII, (Cz-C30)alkenil, (Cz-Cao)alkinil, ariI(Ci-C30)alkil, ariI(Ci-C30)asil, ikameli
(Ci-Cso)alkil, ikameli (Ci-Cgo)heteroalkil, ikameli (Ci-C30)aSI|, ikameli (Cg-Cao)alkenil,
ikameli (Cz-C30)alkinil, ikameli ariI(Ci-C30)alkil, ve ikameli ariI(Ci-C30)asil içeren
gruptan seçilen her vaka için bagimsiz olarak; R4 ve R5'In her birisi, her vaka için
bagimsiz olarak, H, (C1-C40)aIkII, (C1-C4o)heteroalkil, (Ci-C4o)asil, (Cg-C4o)alkenil, (CZ-
C40)alkinil, ariI(Ci-C40)a|kil, ariI(C1-C40)asil, ikameli (Ci-C4o)alkil, ikameli (Ci-
C40)heter0alkil, ikameli (Ci-C40)aSiI, ikameli (Cz-C40)alkenil, ikameli (Cz-C40)alkinil,
ikameli ariI(Ci-C40)alkil, ikameli ariI(Ci-Cio)asil, (Ci-C4o)alkilsulfonil, veya -C(NH)-
NH2;m, her vaka için bagimsiz olarak, 1, 2, 3, 4, 5, 6 veya 7; n, her vaka için
veya 7 'dir;
t, her vaka için bagimsiz olarak, 1, 2, 3, 4, 5, 6, veya 7 'dir;
X1, X2, X3, X4, ve X5 her birisi, her vaka için bagimsiz olarak, H, F, CI, Br, I, (Ci.
io)alkinil, aril, ikameli aril, OH, NH2, N02, veya CN; su kosulla ki
(i). R4 (Ci-C40)asil, ariI(Ci-C4o)asil, ikameli (Ci-C4o)asil, ikameli ariI(C1-C4o)asil,
(C1-C4o)a|kilsulfonil, veya -C(NH)-NH2 ise, bu durumda R5 H veya (Ci-C40)alkil,
(Ci-C4o)heteroalkil, (Cz-C40)alkenil, (Cz-C4o)alkinil, ariI(Ci-C40)alkil, ikameli (Ci-
C40)alkil, ikameli (Ci-C40)heteroalkil, ikameli (Cz-C40)alkenil, ikameli (Cz-
C40)alkinil, veya ikameli ariI(C1-C40)alkildir;
(II). R2 (C1-C30)aSII, ariI(Ci-C30)asil, ikameli (Ci-Cao)asil, veya ikameli ariI(C1-
C30)aSI| ise, bu durumda R3 H, (Ci-C30)alkil, (Ci-C30)heter0alkil, (Cg-Cao)alkenil,
(Cz-Cga)alkinil, ariI(C1-Cgo)alkil, ikameli (C1'Cgo)aikil, ikameli (C1-Cga)heteroalkil,
ikameli (Cz-Cgo)alkenil, ikameli (Cz-C30)alkinil veya ikameli ariI(C1-C30)alkildir;
(III). Söz konusu bilesikde A3 veya A8 veya her ikisi birden bulunmalidir;
(IV). A2 Cys, D-Cys, hCys, D-hCys, Pen, or D-Pen ise, bu durumda Ag Cys, D-
Cys, hCys, D-hCys, Pen, ve D-Pen'dir;
(V). A2 Asp veya Glu ise, bu durumda A9 Dab, Dap, Orn, veya Lys'dir;
(VI). A8 Ala veya Gly ise, bu durumda A1 Nle degildir; ve
(W). A1 çikarilmis ise, bu durumda R2 ve R3 “ün her ikisi birden H olamaz;
veya bunlarin farmasötik olarak kabul edilen tuzlari.
Burada tarif edilen bir uygulama, memeli denegin insülin direncini kilo kaybederek veya kilo
kaybi olmadan, hemen yukaridaki Formül I 'nin melanokortin reseptörü Iigand alt grubunun
terapötik etkili miktarda verilmesi ile tedavi eden bir yöntemdir, burada
A1 , Aöc, Arg, D-Arg, Cha, D-Cha, hCha, Chg, D-Chg, Gaba, Ile, Leu, hLeu, Met, ß-
hMet, 2-Nal, D-2-Nal, Nip, Nle, Oic, Phe, D-Phe, hPhe. hPro, Val, veya çikarilmistir;
A2 , Asp, Cys, D-Cys, hCys, D-hCys, Glu, Pen, veya D-Pen dir;
A3 , D-Abu, Aib, Ala, ß-Ala, D-Ala, D-Cha, Gaba, D-Glu, Gly, D-Ile, D-Leu, D-Tle, D-
Val, veya çikarilmistir;
A4 , His veya 3-Pai dir;
A5 , D-Bal, D-1-Nal, D-2-Nal, D-Phe, D-Trp, veya D-(Et)Tyr dir;
A6 , Arg, veya hArg dir;
A7 , Bal, Bip, 1-Nal, 2-Nal, Trp, D-Trp dir;
A8 , Aöc, D-Ala, Aha, Ahx, Ala, ß-Ala, Apn, Gaba, Gly veya çikarilmistir;
A9 , Cys, D-Cys, hCys, D-hCys, Lys, Pen, veya D-Pen dir;
burada A3 veya A8 den en az birisi, ancak her ikisi birden degil, çikarilmistir,
veya bunlarin farmasötik olarak kabul edilen tuzlari.
Memeli denegin, kilo kaybederek veya kilo kaybi olmadan insülin direncinin tedavisinde
yararli olan hemen yukaridaki bilesik grubunun Formül (I) 'e uygun Iigand örnekleri asagidaki
formülün bilesikleridir:
Ac-NIe-C(Asp-His-D-Phe-Arg-Trp-ß-AIa-Lys)-NHz; SEO ID NO:1
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-AGc-Lys)-NH2; SEQ ID No:1
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-NHz; SEQ ID No:2
D-Phe-c(Cys-His-D-Phe-Arg-Trp-Ala-D-Cys)-Thr-NHz; SEQ ID No:3
D-Phe-c(Cys-His-D-Phe-Arg-Trp-ß-AIa-D-Cys)-Thr-NHz; SEQ ID NO:3
D-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-D-Cys)-Thr-NH2; SEQ ID No:3
Ac-NIe-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NHz; SEQ ID No:2
Ac-NIe-c(Asp-His-D-Phe-Arg-Trp-Apn-Lys)-NHz; SEQ lD No:4
Ac-Aöc-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; SEQ ID NO:5
Ac-D-2-NaI-C(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; SEQ ID NO:6
AC-Cha-C(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NHz; SEQ ID No:6
Ac-NIe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NHz; SEO ID No:6
Ac-Nle-C(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-NHz; SEO ID No:7
Ac-NIe-c(Cys-ß-AIa-His-D-Phe-Arg-Trp-Cys)-NHz; SEO ID No:7
Ac-NIe-c(Cys-Gaba-His-D-Phe-Arg-Trp-Cys)-NHz; SEO ID No:7
Ac-NIe-c(Cys-Aib-His-D-Phe-Arg-Trp-Cys)-NHz; SEO ID No:7
Ac-NIe-c(Cys-GIy-His-D-Phe-Arg-Trp-Cys)-NHz; SEO ID No:7
Ac-NIe-c(D-Cys-AIa-His-D-Phe-Arg-Trp-Cys)-NH2; SEO ID No:8
Ac-NIe-c(D-Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-NHz; SEO ID No:8
Ac-NIe-c(D-Cys-ß-AIa-His-D-Phe-Arg-Trp-Cys)-NHz; SEO ID No:8
Ac-NIe-c(D-Cys-Gaba-His-D-Phe-Arg-Trp-Cys)-NH2; SEO ID No:8
Ac-NIe-c(D-Cys-Aib-His-D-Phe-Arg-Trp-Cys)-NH2; SEO ID No:8
Ac-NIe-C(D-Cys-GIy-His-D-Phe-Arg-Trp-Cys)-NH2; SEO ID No:8
Ac-NIe-C(Cys-D-AIa-His-D-Phe-Arg-Trp-D-Cys)-NHz; SEO ID No:9
Ac-NIe-C(Cys-ß-AIa-His-D-Phe-Arg-Trp-D-Cys)-NHZ; SEO lD No:9
Ac-NIe-c(Cys-Gaba-His-D-Phe-Arg-Trp-D-Cys)-NH2; SEO ID No:9
Ac-NIe-c(Cys-Aib-His-D-Phe-Arg-Trp-D-Cys)-NHz; SEO ID No:9
Ac-NIe-c(Cys-GIy-His-D-Phe-Arg-Trp-D-Cys)-NH2; SEO ID No:9
Ac-NIe-c(D-Cys-AIa-His-D-Phe-Arg-Trp-D-Cys)-NHz; SEO lD NO:10
Ac-NIe-c(D-Cys-D-AIa-His-D-Phe-Arg-Trp-D-Cys)-NH2; SEO ID NO:10
Ac-NIe-c(D-Cys-ß-AIa-His-D-Phe-Arg-Trp-D-Cys)-NH2; SEO ID NO:10
Ac-NIe-c(D-Cys-Gaba-His-D-Phe-Arg-Trp-D-Cys)-NH2; SEO ID NO:10
Ac-NIe-C(D-CyS-Aib-His-D-Phe-Arg-Trp-D-Cys)-NHz; SEO ID NO:10
AC-OiC-C(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; SEO ID NO:11
Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NHz; SEO ID NO:11
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NHz; SEO ID NO:11
Ac-D-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; SEO ID NO:11
Ac-Nip-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NHz; SEO ID NO:11
Ac-hPro-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NHz; SEO ID NO:11
Ac-hLeu-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NHz; SEO ID NO:11
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; SEO lD NO:11
Ac-Phe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; SEO ID NO:11
Ac-D-Phe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; SEO ID NO:11
Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; SEO lD NO:11
n-butanoyl-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; SEO ID NO:12
Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; SEO ID NO:11
Ac-ß-hMet-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; SEO ID NO:11
AC-Gaba-C(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; SEQ ID NO:11
Ac-Cha-c(Asp-His-D-Phe-Arg-D-Trp-AIa-Lys)-NHz; SEQ ID NO:13
Ac-hCha-c(Asp-His-D-Phe-Arg-D-Trp-AIa-Lys)-NH2; SEQ lD NO:13
Ac-Leu-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NHz; SEQ ID NO:13
Ac-hLeu-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NHz; SEQ ID NO:13
Ac-Phe-C(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2; SEQ ID NO:13
Ac-NIe-c(Asp-His-D-Phe-Arg-D-Trp-D-AIa-Lys)-NHz; SEQ ID NO:14
Ac-NIe-c(Asp-His-D-Phe-Arg-D-Trp-ß-Ala-Lys)-NH2; SEQ lD NO:14
Ac-NIe-c(Asp-His-D-Phe-Arg-D-Trp-Gaba-Lys)-NH2; SEQ ID NO:14
Ac-NIe-c(Asp-His-D-Phe-Arg-D-Trp-Aha-Lys)-NH2; SEQ ID NO:14
Ac-NIe-c(Asp-His-D-Phe-Arg-D-Trp-Apn-Lys)-NHz; SEQ ID NO:14
Ac-NIe-C(CyS-His-D-Phe-Arg-D-Trp-Apn-CyS)-NH2; SEQ ID NO:15
Ac-NIe-c(Cys-His-D-Phe-Arg-D-Trp-Gaba-Cys)-NH2; SEQ ID NO:15
Ac-NIe-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-NHz; SEQ lD NO:15
Ac-NIe-C(Cys-His-D-Phe-Arg-D-Trp-ß-AIa-Cys)-NHz; SEQ ID NO:15
Ac-NIe-c(Cys-His-D-Phe-Arg-D-Trp-D-AIa-Cys)-NHz; SEQ ID NO:15
Ac-NIe-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2; SEQ ID NO:16
Ac-NIe-c(Cys-D-Ala-His-D-2-NaI-Arg-2-NaI-Cys)-NH2; SEQ ID NO:16
Ac-NIe-C(Cys-D-AIa-His-D-2-NaI-Arg-1-NaI-Cys)-NH2; SEQ ID NO:16
n-butanoyl-NIe-C(Cys-D-AIa-His-D-Phe-Arg-Z-NaI-Cys)-NHz; SEQ ID NO:17
n-butanoyI-NIe-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-NH2; SEQ ID NO:17
Ac-NIe-c(Cys-D-AIa-His-D-Phe-Arg-2-NaI-CyS)-NHz; SEQ ID NO:18
Ac-NIe-c(Cys-D-AIa-His-D-Phe-Arg-1-NaI-Cys)-NH2; SEQ ID NO:18
Ac-NIe-C(Cys-D-Ala-His-D-Phe-Arg-BaI-Cys)-NH2; SEQ ID NO:18
Ac-NIe-c(Cys-D-GIu-His-D-Phe-Arg-Trp-Cys)-NH2; SEQ ID NO:61
Ac-NIe-c(Asp-His-D-Phe-Arg-Trp-D-AIa-Lys)-NHz; SEQ ID NO:19
Ac-NIe-C(Cys-D-AIa-His-D-2-NaI-Arg-Bal-Cys)-NH2; SEQ ID NO:20
Ac-NIe-c(Pen-D-AIa-His-D-Phe-Arg-Trp-Cys)-NH2; SEQ ID NO:21
Ac-NIe-C(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; SEQ ID NO:22
Ac-NIe-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Pen)-NHz; SEQ ID NO:22
D-Phe-c(Cys-His-D-Phe-hArg-Trp-ß-Ala-D-Cys)-Thr-NHz; SEQ ID NO:23
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-ß-Ala-D-Cys)-Thr-NH2; SEQ ID NO:24
D-Phe-C(Cys-His-D-Phe-Arg-Bip-ß-AIa-D-Cys)-Thr-NHz; SEQ ID NO:25
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-ß-Ala-D-Cys)-Thr-NHz; SEQ ID NO:24
D-Phe-c(Cys-His-D-Phe-hArg-Bip-ß-AIa-D-Cys)-Thr-NH2; SEQ ID NO:26
D-Phe-C(Cys-His-D-(Et)Tyr-hArg-Bip-ß-AIa-D-Cys)-Thr-NHz; SEQ ID NO:26
NIe-c(Cys-HIs-D-Phe-Arg-Trp-Apn-Cys)-NHz; SEQ ID NO:27
Ac-NIe-C(Asp-D-Ala-His-D-Phe-Arg-Trp-Lys)-NHz; SEO ID NO:28
Ac-NIe-c(Asp-D-Ala-His-D-Phe-Arg-BaI-Lys)-NHz; SEO ID NO:28
Ac-NIe-C(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-OH; SEO ID NO:29
Ac-NIe-c(Cys-D-Abu-His-D-Phe-Arg-Trp-Cys)-NHz; SEO ID NO:30
Ac-NIe-c(Cys-D-VaI-His-D-Phe-Arg-Trp-Cys)-NHz; SEO ID NO:30
Ac-NIe-c(Cys-D-IIe-His-D-Phe-Arg-Trp-Cys)-NH2; SEO ID NO:30
Ac-NIe-c(Cys-D-Leu-HIs-D-Phe-Arg-Trp-Cys)-NHz; SEO ID NO:30
Ac-NIe-c(Cys-D-TIe-His-D-Phe-Arg-Trp-Cys)-NHz; SEO ID NO:30
Ac-NIe-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-NH2; SEO ID NO:30
Ac-NIe-c(Pen-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; SEO ID NO:31
Ac-NIe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NHz; SEO ID NO:32
Ac-NIe-c(Pen-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; SEO ID NO:32
AC-Leu-C(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NHz; SEO ID NO:33
Ac-Cha-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NHz; SEO ID NO:33
Ac-IIe-C(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NHz; SEO ID NO:33
Ac-Phe-C(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NHz; SEO ID NO:33
Ac-VaI-C(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NHz; SEO ID NO:33
Ac-2-Nal-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NHz; SEO ID NO:33
NIe-C(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NHz; SEO ID NO:34
Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NHz; SEO ID NO:34
Ac-NIe-c(Cys-3-PaI-D-Phe-Arg-Trp-Gaba-Cys)-NH2; SEO ID NO:35
Ac-NIe-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-OH; SEO ID NO:36
Ac-NIe-c(Cys-His-Phe-Arg-D-Trp-Gaba-Cys)-NHz; SEO ID NO:37
Ac-NIe-C(Asp-His-D-2-NaI-Arg-Trp-AIa-Lys)-NH2; SEO ID NO:38
Ac-NIe-c(Asp-His-D-2-NaI-Arg-Trp-ß-AIa-Lys)-NH2; SEO ID NO:38
Ac-NIe-c(Cys-His-D-2-NaI-Arg-Trp-Gaba-Cys)-NHz; SEO ID NO:39
Ac-NIe-c(Cys-His-D-2-NaI-Arg-Trp-Ahx-Cys)-NHz; SEO ID NO:39
Ac-hPhe-c(Asp-His-D-2-NaI-Arg-Trp-Gaba-Lys)-NHz; SEO ID NO:40
Ac-Cha-c(Asp-His-D-2-NaI-Arg-Trp-Gaba-Lys)-NH2; SEO ID NO:40
Ac-NIe-c(Asp-His-D-Phe-Arg-Trp-ß-AIa-Lys)-OH; SEO ID NO:41
Ac-NIe-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-OH; SEO ID NO:42
D-Phe-C(Cys-His-D-Phe-Arg-Trp-Ala-D-Cys)-Thr-OH; SEO ID NO:43
D-Phe-C(Cys-His-D-Phe-Arg-Trp-ß-AIa-D-Cys)-Thr-OH; SEO ID NO:43
D-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-D-Cys)-Thr-OH; SEO ID NO:43
Ac-NIe-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-OH; SEO ID NO:42
Ac-NIe-c(Asp-His-D-Phe-Arg-Trp-Apn-Lys)-OH; SEO ID NO:41
Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; SEO ID NO:44
Ac-NIe-C(Asp-His-D-Phe-Arg-Trp-Gaba-LyS)-OH; SEO ID NO:44
Ac-NIe-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-OH; SEO ID NO:29
Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; SEO lD NO:44
Ac-D-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; SEO ID NO:44
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; SEO ID NO:44
Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; SEO ID NO:44
Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; SEO ID NO:44
Ac-NIe-c(Cys-His-D-Phe-Arg-D-Trp-Gaba-Cys)-OH; SEO ID NO:45
Ac-NIe-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-OH; SEO ID NO:45
Ac-NIe-c(Cys-His-D-Phe-Arg-D-Trp-ß-AIa-Cys)-OH; SEO ID NO:45
Ac-NIe-c(Cys-His-D-Phe-Arg-D-Trp-D-AIa-Cys)-OH; SEO ID NO:45
Ac-NIe-C(Cys-D-AIa-His-D-2-Nal-Arg-Trp-Cys)-OH; SEO ID NO:46
Ac-NIe-c(Cys-D-Ala-His-D-2-NaI-Arg-2-NaI-Cys)-OH; SEO ID NO:46
Ac-NIe-C(Cys-D-AIa-His-D-2-NaI-Arg-1-NaI-Cys)-OH; SEO ID NO:46
Ac-NIe-C(Cys-D-AIa-His-D-Z-NaI-Arg-BaI-Cys)-OH; SEO ID NO:46
Ac-NIe-c(Pen-D-AIa-His-D-Phe-Arg-Trp-Cys)-OH; SEO ID NO:47
Ac-NIe-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-OH; SEO ID NO:29
Ac-NIe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-OH; SEO ID NO:48
Ac-Arg-c(Cys-D-Ala-His-D-2-NaI-Arg-Trp-Cys)-NH2; SEO lD NO:49
Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; SEO ID NO:50
Ac-D-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; SEO ID NO:50
Ac-D-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; SEO ID NO:51
Ac-D-Arg-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; SEO ID NO:52
AC-Arg-C(CyS-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; SEQ ID NO:52
Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NHz; SEO ID NO:51
Ac-D-Arg-c(Asp-His-D-Phe-Arg-Trp-AIa-Lys)-NHz; SEO ID NO:53
Ac-Arg-c(Asp-His-D-Phe-Arg-Trp-AIa-Lys)-NH2; SEO ID NO:53
Ac-NIe-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-NH2; SEO ID No:7
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-ß-Ala-D-Cys)-Thr-NH2; SEO ID NO:24
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NHz; SEO ID NO:27
Ac-NIe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NHz; SEO ID NO:32
NIe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NHz; SEO ID NO:34
Ac-NIe-c(Asp-His-D-Phe-Arg-Trp-ß-AIa-Lys)-NH2; SEO ID NO:1
Ac-NIe-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-NH2; SEO ID No:2
D-Phe-c(Cys-His-D-Phe-Arg-Trp-ß-AIa-D-Cys)-Thr-NHz; SEO ID No:3
D-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-D-Cys)-Thr-NHz; SEO ID No:3
AC-NIe-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NHz; SEO ID No:2
Ac-NIe-C(Asp-His-D-Phe-Arg-Trp-Apn-Lys)-NH2; SEO ID NO:4
Ac-Cha-0(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NHz; SEO ID No:6
Ac-NIe-C(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NHz; SEO lD No:6
Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NHz; SEO ID NO:11
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NHz; SEO ID NO:11
Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; SEO ID NO:11
Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; SEO ID NO:11
Ac-NIe-c(Cys-His-D-Phe-Arg-D-Trp-ß-AIa-Cys)-NHz; SEO lD NO:15
Ac-NIe-C(Pen-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; SEO ID NO:21
Ac-NIe-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Pen)-NH2; SEO ID NO:22
D-Phe-c(Cys-His-D-Phe-hArg-Trp-ß-Ala-D-Cys)-Thr-NHz; SEO ID NO:23
D-Phe-c(Cys-His-D-Phe-Arg-Bip-ß-Ala-D-Cys)-Thr-NHZ; SEO ID NO:25
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-ß-Ala-D-Cys)-Thr-NHz; SEO ID NO:24
D-Phe-c(Cys-His-D-Phe-hArg-Bip-ß-AIa-D-Cys)-Thr-NH2; SEO ID NO:26
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-ß-AIa-D-Cys)-Thr-NHz; SEO ID NO:26
Ac-NIe-c(Asp-D-AIa-His-D-Phe-Arg-Trp-Lys)-NHz; SEO ID NO:28
Ac-NIe-c(Asp-D-Ala-His-D-Phe-Arg-BaI-Lys)-NHz; SEO ID NO:28
Ac-NIe-C(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-OH; SEO ID NO:29
Ac-NIe-c(Cys-D-Abu-His-D-Phe-Arg-Trp-Cys)-NHz; SEO ID NO:30
Ac-NIe-c(Cys-D-Val-His-D-Phe-Arg-Trp-Cys)-NH2; SEO ID NO:30
Ac-NIe-c(Cys-D-IIe-His-D-Phe-Arg-Trp-Cys)-NH2; SEO ID NO:30
Ac-NIe-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-NHz; SEO ID NO:30
Ac-NIe-c(Cys-D-TIe-His-D-Phe-Arg-Trp-Cys)-NHz; SEO ID NO:30
Ac-NIe-C(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-NH2; SEO ID NO:30
Ac-NIe-c(Pen-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; SEO ID NO:31
Ac-NIe-c(Pen-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; SEO ID NO:32
Ac-Leu-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NHz; SEO ID NO:33
Ac-Cha-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NHz; SEO ID NO:33
Ac-IIe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NHz; SEO ID NO:33
Ac-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NHz; SEO ID NO:33
Ac-Val-C(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NHg; SEO ID NO:33
Ac-2-Nal-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NHz; SEO ID NO:33
Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NHz; SEO ID NO:34
Ac-NIe-c(Cys-3-PaI-D-Phe-Arg-Trp-Gaba-Cys)-NHz; SEO ID NO:35
Ac-NIe-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-OH; SEO ID NO:36
Ac-NIe-c(Cys-His-Phe-Arg-D-Trp-Gaba-Cys)-NHz; SEO ID NO:37
AC-NIe-C(Cys-D-AIa-His-D-2-NaI-Arg-Trp-Cys)-NHz; SEO ID NO:16
Ac-NIe-C(Cys-D-Ala-His-D-2-Nal-Arg-2-NaI-Cys)-NHz; SEQ ID NO:16
Ac-NIe-c(Cys-D-Ala-His-D-2-NaI-Arg-BaI-Cys)-NH2; SEQ ID NO:20
Ac-NIe-C(Asp-His-D-2-Nal-Arg-Trp-Ala-Lys)-NHz; SEQ ID NO:38
Ac-NIe-c(Asp-His-D-2-NaI-Arg-Trp-ß-AIa-Lys)-NH2; SEQ ID NO:38
Ac-NIe-c(Cys-His-D-2-NaI-Arg-Trp-Gaba-Cys)-NHz; SEQ ID NO:39
Ac-NIe-c(Cys-His-D-2-NaI-Arg-Trp-Ahx-Cys)-NHz; SEQ ID NO:39
Ac-hPhe-c(Asp-His-D-2-NaI-Arg-Trp-Gaba-Lys)-NHz; SEQ ID NO:40
Ac-Cha-c(Asp-His-D-2-NaI-Arg-Trp-Gaba-Lys)-NH2; SEQ lD NO:40 veya
Ac-Arg-c(Cys-D-Ala-His-D-2-NaI-Arg-Trp-Cys)-NHz; SEQ ID NO:49 veya bunlarin
farmasötik olarak kabul edilen tuzlari.
Burada ayrica, memeli denekte insülin direncini kilo kaybederek veya kilo kaybetmeden,
terapötik etkili miktarda Formül (II) 'ye uygun melanokortin reseptörü Iigandinin ve bunlarin
farmasötik olarak kabul edilen tuzlarinin, hidratlarinin, solvatlarinin veya ön ilaçlarinin
verilmesi yolu ile tedavi etme yöntemi tarif edilmektedir (bkz. Uluslararasi Patent Basvurusu
A1 , Nle veya çikarilmis; A2 , Cys veya Asp;A3 Glu veya D-Ala; A4 ,HisçA5 D-Phe;A6 Arg;A7
Trp, 2-Nal veya Bal; A8 ,Gly, Ala, D-Ala, ß-Ala, Gaba veya Apn; A9 , Cys veya Lys; R2 ve R3'
ün her birisi, H veya (C1-Cs)asil ihtiva eden gruptan bagimsiz olarak seçilmistir; su kosul ile ki
(I). R2 , (C1-Ce)asil ise, bu durumda R3 H 'dir; ve (II). A2 , Cys ise, bu durumda A9 Cys, veya
farmasötik olarak kabul edilen tuzudur.
Memeli denegin, kilo kaybederek veya kilo kaybi olmadan insülin direncinin tedavisinde
yararli olan hemen yukaridaki bilesik grubu örnekleri asagidaki formülün bilesikleridir: Ac-
NIe-c(Cys-D-Ala-His-D-Phe-Arg-Trp-GIy-Cys)-NHz; SEQ ID N0:54AC-NIe-c(Cys-D-Ala-His-
D-Phe-Arg-Trp-D-AIa-Cys)-NHz; SEQ ID NO:54Ac-NIe-c(Cys-D-Ala-His-D-Phe-Arg-Trp-ß-
AIa-Cys)-NH2; SEQ ID NO:54 Ac-NIe-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; SEQ
GIu-His-D-Phe-Arg-Trp-AIa-Cys)-NHz; SEQ ID NO:55Ac-c(Cys-GIu-His-D-Phe-Arg-Z-Nal-
AIa-Cys)-NH2; SEQ ID NO:55Ac-c(Cys-D-Ala-His-D-Phe-Arg-Trp-AIa-Cys)-NHz; SEQ ID
NO:56Ac-c(Cys-D-Ala-His-D-Phe-Arg-Z-Nal-Ala-Cys)-NHz; SEQ lD NO:56Ac-NIe-c(Cys-D-
AIa-His-D-Phe-Arg-Trp-AIa-Cys)-NH2; SEQ ID NO:57Ac-Nle-c(Cys-D-AIa-His-D-Phe-Arg-
Trp-3-AIa-Cys)-NH2; SEQ ID NO:57Ac-NIe-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Gaba-Cys)-NHz;
SEQ ID NO:57 veya Ac-NIe-c(Asp-D-AIa-His-D-Phe-Arg-Bal-AIa-Lys)-NHz; SEQ ID NO:58
veya bunlarin farmasötik olarak kabul edilen tuzu.
Burada ayrica, memeli denekte insülin direncini kilo kaybederek veya kilo kaybetmeden,
terapötik etkili miktarda Formül (III) 'e uygun melanokortin reseptörü bilesiginin ve bunlarin
farmasötik olarak kabul edilen tuzlarinin, hidratlarinin, solvatlarinin veya ön ilaçlarinin
verilmesi yolu ile tedavi etme yöntemi açiklanmaktadir (bkz. Uluslararasi Patent Basvurusu
kismidir; burada, en az 15 amino asit L-Arg, D-Arg, L-hArg veya D-hArg ihtiva eden
gruptan bagimsiz olarak seçilmistir, veya B1 opsiyonel olarak çikarilmistir; A1 , Acc,
HN-(CH2)m-C(O), L- veya D-amino asit veya çikarilmistir; A2 , Cys, D-Cys, hCys, D-
hCys, Pen, D-Pen, Asp veya Glu; A3 , Gly, Glu, Ala, ß-Ala, Gaba, Aib, D-amino asit
veya çikarilmistir; A4 , His, 2-Pal, 3-Pal, 4-Pal, Taz, 2-Thi, 3-Thi veya
(X1,X2,X3,X4,X5)phe; A5 , D-Phe, D-1-Nal, D-2-Nal, D-Trp, D-Bal, D-
(X1,X2,X3,X4,X5)Phe, D-(Et)Tyr, D-Dip, D-Bip veya D-Bpa; A6 , Arg, hArg, Dab, Dap,
Lys, Orn or HN-CH((CH2)n-N(R4R5))-C(O);
A7 , Trp, 1-Nal, 2-Nal, Bal, Bip, Dip, Bpa, D-Trp, D-1-Nal, D-2-Nal, D-Bal, D-Bip, D-Dip
veya D-Bpa;
A8 , Gly, D-Ala, Acc, Ala, ß-Ala, Gaba, Apn, Ahx, Aha, HN-(CH2)5-C(O) veya
çikarilmistir;
A9 , Cys, D-Cys, hCys, D-hCys, Pen, D-Pen, Dab, Dap, Orn veya Lys;
A10 , Acc, HN-(CHz)t-C(O), Pro, hPro, 3-Hyp, 4-Hyp, Thr, L- veya D-amino asit veya
çikarilmistir;
A11 , Pro, hPro, 3-Hyp, 4-Hyp veya çikarilmistir;
A12 , Lys, Dab, Dap, Arg, hArg veya çikarilmistir;
A13 , Asp, Glu veya çikarilmistir;
B2 , 1, 2, 3, 4, veya 5 amino asit ihtiva eden peptid kismidir veya çikarilmistir,
burada, en az 5 amino asit L-Arg, D-Arg, L-hArg ve D-hArg ihtiva eden gruptan
bagimsiz olarak seçilmistir veya çikarilmistir;
R1 ,OH veya NHz'dir;
(Cz-Cao)alkenil, (Cz-Cgo)alkinil, ariI(C1-C30)alkil, ariI(C1-C30)asil, ikameli (C1-C3o)alkil,
ikameli (C1-Cgo)heteroalkil, ikameli (C1-Cao)asil, ikameli (Cz-C30)alkenil, ikameli (CZ-
Cao)alkinil, ikameli aril(C1-C30)alkil ve ikameli aril(Ci-C30)asil ihtiva eden gruptan
bagimsiz olarak seçilmistir;
R4 ve R5 `iri her birisi her vaka için, H, (Ci-C4o)alkil, (Ci-C40)heteroalkil, (Ci-C40)asil,
ikameli (C1-C4o)heteroalkil, ikameli (C1-C4Ü)asil, ikameli (CZ-C40)alkenil, ikameli (Cz-
C(NH)-NH2 ihtiva eden gruptan bagimsiz olarak seçilmistir;
n, bagimsiz olarak her vaka için, 1, 2, 3, 4 veya 5;
m, bagimsiz olarak her vaka için, 1, 2, 3, 4, 5, 6 veya 7;
s, bagimsiz olarak her vaka için, 1, 2, 3, 4, 5, 6 veya 7;
t, bagimsiz olarak her vaka için, 1, 2, 3, 4, 5, 6 veya 7;
X1, X2, X3, X4 ve X5 'in her birisi bagimsiz olarak her vaka için, H, F, ci, Br, i, (C1,
)alkinil, aril, ikameli ariyl, OH, NH2, N02 veya CN ”dir; su kosulla ki:
(I) R4 , (Ci-C40)asil, ariI(C1-C40)asil, ikameli (Ci-C4o)asil, ikameli aril(C1-C4o)asil,
(Ci-C4o)alkilsulf0nil veya C(NH)-NH2 ise, bu durumda R5 H, (C1-C40)alkil, (Ci-
C40)heteroalkil, (C2-C4o)a|kenil, (C2-C4O)alkinil, ariI(C1-C40)alkil, ikameli (Ci-
C40)alkil, ikameli (Ci-C40)heteroalkil, ikameli (Cz-C40)alkenil, ikameli (Cz-
C40)alkinil veya ikameli aril(Ci-C40)alkildir;
(II) R2 , (Ci-C30)asil, ariI(C1-C30)asil, ikameli (C1-C30)asil veya ikameli ariI(Ci-
Cgo)aSII ise, bu durumda R3 H, (C1'Cgo)alkii, (Ci-Cso)heteroalkil, (Cz-Cgo)alkenil,
(Cz-Cso)a|kinil, ariI(C1-C30)alkil, ikameli (C1-C30)alkil, ikameli (C1-C30)heteroalkil,
ikameli (Cz-Cso)alkenil, ikameli (Cz-C30)alkinil veya ikameli ariI(Ci-Cgo)alkildir;
(III) ne B1 ne de 82 asagidaki amino asit dizilerinden bir veya birden fazlasini
ihtiva etmez: Arg-(Lys)2-(Arg)2-Gln-(Arg)3, Tyr-Ala-Arg-Lys-AIa-(Arg)2-GIn-Ala-
Tyr-AIa-Arg-Ala-Pro-(Arg)2-AIa-(Arg)3 or Tyr-AIa-Arg-Ala-Pro-(Arg)2-Pro-(Arg)2;
(IV) B1 ya da 82 veya her ikisi birden söz konusu bilesikte bulunmalidir;
(V) A2 Cys, D-Cys, hCys, D-hCys, Pen veya D-Pen ise, bu durumda A9 Cys,
D-Cys, hCys, D-hCys, Pen veya D-Pen 'din ve
(VI) A2 , Asp veya Glu ise bu durumda A9 Dab, Dap, Orn veya Lys `dir;
veya bunlarin farmasötik olarak kabul edilen tuzlari.
Burada tarif edilen bir uygulama, memeli denekte kilo kaybederek veya kilo kaybi olmaksizin
insülin direncini tedavi etmek için Formül (III) bilesiklerinin kullanilmasidir, burada,
B1 , Arg-Lys-Gln-Lys-(Arg)5, Arg-(Lys)2-Arg-GIn-(Arg)4, Arg-(Lys)2-(Arg)3-GIn-(Arg)2. Arg-
(Lys)2-(Arg)4-GIn-Arg, Arg-(Lys)2-(Arg)5-Gln, Arg-(Lys)2-Gln-(Arg)5, Arg-GIn-(Lys)2-(Arg)5, Arg-
(Arg)e-GIn-(Arg)3. (Arg)7. (Arg)7-GIn-(Arg)2, (Arms. (Arg)s-GIn-Arg, (Arg)9. (Arms-Gm, (D-Arg)5.
(D-Arg)6, (D-Arg)7. (D-Arg)g, (D-Al'g)9, GIn-Arg-(Lys)2-(Arg)5, GIn-(Arg)g, GIn-(Arg)9. Tyr-Gly-
Arg-(Lys)2-(Arg)2-GIn-(Arg)3, Tyr-GIy-Arg-(Lys)2- Arg)2-GIn-(Arg)3-Doc; veya çikarilmistir;
82 , ,B-Ala, ß-AIa-Gly, ß-AIa-Tyr, ß-AIa-Tyr-Gly, (ß-Ala)2, (ß-Ala)2-Gly, (ß-Ala)2-Tyr, (ß-Ala)2-
veya çikarilmistir;
Gln-(Argls. Arg-(LYS)2-(Arg)2-G|n-(Ar4-G|n-
Arg, Arg-(Lys)2-(Arg)5-Gln, Arg-GIn-(Lys)2-(Arg)5, Arg-Gln-(Argb, Arg-Gln-(Arg)s, (Arg)2-Lys-
Arg)5, (D-Arg)7, (D-Arg)8, (D-Arg)9. GIn-Arg-(Lys)2-(Arg)5. GIn-(Arg)g, GIn-(Arg)9 veya
çikarilmistir;
A1 , ABC, Cha, hCha, Chg, D-Chg, hChg, Gaba, hLeu, Met, ß-hMet, D-2-Nal, Nip, Nle, Oic,
Phe, D-Phe, hPhe, hPro veya çikarilmistir;
A2 , Cys 'dir
A3 , D-Abu, Aibi Ala, ß-Ala, D-Ala, D-Cha, Gaba, Glu, Gly, D-Ile, D-Leu, D-Met, D-Nle, D-
Phe, D-Tle, D-Trp, D-Tyr, D-Val veya çikarilmistir;
A4 , His 'dir;
A5 , D-Bal, D-1-Nal, D-2-Nal, D-Phe, D-(X1,X2,X3,X4,X5)Phe, D-Trp, veya D-(Et)Tyr 'dir;
A6 , Arg veya hArg 'dir;
A7 , Bal, Bip, 1-Nal, 2-Nal, Trp, veya D-Trp 'dir;
A8 , A5c, Aöc, Aha, Ahx, Ala. ß-Ala, Apn, Gaba, Gly 'dir, veya çikarilmistir;
A9 , Cys, D-Cys, hCys, D-hCys, Lys, Pen, veya D-Pen 'dir;
A10 ,Pro, Thr 'dir veya çikarilmistir;
A11 , Pro 'dur veya çikarilmistir;
A12 arg, Lys'dir, veya çikarilmistir;
A13 , Asp 'dir veya çikarilmistir;
R2 ve R3 *ün her birisi bagimsiz olarak, H veya asil;
veya bunlarin farmasötik olarak kabul edilen tuzlari.
Memeli denegin, kilo kaybederek veya kilo kaybi olmadan insülin direncinin tedavisinde
yararli olan hemen yukaridaki bilesik gruplarinin Formül (III) 'e uygun Iigand örnekleri
asagidaki formülün bilesikleridir:
Tyr-Gly-Arg-(Lys)2-(Arg)2-GIn-(Arg)3-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-NHz; (SEQIDNO:60)
Tyr-Gly-Arg-(Lys)z-(Arg)2-Gln-(Arg)3-Doc-N1e-C(Asp-His-D-2-Nal-Arg-Trp-Lys)-
NI-Iz; (SEQ ID NO:61)
Nle-C(Asp-His-D-Z-Nal-Arg-Trp-Ly 5)-_13-A1a-Tyr-Gly-Arg-(Lysp-(Arg)2-Gln-(Arg)s-
NHz; (SEQ ID NO:62)
AC-Nle-C(Asp-His-D-Z-Nal-Arg-Trp-Lys)-ß-Ala-Tyr-C1y-Arg-(Lys)2-(Arg)2-Gln-
(Arg)3-NH2; (SEQ ID NO:62)
N Ie-C(Asp-Hi s-D-2-N a I-Arg-Trp- Lys)-(D oc)2-Tyr-GIy-Arg-(Lys)2-(Arg)2-Gln-(Arg)s-
NHi; (SEQ ID NO:63)
AC-Nle-C(Asp-His-D-2-Nal-Arg-Trp-Lys)-(Pro)2-Lys-Asp-Tyr-GIy-Arg-(Lys)2-(Arg)2-
AC-C(Cys-GIu-H is-D-2-Na I-Arg-Trp-Gly-Cys)-(Pro)2-Lys-Asp-Tyr-Gly-Arg-(Lys)2-
(Arg)2-Cln-(Arg)3-NHz; (SEQ ID NO:65)
AC-Nl e-C(As p-His-D-Z-Nal -A rg-Trp-Lys)- ([.l-AI a)2-Tyr-G1y-A rg-(Lys)z-(Arg)2-Gl n-
(Arg)s-NH:; (SEQ 1D NO:66)
AC-Nle-C(Asp-His-D-2-Nal-Arg-Trp-Lys)-(Pr0)2-Lys-Asp-Doc-Tyr-Gly-Arg-(Lys)2-
(Arg)z-Gln-(Arg)3-NH2; (SEQ 1D NO:67)
AC-C(Cys-Glu-His-D-Z-Na]-Arg-Trp-GIy-Cys)-(Pr0)2-Lys-Asp-D0C-Tyr-Gly-Arg-
(Lys)2-(Arg)2-G1n-(Arg)3-NH:; (SEQ ID NO:68)
AC-C(CyS-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro):-Lys-Asp-ß-Ala-Tyr-Gly-Arg-
(Lys)2-(Arg)z-Gln-(Arg)3-NHz; (SEQ ID NO:69)
AC-C(CyS-Clu-His-D-Z-Nal-Arg-Trp-Ala-CyS)-(Pr0)2-Lys-Asp-D0C-Tyr-Cly-Arg-
(Lys)2-(Arg)2-Gl.n-(Arg)3-NH2; (SEQ 1D NO:69)
Ac-Nle-C(Asp-Hîs-D-Z-Na]-Arg-Trp-Lys)-(D0c)z-Tyr-Gly-Arg-(Lys)2-(Arg)2-G1n-
(Arg)3-NI-Ii; (SEQ ID NO:70)
Ac-c(Cys-Glu-His-D-2-N al-Arg-Z-N al-Ala-Cys)-(Pro)2-Lys-Asp-jS-Ala-Tyr-GJy-Arg-
(Lys)2-(Arg)2-Gln-(Arg)3-NI-12; (SEQ ID NO:71)
Ac-C(Cys-GIu-His-D-Z-Nal-Arg-Bal-Ala-Cys)-(Pr0)2-Lys-Asp-_]3-A1a-(Arg)s-Gln-
(Arg)3-Nl-12; (SEQ 1D NO:72)
AC-C(Cys-G1Li-His-D-Z-NaI-Arg-BaI-A]a-Cy5)-(Pr0)2-Lys-Asp-f3`-A]a-GIy-(Arg)s-G1n-
(Arg)3-NI-Iz; (SEQ ID NO:73)
AC*C(CySýGluýHisýDIZINalýArgIBalýAlaýCyS)I(Pr0)2ýLysýAspýßýAlaýTyrýGlyý(Arg)sý
AC-C(Cys-Glu-His-D-2-N al-Arg-Trp-Ala-Cys)-(Pro)--Lys-Asp-ß-Ala-Tyr-Gly-Arg-
(Lys)2-Arg-G1n-(Arg)4-NH2; (SEQ ID NO:75)
Ac-c(Cys-GJu-His-D-2-Nal-Arg-Trp-AJa-Cys)-(Pr0)2-Lys-Asp-j3-Ala-Tyr-Gly-Arg-
(Lys)2-G1n-(Arg)s-NH2; (SEQ ID NO:76)
AC-C(CyS-G1 LI -Hi s-D-Z-Nal -A rg-Trp-A] a-Cys)-(P r0)2-LyS-ASp-ß-Ala-Ty r-GIy-A rg-
Lys-Gln-Lys-(Arg)5-NI-Iz; (SEQ ID NO:77)
AC-C(CyS-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pr0)2-Lys-Asp-ß-Ala-Tyr-Gly-Arg-
(Lys)2-(Arg)4-G]n-Arg-NHQ; (SEQ TD NO:78)
AC-C(CyS-G1u-Hîs-D-Z-NaI-Arg-Ba]-Ala-Cys)-(Pr0)2-Lys-Asp-ß-Ala-Tyr-Aib-Arg-
(Lys)2-(Arg)2-GIn-(Arg)3-NH2; (SEQ ID NO:79)
AC-C(Cys-G1Li-His-D-Z-Nal-Arg-l-Nal-Ala-Cys)-(Pr0)2-Arg-Asp-ß-Ala-(Arg)s-Gln-
(Arg)3-Nl-lz; (SEQ ID NO:80)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-l -N al-Ala-Cys)-(Pr0):-Lys-Asp-ß-Ala-(Arg)s-Gln-
(Arg)3-NI-Ii; (SEQ ID NO:80)
Ac-C(Cys-GIu-HiS-D-Z-Nal-Arg-î -Nal-A] a-Cys)-(Pro)2-Lys-Asp-ß-A] a-(Arg)a-G]n-
(Arg)3-NHz; (SEQ 1D NO:81)
AC-C(Cys-Clu-His-D-2-N al-Arg-Z-N al-Ala-Cys)-(Pro)2-Ar g-Asp-ß-Ala-(Ar g)s-Cln-
(Arg)3-NH2; (SEQ ID NO:82)
AC-C(Cys-GIu-His-D-Z-NaI-Arg-Z-Na]-Ala-Cys)-(Pr0)2-Lys-Asp-ß-Ala~(Arg)s-G]n-
(Arg)3-Nl-lz; (SEQ 1D NO:82)
AC-C(Cys-Glu-His-D-Z-Nal-Arg-Z-Nal-Ala-Cys)-(Pr0)2-Lys-Asp-f3-Ala-(Arg)e-Gln-
(Arg)3-NI-Iz; (SEQ ID NO:81)
AC-C(Cys-Gîu -Hi' s-D-Z-Nal-Arg-BaI-Ala -Cys)-(Pr0)2-Arg-Asp-ß-AI a -(Arg)e-Gh'i-
(Arg)3-NH:; (SEQ ID NO:83)
Ac-c(Cys-Glu-His-D-2-N al-Arg-Bal-Ala-Cys)-(Pr0)2-Arg-Asp-ß-Ala-(Arg)5-Gln-
(Arg)3-NI-Iz; (SEQ ID NO:84)
AC-C(CyS-Clu-HiS-D-Z-Nal-Arg-Bal-Ala-Cys)-(Pr0)2-Lys-Asp-ß-Ala-(Arg)is-Cln-
(Arg)3-NH2; (SEQ ID NO:83)
AC-C(CyS-G1 LI -Hi s-D-Z-Na 1 -A rg-Trp-A] a-Cys)-(P r0)i-Lys-As p-ß-AIa-Ty r-GIy-A rg-
(Lys)2-(Arg)3-Gln-(Arg)z-NH2; (SEQ 1D NO:85)
AC-C(Cys-Clu-HIs-D-Z-Nal-Arg-Trp-Ala-Cys)-(Pr0)2-Lys-Asp-ß-Ala-Tyr-Cly-Arg-
G]n-(Lys)2-(Arg)s-NH2; (SEQ ID NO:86)
AC-C(Cys-G1u -Hi' s-D-Z-Nal -Arg~Trp-A] a-Cys)-(Pr0)2-Lys-Asp-ß-AIa-Tyr-GIy-Arg-
(Lys)2-(Arg)s-Gln-Nl-lz; (SEQ 1D NO:87)
ACIC(CysýG1LiýHisýDIZINalýArgýl*NalýAlaýCys)ý(Pr0)2ýLys*AspîßýAlaýTyrýGlyýArg*
(Lys)2-(Arg)2-Gh1-(Arg)3-NI-12; (SEQ ID NO:71)
Ac-c(Cys-Glu-His-D-2-N al-Arg-BaJ-Ala-Cys)-(Pr0)2-Lys-Asp-ß-Ala-Tyr-Gly-Arg-
(Lys)2-(Arg)2-Gln-(Arg)3-NI-12; (SEQ ID NO:71)
Ac-C(Cys-G1u-His-D-Z-Na]-Arg-î -NaI-A]a-Cys)-(Pr0)2-Lys-Asp-ß-A1a- (Arg)2-Lys-
(Arg)2-Gln-(Arg)3-NHz; (SEQ ID NO:88)
AC-C(Cys-Glu-His-D-2-N aJ-Arg-l -N al-Ala-Cys)-(Pr0):-Lys-Asp-ß-Ala-Arg-Lys-
(Arg)3-G1n-(Arg)3-NH2; (SEQ TD NO:89)
AC-C(Cys-G1Li-His~D~2-Nal-Arg-2-Nal-A] a-Cys)-(Pr0)2~Lys-Asp-ß-A1a- (Arg)2-Lys-
(Arg)z-Gln-(Arg)3-NI-Iz; (SEQ ID NO:88)
AC-C(Cys-Glu-His-D-2-Nal-Arg-Z-Nal-Ala-Cys)-(Pro)2-Lys-Asp-ß-Ala-Tyr-Gly-(Arg)2-
Lys-(Arg)z-Gln-(Arg)s-N
AC-C(Cys-C1u-Hi's-D-Z-NaI-Arg-Z-NaI-Ala-Cys)-(Pr0)2-Lys-Asp-ß-AIa-GIy-(Arg)2-Lys-
(Arg)z-Gln-(Arg)3-NI-Iz; (SEQ ID NO:91)
Ac-c(Cys-Glu-His-D-2-N al-Arg-Z-N al-Ala-Cys)-(Pr0)2-Lys-Asp-ß-Ala-Gly-Arg-Lys-
(Arg)3-Gln-(Arg)s-NHz; (SEQ ID NO:92)
AC-C(CyS-Clu-Hîs-D-Z-Nal-Arg-l-Nal-Ala-Cys)-(Pr0)2-Lys-Asp-ß-Ala- (Arg)2-L.ys-
(Arg)z-G1n-(Arg)3-NH2; (SEQ ID NO:93)
AC-C(Cys-GIu-H is-D-Z-Nal-Arg-î -Nal -AIa-Cys)-(Pr0)2-Lys-Asp-ß-Ala -Arg-Lys-
(Arg)3-Gln-(Arg)3-NHz; (SEQ 1D NO:94)
ACIC(CySIGluýHiSIDIZINalýArgýl*NalýAlaICys)I(Pr0)2*LysýAspýjîýAlaýTyrýGlyý(Arg)2ý
Lys-(Arg)2-G1n-(Arg)3-NH2; (SEQ TD NO:95)
Ac-C(Cys-G1u-Hi' s-D-Z-NaI-Arb-'l -Nal -AI a-Cys)-(Pr0)2-Lys-Asp-j3-Al a-Ty r-Gly-Arg-
Lys-(Arg)3-Cln-(Arg)3-NI-Iz; (SEQ ID NO:96)
AC-C(Cys-G1Li-His-D-2-Nal-Arg-l-Nal-Ala-Cys)-(Pr0)2-Lys-Asp-ß-Ala-Gly-(Arg)2-Lys-
(Arg)2-Gln-(Arg)3-N
Ac-c(Cys-Glu-His-D-2-N al-Arg-l-N aJ-Ala-Cys)-(Pr0)2-Lys-Asp-ß-Ala-Gly-Arg-Lys-
(Arg)3-Gln-(Arg)s-NHz; (SEQ ID NO:92)
Ac-C(Cys-Glu-His-D-Z-Nal-Arg-Z-Nal-Ala-Cys)-(Pr0)z-Lys-Asp-ß-A]a-(A rg)2-Lys-
(Arg)2-Gln-(Arg)3-NH:; (SEQ ID NO:98)
AC-C(Cys-Clu-His-D-2-N al-Arg-Z-N al-Ala-Cys)-(Pr0)2-Lys-Asp-ß-Ala-Arg-Lys-
(Arg)3-G1n-(Arg)3-NH2; (SEQ TD NO:99)
AC-C(CyS-G] u -Hi S-D-Z-Na] -A rg-Z-Nal -Al a-Cys)-(Pro)z-Lys-Asp-ß-A1 a -Ty r-GI y-(A r g):-
Lys-(Arg)z-Gln-(Arg)3-N
AC-C(Cys-Glu-His-D-2-N al-Arg-Z-N al-Ala-Cys)-(Pr0).-Lys-Asp-_ß-Ala-Tyr-Gly-Arg-
Lys-(Arg)3-Gln-(Arg)s-NI-Iz; (SEQ ID No:101)
AC-C(Cys-G1u-Hi' s-D-Z-NaI-Arg-Z-Nal -Al a-Cys)-(Pr0)2-Lys-Asp-_/3-AI a-GIy-(Arg)2-Lys-
(Arg)2-G1n-(Arg)s-NI-Iz; (SEQ ID No:102)
Ac-c(Cys-Glu-His-D-2-N al-Arg-Z-N aJ-Ala-Cys)-(Pr0)2-Lys-Asp-ß-Ala-Gly-Arg-Lys-
(Arg)3-Gln-(Arg)s-NH:; (SEQ ID No:103)
AC-C(CyS-Glu-His-D-Z-Nal-Arg-Bal-Ala-CyS)-(Pr0)2-LyS-ASp-ß-Ala- (Arg)1-Ly5-
(Arg)2-G1n-(Arg);-NH2; (SEQ ID No:104)
AC-C(Cys-G1Li-His-D-Z-Na]-Arg-BaI-AIa-Cys)-(Pr0)2-Lys-Asp-ß-A1a-Arg-Lys-(Arg)3-
Ghi-(Arg)3-NHz; (SEQ ID No:105)
ACIC(CysýGluýHisýDIZINalýArgIBalýAlaýCys)ý(Pr0)2ýLysýAspýßýAlaýTyrýGly*(Arg)2ý
Lys-(Arg)2-GIn-(Arg)s-NH2; (SEQ ID No:100)
AC-C(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pr0)2-Lys-Asp-ß-A1a-Tyr-GIy-Arg-Lys-
(Arg)3-Gln-(Arg)s-NH2; (SEQ ID No:101)
AC-C(Cys-Glu-His-D-Z-Nal-Arg-Bal-Ala-Cys)-(Pr0)2-Lys-Asp-ß-Ala-Gly-(Arg)2-Lys-
(Arg)2-Gln-(Arg)3-NHz; (SEQ 1D No:102)
Ac-c(Cys-Glu-His-D-2-N al-Arg-BaJ-Ala-Cys)-(Pro)2-Lys-Asp-ß-Ala-Gly-Arg-Lys-
(Arg)3-Gln-(Arg)i-N Hz; (SEQ ID No:103)
Ac-C(CyS-G1u -Hi s-D-Z-Nal -A rg-Trp-A] a-Cys)-(Pro):-Lys-Aspj3-AIa-Ty r-GIy-A rg-
(Lys)2-Arg-Cln-(Arg)4-NI-12; (SEQ ID No:106)
AC-C(Cys-GJu-His-D-2-Nal-Arg-Trp-AJa-Cys)-(Pr0)2-Lys-Asp-j3-AJa-Tyr-Gly-Arg-
(Lys)2-G1n-(Arg)s-NH2; (SEQ ID No:107)
AC-C(Cys-G1 Li-His-D-2~Nal~Arg-Trp~A1a-Cys)~(Pr0)2-Lys~Asp-_/3~Ala~Ty r-Gly-Arg-
Lys-Ch1-Lys-(Arg)s-NI-Iz; (SEQ ID No:108)
Ac-c(Cys-GlLi-His-D-Z-Nall-Arg-Trp-Ala-Cys)-(Pr0)i-Lys-Asp-ß-Ala-Tyr-Gly-Arg-
Gln-(Lys)2-(Arg)s-NI-12; (SEQ 1D No:109)
AC-C(Cys-C1u -Hi' s-D-Z-Nal-Arg-Trp-A] a-Cys)-(Pr0)i-Lys-Asp-ß-Ala-Tyr-Gly-Arg-
(Lys)2-(Arg)3-Cln-(Arg)z-NI-Iz,^ (SEQ ID No:110)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-AJa-Cys)-(Pr0);Lys-Asp-ß-Ala-Tyr-Gly-Arg-
(Lys)2-(Arg)4-Gln-Arg-NI-Ii; (SEQ ID No:111)
AC-C(CyS-Clu-His-D-2-N al-Arg-Trp-Ala-Cys)-(Pr0)2-Lys-Asp-ß-Ala-Tyr-Cly-Arg-
(Lys)2-(Arg)a-GIn-NH2; (SEQ ID No:112)
AC-C(Cys-G1Li-His-D-Z-Na]-Arg-Trp-A] a-Cys)-(Pr0)2-Lys-Asp-ß-A1a-(Arg).=-Gl'n-
(Arg)3-NH2; (SEQ 1D N 0113)
AC-C(Cys-Clu-His-D-Z-Nal-Arg-Trp-Ala-Cys)-(Pr0)2-Arg-ASp-ß-Ala-(Argß-Cln-
(Arg)3-NH2; (SEQ ID No:1 13)
Ac-C(Cys-Glu-Hi's-D-Z-Nal-Arg-Trp-AIa-Cys)-(Pr0)2-Lys-Asp-ß-A]a-Tyr-Gly-(Argß-
Gln-(Arg)3-NH:; (SEQ ID No:114)
Acýc(CysýGlLiýI-IisýDý2ýNalýArgýTrpýAlaICys)ý(Pro)2*Arg*AspýßýAlaýTyrýGlyýmrgký
Gln-(Arg)3-NI-Iz; (SEQ ID NO:114)
Ac-c(Cys-Glu-His-D-2-N al-Arg-Trp-Ala-Cys)-(Pr0)z-Lys-Asp-ß-Ala-(Arg)s-Gln-
(Arg)4-NI-Iz; (SEQ ID No:115)
Ac-C(Cys-Glu-His-D-Z-Na]-Arg-Trp-AIa-Cys)-(Pr0)2-Arg-ASp-ß-A]a-(Arg).=,-GIn-
(Arg)4-NI-Iz; (SEQ ID No:115)
Ac-c(Cys-Glu-Hîs-D-2-Nal-Arg-Trp-Ala-Cys)-(Pr0)2-Lys-Asp-jS-Ala-Tyr-Gly-(Arg)s-
G]n-(Arg)4-NH2; (SEQ ID No:116)
AC-C(Cys-G1Li-His-D-Z-NaI~A rg-Trp-A]a-Cys)-(Pro)2-Arg-Asp-ß-AIa-Tyr-Gly-(Arg)s-
GJn-(Argp-Nl-h; (SEQ 1D No:116)
AC-C(Cys-Glu-His-D-Z-Nal-Arg-l-Nal-Ala-Cys)-(Pr0)2-Lys-Asp-f3-Ala-(Arg)s-Gln-
(Arg)3-NI-Iz; (SEQ ID No:117)
AC-C(Cys-G1u-His-D-2-NaI-Arg-1-Nal-Ala-Cys)-(Pr0)z-Arg-Asp-_ß-A]a-(Arg)s-Gln-
(Arg)3-NHi; (SEQ ID No:117)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-l-N al-Ala-Cys)-(Pr0)2-Lys-Asp-ß-Ala-(Arg)s-Gln-
(Arg).i-NI-Ii; (SEQ ID No:1 18)
AC-C(CyS-Glu-HIS-D-2-N al-Arg-l-N al-Ala-CyS)-(Pro)2-Arg-ASp-ß-Ala-(Arg)5-Gln-
(Arg)i-NH2,' (SEQ ID No:118)
AC-C(Cys-GIu-His-D-2-NaI-Arg-1-Nal-A]a-Cys)-(Pro)2-Lys-Asp-ß-A]a-(Arg)e-G]n-
(Arg)3-NHz; (SEQ ID No:119)
AC*C(Cys*GluýHISIDIZINalýArgII*NalýAlaýCys)ý(Pro)2ýArgýAspýßýAlaý(Arg)sýGlný
(Arg)3-NH2; (SEQ ID No:119)
Ac-C(Cys-G1u-Hi's-D-Z-Nal-Arg-î -Nal-A]a-Cys)-(Pr0)2-Lys-Asp-ß-Ala-Tyr-Gly-(Arg)s-
Gln-(Arg)a-NH:; (SEQ ID No:120)
AC-C(Cys-Glu-His-D-Z-Nal-Arg-l-Nal-Ala-Cys)-(Pr0)2-Arg-Asp-ß-Ala-Tyr-ciy-
(Arg)5-Gln-(Arg)3-NH2; (SEQ 1D N 02120)
Ac-c(Cys-Glu-His-D-2-N al-Arg-l -N al-Ala-Cys)-(Pr0)2-Lys-Asp-ß-Ala-Tyr-Gly-(Arg)5-
Gln-(Arg)4-NH:; (SEQ ID No:121)
AC-C(CyS-GI u -HiS-D-Z-Nal-Arg-î -Nal -Al a-Cys)-(P r0)2-A rg-Asp-ß-AI a -Tyr-Gly-
(Arg)5-Gln-(Arg)4-N Hz; (SEQ 1D NO: 121)
AC-C(Cys-Clu-His-D-2-N al-Arg-l-Nal-Ala-Cys)-(Pr0)2-Lys-Asp-ß-Ala-Tyr-Cly-(Arg)a-
G]n-(Arg)3-NH2; (SEQ ID NO:122)
AC-C(Cys-Glu-H iS-D-Z-Nal-Arg-î -Nal -Al a-Cys)-(P r0)2-A rg-Asp-ß-AIa-Tyr-Gly-
(Arg)s-Gln-(Arg)3-NH2; (SEQ ID No:122)
AC-C(Cys-Glu-His-D-Z-Nal-Arg-Z-Nal-Ala-Cys)-(Pr0)2-Lys-Asp-f3-Ala-(Arg)s-Gln-
(Arg)3-NI-Iz; (SEQ ID No:123)
AC-C(Cys-G1u-His-D-2-NaI-Arg-2-Na1-Ala-Cys)-(Pr0)z-Arg-Asp-_ß-A]a-(Arg)s-Gln-
(Arg)3-NH:; (SEQ ID No:123)
Ac-c(Cys-Glu-His-D-Z-Nal-Arg-Z-N al-Ala-Cys)-(Pr0):-Lys-Asp-ß-Ala-(Arge-Gin-
(Arg)3-NI-Ii; (SEQ ID No:124)
AC-C(CyS-Clu-HIS-D-2-N al-Arg-Z-N al-Ala-Cys)-(Pro)2-Arg-Asp-ß-Ala-(Arg)a-Cln-
(Arg)3-NH2,' (SEQ ID No:124)
AC-C(Cys-GIu-HiS-D-Z-NaI-Arg-Z-Na]-Ala-Cys)-(Pro)2-Lys-Asp-ß-A]a-(Arg).=-C]n-
(Arg)4-Nl-lz; (SEQ 1D No:125)
AC-C(Cys-Clu-HIs-D-Z-Nal-Arb-Z-Nal-Ala-Cys)-(Pro)2-Arg-Asp-ß-Ala-(Arg)5-Cln-
(Arg)4-NH2; (SEQ ID No:125)
Ac-C(Cys-G1u-His-D-Z-Nal-Arg-Z-Nal-Ala-Cys)-(Pr0)2-Lys-Asp-ß-A1a-Tyr-G]y-(Arg)s-
Gln-(Arg)3-NHi; (SEQ 1D No:126)
ACIC(CysýGlu*HisýDIZINalýArgIZINalýAlaICys)I(Pr0)2ýArgýAspî13ýAlaýTyrýGlyý
(Arg)5-G1n-(Arg)3-NI-Iz; (SEQ ID NO:126)
Ac-c(Cys-Glu-His-D-2-N al-Arg-Z-Nal-Ala-Cys)-(Pr0)2-Lys-Asp-ß-Ala-Tyr-Cly-(Arg)a-
Gln-(Arg)3-NI-Iz; (SEQ ID No:127)
AC-C(Cys-GIu-HiS-D-Z-Nal-Arg-Z-Na]-Ala-Cys)-(Pr0)2-Arg-Asp-ß-AIa-Tyr-Gly-
(Arg)e-Gln-(Arg)3-NHZ; (SEQ ID No:127)
AC-C(Cys-Glu-His-D-2-N al-Arg-Z-Nal-Ala-Cys)-(Pr0)2-Lys-Asp-ß-Ala-Tyr-Gly-(Argb-
G]n-(Arg)4-NH2; (SEQ ID No:128)
AC-C(Cys~GIu-His-D~2~Nal-Arg-2~Nal~A1a~Cys)-(Pr0)2-Arg~Asp~ß~AIa~Tyr-Gly~
(Arg)s-Gln-(Arg)s-NH:; (SEQ ID No:128)
AC-C(Cys-Glu-l-lis-D-Z-Nal-Arg-Bal-Ala-Cys)-(Pr0)2-Lys-Asp713-Alai-(Arg)s-Gln-
(Arg)3-NI-Iz; (SEQ 1D No:129)
AC-C(Cys-G1u -Hi' s-D-Z-Nal-Arg-BaI-Ala -Cys)-(Pr0)2-Arg-Asp-ß-AI a-(Arg).=,-Gln-
(Arg)3-NH:; (SEQ ID No:129)
Ac-c(Cys-Glu-His-D-Z-Nal-Arg-Bal-AJa-Cys)-(Pr0)2-Lys-Asp7ß-Ala-(Arg)s-Gln-
(Arg)4-NI-Ii; (SEQ ID No:130)
AC-C(CyS-Clu-His-D-2-N al-Arg-Bal-Ala-Cys)-(Pr0)2-Arg-Asp-ß-Ala-(Arg)s-Cl.n-
(Arg)4-NH2,' (SEQ ID No:130)
AC-C(Cys-GI u-Hi s-D-Z-Na] -A r g-BaI-A] a-Cys)-(Pr0)2-Lys-Asp713-A1 a-(A r g)n-GI n-
(Arg)3-Nl-lz; (SEQ 1D No:131)
ACIC(CysýGlu*HISID*ZINal*ArgýBalýAlaICysy(Pr0)2ýArgýAspýßýAlaý(Arg)sýGlný
(Arg)3-NH2; (SEQ ID No:131)
Ac-C(Cys-G1u -Hi's-D-Z-NaI-Arg-BaI-Ala-Cys)-(Pr0)2-Lys-Asp-ß-A1a-Gly-(Arg)s-G1n-
(Arg)3-NH:; (SEQ ID No:132)
Ac-c(Cys-Glu-His-D-Z-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-_ß-Ala-Tyr-Gly-(Arg)s-
Gln-(Arg)3-Nl-12; (SEQ 1D No:133)
Ac-c(Cys-Glu-His-D-2-N al-Arg-Bal-Ala-Cys)~(Pr0)2-Arg-Asp-ß-Ala-Tyr-Gly-(Arg)s-
Gln-(Arg)3-NHz; (SEQ ID NO:133)
AC-C(CyS-Glu-HiS-D-Z-Nal-Arg-Ba]-AIa-Cys)-(Pr0)2-Lys-A5p-j3-AIa-Tyr-GIy-(Arg)s-
Gln-(Arg)4-NH2; (SEQ 1D NO:134)
Ac-c(Cys-Clu-His-D-2-N al-Arg-Bal-Ala-Cys)-(Pro)2-Arg-Asp-ß-Ala-Tyr-Gly-(Arg)s-
G]n-(Arg)4-NH2; (SEQ ID No:134)
AC-C(Cys-GIu-His-D-Z-Nal-Arg-Ba]-Ala~Cys)-(Pr0)2-Lys-Asp~ß-AIa-Tyr-GIy-(Arg)e-
G]n-(Arg)3-NH2; (SEQ ID NO:135)
Ac-c(Cys-GlLi-l-lis-D-Z-Nal-Arg-Bal-Ala-Cys)-(Pr0)2-Arg-Aspjî-Ala-Tyr-Gly-(Argß-
Gln-(Arg)3-NI-Iz; (SEQ ID NO:135)
AC-N]e-C(Cys-D-A1a-Hîs-D-Phe-Arg-Trp-Cys)-(D0c)2-Tyr-Gly-Arg-(Lys)2-(Arg)z-G1n-
(Arg)3-NH:; (SEQ ID No:136)
Ac-N Ie-c(Cys-D-A]a-His-D-Phe-Arg-Trp-Cysij-Al a-Tyr-Gly-Arg-(Lys)2-Arg-Gln-
(Arg)4-NH2; (SEQ ID No:137)
AC-Nle-C(Cys-D-Ala-His-D-Phe-Arg-Trp-Cy5)-D0C-Tyr-Gly-Arg-(Lys)z-(Arg)2-Gln-
(Arg)3-NH2,' (SEQ ID N01] 36)
Ac-Nle-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-ß-Ala-(Arg)5-GIn-(Arg)3-NHz; (SEQ ID No:138)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-ß-Ala-Gly-(Arg)5-Gln-(Arg)3-NH2; (SEQ ID No:138)
Ac-Nle-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-ß-Ala-GIy-(Arg)5-Gln-(Arg)3-NH2; (SEO ID No:138)
Ac-Nle-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-ß-Ala-Tyr-Gly-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:139)
Ac-N le-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-js`-AJa-Tyr-Gly-(Arg)2-Lys-(Arg)2-Gln-
(Arg)3-NH2; (SEQ ID No:141)
AC-N le-C(Cys-D-A1a-His-D-Phe-Arg-Trp-Cys)-ß-Ala-Tyr-Gly-Arg-Lys-(Arg)3-Gln-
(Arg)s-NH2; (SEQ ID No:142)
AC-NIe-C(Cys-D-A]a-His-D-Phe-Arg-Trp-Cys)-ß-AIa-Gly-(Arg)2-Lys-(Arg)2-Gln-
(Arg)3-NI-Iz; (SEQ ID No:141)
AC-NIe-c(Cys-D~AJa-His-D-Phe-Arg-Trp-Cys)~ß-AIa-GIy-Arg-Lys-(Arg)s-Gln-(Arg)s-
NI-b; (SEQ ID NO:142)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cy5)-j3-A1a- (Arg)2-Lys-(Arg)2-Gln-(Arg)3-
NHz; (SEQ lD No:143)
AC-Nle-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-ß-Ala-Arg-Lys-(Arg)3-GIn-(Arg)3-NHz; (SEO ID No:144)
ACINI eIC(CysýDýA1aýHisýDýPheýArgýTrpýCysyßýA] a*TyrýGlyýArgý(Lys)2ýArgýGIn*
(Arg).i-NHz; (SEQ ID No:145)
AC-Nle-C(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-Arg-(Lys)2-(Arg)2-G]n-
(Am-Nm; (SEQ ID No:146)
Ac-Nle-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-,ß-Ala-(Arg)5-GIn-(Arg)3-NHz; (SEO ID No:148)
AC-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-ß-Ala-GIy-(Arg)5-Gln-(Arg)3-NH2; (SEO ID NO:14?)
Ac-Nle-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-ß-AIa-Tyr-Gly-(Arg)5-GIn-(Arg)3-NHz; (SEO ID NO:14?)
Ac-Nle-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-(ß-Ala)2-(Arg)5-Gln-(Arg)3-NH2; (SEO ID No:148)
Ac-Nle-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-(ß-Ala)2-GIy-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:149)
AC-Nle-C(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(ß-A1a)2-Tyr-Gly-(Arg)5-G1n-(Arg)a-
NHz; (SEQ ID No:149)
Ac-Nle-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-D0c-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:151)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-GIy-(Arg)5-G|n-(Arg)3-NH2; (SEO ID No:150)
AC-Nle-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-GIy-(Arg)5-Gln-(Arg)3-NH2; (SEO ID No:150)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2; (SEO ID No:151)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-GIy-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:152)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(D0c)2-Tyr-Gly-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:152)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-ß-Ala-(Arg)5-Gln-(Arg)4-NHz; (SEO ID No:154)
Ac-Nle-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-ß-Ala-GIy-(Arg)5-G|n-(Arg)4-NH2; (SEO ID No:153)
Ac-Nle-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-ß-Ala-Tyr-Gly-(Arg)5-GIn-(Arg)4-NHz; (SEO ID No:153)
Ac-Nle-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-(ß-Ala)2-(Arg)5-GIn-(Arg)4-NH2; (SEO ID NO: 154)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(ß-Ala)2-GIy-(Arg)s-GIn-(Arg)4-NH2; (SEO ID No:155)
ACEN]eýc(CysýDýA]aýHiSEDEPheýArgETrPECy3)*(I3EA1a)2*TyrýG1yý(Arg)sýG1ri*(Arg)4ý
NHz; (SEQ ID No:155)
Ac-Nle-C(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-D0c-(Arg)5-GIn-(Arg)4-NH2; (SEO ID NO:15?)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-GIy-(Arg)5-Gln-(Arg)4-NH2; (SEO ID No:156)
Ac-Nle-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-GIy-(Arg)s-Gln-(Arg)4-NH2; (SEO ID No:156)
Ac-Nle-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-GIn-(Arg)4-NH2; (SEO ID NO:15?)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-GIy-(Arg)5-GIn-(Arg)4-NH2; (SEO ID No:158)
Ac-Nle-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (SEO ID No:158)
AC-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-ß-AIa-Tyr-Gly-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:159)
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-ß-AIa-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:160)
Ac-Nle-C(Asp-His-D-Phe-Arg-Trp-AIa-Lys)-ß-AIa-Tyr-Gly-(Arg)5-GIn-(Arg)3-NHz; (SEO ID No:161)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-AIa-Lys)-ß-AIa-(Arg)5-GIn-(Arg)3-NHz; (SEO ID No:162)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-ß-Ala-Tyr-GIy-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:164)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-ß-Ala-GIy-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:163)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-ß-Ala-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:163)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(ß-Ala)2-Tyr-GIy-(Arg)5-GIn-(Arg)3-NHz; (SEO ID No:164)
AC-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(,B-Ala)2-Gly-(Arg)5-Gln-(Arg)3-NH2; (SEO ID No:165)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(ß-Ala)2-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:165)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-Tyr-GIy-(Arg)5-Gln-(Arg)3-NHz; (SEO ID No:166)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-D0c-Gly-(Arg)5-Gln-(Arg)3-NH2; (SEO ID No:166)
AC-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-(Arg)5-Gln-(Arg)3-NH2; (SEO ID No:168)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-Tyr-GIy-(Arg)5-GIn-(Arg)3-NH2; (SEO ID NO:16?)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-GIy-(Arg)5-Gln-(Arg)3-NH2; (SEO lD NO:16?)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:168)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-ß-Ala-Tyr-GIy-(Arg)5-GIn-(Arg)4-NHz; (SEO ID No:170)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-ß-Ala-GIy-(Arg)5-GIn-(Arg)4-NHz; (SEO ID No:169)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-ß-Ala-(Arg)5-GIn-(Arg)4-NHz; (SEO ID No:169)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(ß-Ala)2-Tyr-GIy-(Arg)5-GIn-(Arg)4-NH2; (SEO ID No:170)
AC-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(ß-Ala)2-GIy-(Arg)5-Gln-(Arg)4-NH2; (SEO ID No:171)
AC-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(ß-Ala)2-(Arg)5-GIn-(Arg)4-NH2; (SEO ID No:171)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-Tyr-GIy-(Arg)5-GIn-(Ar
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-Gly-(Arg)5-Gln-(Arg)4-NH2; (SEO ID No:172)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-(Arg)5-Gln-(Arg)4-NH2; (SEO ID No:172)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-Tyr-GIy-(Arg)5-GIn-(Arg)4-NH2; (SEO ID No:173)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-GIy-(Arg)5-Gln-(Arg)4-NH2; (SEO lD No:174)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-(Arg)s-G|n-(Arg)4-NH2; (SEO ID No:174)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-ß-AIa-Lys)-ß-AIa-Tyr-Gly-(Arg)5-GIn-(Ai'g)3-NH2; (SEO ID No:175)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-ß-AIa-Lys)-ß-AIa-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:176)
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-ß-Ala-Tyr-GIy-(Arg)5-GIn-(Arg)3-NH2; (SEO ID NO:17?)
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-ß-AIa-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:178)
DIPheIC(CysýHîSIDIPheýArgýTrpýßýA]aýDIC)IS)IThrýßýAIa*TyrýGIyý(Arg)vG1riý(Arg)sý
NH2; (SEQ ID No:179)
D-Phe-c(Cys-His-D-Phe-Arg-Trp-ß-Ala-D-Cys)-Thr-ß-AIa-(Arg)5-Gln-(Arg)3-NHz; (SEO ID No:180)
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-ß-AIa-Tyr-GIy-(Arg)5-GIn-(Arg)3-NHz; (SEO ID No:181)
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-ß-AIa-(Arg)5-GIn-(Arg)3-NHz; (SEO ID No:182)
Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-ß-AIa-Tyr-GIy-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:183)
Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-ß-Ala-(Arg)s-GIn-(Ar
AC-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-ß-AIa-Tyr-GIy-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:183)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-ß-Ala-(Arg)5-Gln-(Arg)3-NH2; (SEO ID No:185)
Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-ß-Ala-Tyr-GIy-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:186)
AC-Chg-C(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-ß-AIa-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:185)
AcýhChaIC(AspýHisýDýPheýArgýTrpýGabaýLys)ý_ßýA1a*TyrýGIy*(Arg)sýG]ný(Arg)sý
NH2; (SEQ ID No:186)
Ac-hCha-C(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-ß-Ala-(Arg)5-G|n-(Arg)3-NH2: (SEO lD No:188)
AC-hCha-C(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(jî-A1a)2-Tyr-Cly-(Arg)5-Gln-(Arg)3-
NHz; (SEQ ID No:187)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(ß-Ala)2-(Arg)5-Gln-(Arg)3-NH2; (SEO ID No:188)
Ac-hCha-C(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-D0c-Tyr-GIy-(Arg)5-Gln-(Arg)3-NH2; (SEO ID No:189)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-D0c-(Arg)5-Gln-(Arg)3-NH2; (SEO lD No:190)
AC-hCha-C(Asp-His-D-Phe-Arg-Trp-Caba-Lys)-(D0C)2-Tyr-GIy-(Arg).=-CIn-(Arg)s-
NHz; (SEQ ID No:189)
Ac-hCha-C(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(Doc)2-(Arg)5-Gln-(Arg)3-NHz; (SEO ID No:190)
AC-hCha-C(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-_ß-A1a-Tyr-Gly-(Arg)s-G]n-(Arg)4-
NHz; (SEQ ID No:191)
Ac-hCha-C(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-ß-Ala-(Arg)5-Gln-(Arg)4-NH2; (SEO ID No:192)
AC-hCha-C(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(j$-Ala)2-Tyr-Gly-(Argb-Gln-(Argh-
NHL' (SEQ ID No:191)
Ac-hCha-C(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(ß-Ala)2-(Arg)5-Gln-(Arg)4-NH2; (SEO ID No:192)
AC-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (SEO ID No:193)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-D0c-(Arg)5-Gln-(Arg)4-NH2; (SEO lD No:194)
AC-hCha-C(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(Doc)2-Tyr-Gly-(Arg)s-G1n-(Arg)4-
NHz; (SEQ ID No:193)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(Doc)2-(Arg)5-GIn-(Arg)4-NH2; (SEO ID No:194)
ACIDIChgýc(AspýHisýDýpheýArgýTrpýGabaýLySHIIA]aýTyFGIy*(Arg)sýG]ný(Arg)rr
NHz; (SEQ ID No:195)
Ac-D-Chg-C(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-ß-Ala-(Arg)5-Gln-(Arg)3-NHz; (SEQ ID No:196)
Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-ß-Ala-Tyr-GIy-(Arg)5-GIn-(Arg)3-NH2; (SEQ ID NO:19?)
AC-hPhe-C(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-ß-Ala-(Arg)5-GIn-(Arg)3-NHz; (SEQ ID No:198)
AC-Nle-C(Cys-His-D-Phe-Arg-D-Tr'p-Apn-Cys)-j3-A1a-Tyr-Gly-(Arg)s-Gln-(Arg)3-
NHi; (SEQ JD No:199)
AC-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Apn-Cys)-ß-Ala-(Arg)5-GIn-(Arg)3-NHZ; (SEQ ID No:200)
AC-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-ß-AIa-Tyr-GIy-(Arg)5-GIn-(Arg)3-NH2; (SEQ ID No:199)
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-ß-AIa-(Arg)5-GIn-(Arg)3-NH2; (SEQ ID No:200)
AC-Nle-C(Cys-His-D-Phe-Arg-D-Trp-ß-Ala-Cys)-js`-Ala-Tyr-Gly-(Arg)s-GIn-(Arg)3-
NHz; (SEQ ID No:201)
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-ß-AIa-Cys)-ß-Ala-(Arg)5-GIn-(Arg)3-NHz; (SEQ ID No:202)
Ac-Nle-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Pen)-,ß-AIa-Tyr-GIy-(Arg)5-Gln-(Arg)3-NH2; (SEQ ID No:203)
Ac-Nle-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Pen)-ß-AIa-GIy-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:203)
AC-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-ß-Ala-(Arg)5-Gln-(Arg)3-NH2; (SEQ lD No:205)
AC-Nle-c(Cys-D-Ala-His-D-Phe-Ai'g-Trp-Pen)-(ß-Ala)2-Tyr-Gly-(Arg)s-Gln-(Arg)s-
NHz; (SEQ ID No:204)
Ac-Nle-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Pen)-(ß-Ala)2-Gly-(Arg)5-GIn-(Arg)3-NHz; (SEQ ID No:204)
AC-Nle-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Pen)-(ß-Ala)2-(Arg)5-GIn-(Arg)3-NH2; (SEQ lD No:205)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-Doc-Tyr-GIy-(Arg)5-Gln-(Arg)3-NH2; (SEQ lD No:207)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-Doc-Gly-(Arg)5-Gln-(Arg)3-NH2; (SEQ ID No:206)
Ac-Nle-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Pen)-Doc-(Arg)5-GIn-(Arg)3-NHz; (SEQ ID No:206)
Ac-Nle-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Pen)-(Doc)2-Tyr-GIy-(Arg)5-GIn-(Arg)3-NH2; (SEQ ID NO:20?)
Ac-Nle-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Pen)-(Doc)2-Gly-(Arg)5-Gln-(Arg)3-NH2; (SEQ ID No:208)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(D0c)2-(Arg)5-GIn-(Arg)3-NHz; (SEO ID No:208)
D-Phe-C(Cys-His-D-(Et)Tyr-Arg-Trp-_/3-Ala-D-Cys)-ß-A1a-Tyr-Gly-(Arg)s-Gln-(Arg)s-
NHz; (SEQ ID No:209)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-ß-Ala-D-Cys)-ß-AIa-(Arg)5-GIn-(Arg)3-NHz; (SEQ ID No:210)
D-Phe-C(Cys-His-D-(Et)Tyr-Arg-Trp-ß-Ala-D-Cys)-ß-AIa-GIy-(Arg)5-GIn-(Arg)3-NHz; (SEQ ID No:209)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-ß-Ala-D-Cys)-ß-AIa-(Arg)5-GIn-(Arg)4-NHZ; (SEQ ID No:211)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-ß-Ala-D-Cys)-(ß-Ala)2-Tyr-Gly-(Arg).=-Gln-
(Arg)3-Nl-lz; (SEQ 1D No:212)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-,B-Ala-D-Cys)-(ß-Ala)2-(Arg)5-GIn-(Arg)3-NHZ; (SEO ID No:213)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-j3-Ala-D-Cys)-(ß-Ala)i-Gly-(Arg)s-Glri-(Arg)s-
NI-h; (SEQ ID No:213)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-ß-Ala-D-Cys)-(ß-Ala)2-(Arg)5-GIn-(Arg)4-NH2; (SEQ ID No:267)
D-Phe-C(Cys-His-D-(Et)Tyr-Arg-Trp-ß-AIa-D-Cys)-D0C-Tyr-Gly-(Arg)s-Gl'n-(Arg)3-
NHz; (SEQ ID No:214)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-ß-Ala-D-Cys)-Doc-(Arg)5-GIn-(Arg)3-NH2; (SEQ ID No:216)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-ß-Ala-D-Cys)-Doc-Gly-(Arg)5-Gln-(Arg)3-NH2; (SEQ ID No:214)
D-Phe-C(Cys-His-D-(Et)Tyr-Arg-Trp-ß-Ala-D-Cys)-Doc-(Arg)5-GIn-(Arg)4-NHz; (SEQ ID NO:21?)
D-Phe-C(CyS-His-D-(Et)Tyr-Arg-Trp-ß-AIa-D-CyS)-(D0C)2-Tyr-GIy-(Arg)5-Gln-(Arg)3-
NHz; (SEQ ID No:215)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-ß-Ala-D-Cys)-(DOC)2-(Arg)5-Gln-(Arg)3-NHZ; (SEQ ID No:216)
D-Phe-C(Cys-His-D-(Et)Tyr-Arg-Trp-ß-Ala-D-CyS)-(DOC)2-CIy-(Arg)3-CIn-(Arg)3-
NI-Ii; (SEQ ID No:215)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-ß-Ala-D-Cys)-(DOC)2-(Arg)5-GIn-(Arg)4-NHZ; (SEQ ID NO:21?)
D-Phe-C(Cys-His-D-(Et)Tyr-hArg-Trp-ß-A]a-D-Cys)-Th r-ß-A] a-Tyr-Gîy-(Arg)s-GI n-
(Arg)3-NHz; (SEQ ID No:218)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-ß-Ala-D-Cys)-Thr-j3-Ala-(Arg)s-Cln-(Arg)3-
NHi; (SEQ ID No:219)
D-Phe-C(Cys-His-D-(Et)Tyr-hArg-Trp-ß-Ala-D-Cy5)-Thr-(/3-A]a)2-Tyr-GIy-(Arg)a-Cln-
(Arg)3-NH2; (SEQ TD No:218)
D-Phe-c(Cys-His-D-(Et)TyT-hArg-Trp-ß-Ala-D-Cys)-Thr-(ß-Ala)2-(Arg)s-GIn-(Arg)s-
NHz; (SEQ ID No:219)
D-Phe-C(CyS-His-D-(Et)Tyr-hArg-Trp-ß-A1a-D-Cys)-Thr-DOC-Tyr-GIy-(Arg)s-G1n-
(Arg)3-NH:; (SEQ ID NO:221)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-ß-AIa-D-Cys)-Thr-Doc-(Arg)5-Gln-(Arg)3-NH2; (SEQ ID No:220)
DýPheýc(CysýI-Iis*DI(Et)TyrýhArgýTrpýßýAlaýDýCysyThr*(D0C)2*TyrýGlyý(Arg)5*Glný
(ArgkNI-Ii; (SEQ ID No:221)
D-Phe-C(Cys-His-D-(Et)Tyr-hArg-Trp-ß-Ala-D-Cys)-Thr-ß-A1a-Tyr-C1y-(Arg)5-G1n-
(Arg)4-NH2; (SEQ ID No:222)
D-Ph e-C(Cys- Hi s-D-(Et)Tyr-hArg-Trp-ß-Al a-D-Cys)-Thr-ß-Al a-(Arg)5-Gln-(Arg)4-
NHz; (SEQ ID No:223)
DýPh 8*C(C)TSIHI sýDý(Et)TyrýhArgýT r pýßýA] aýDýCysyTh r* (fîýAl a )2ýTyrýGIyý(A I'g)5*G] n*
(Arg)4-NHz; (SEQ ID NO:222)
D-Phe-C(Cys-His-D-(Et)Tyr-hArg-Trp-ß-A1a-D-Cys)-Thr-(IS-Ala)2-(Arg)s-Gln-(Arg)4-
NHz; (SEQ ID No:223)
D- Ph e-C(Cys-H i s-D-(Et)Ty r-hArg-T r p-jS-Al a-D-CyS)-Th r-DOC-Tyr-C Iy-(A rg)s-Cl n-
(Arg)4-NHz; (SEQ ID No:224)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-ß-AIa-D-Cys)-Thr-Doc-(Arg)5-G|n-(Arg)4-NH2; (SEO ID No:225)
D-Phe-C(Cys-His-D-(Et)Tyr-hArg-Trp-ß-A1a-D-Cys)-Thr-(Doc)2-Tyr-G]y-(Arg)s-G]n-
(Arg)4-NHz; (SEQ ID No:224)
D-Phe-C(Cys-His-D-(Et)Tyr-hArg-Trpjiâ-Ala-D-Cys)-Thr-(Doc)2-(Arg)s-Gln-(Arg)4-
NHz; (SEQ ID No:225)
DýPheýc(CysýHisýDý(Et)TyrýhArgýBipýjIIAlaýDICysyThrýßýAlaýTyrýGlyý(Arg)5ýGlný
(Arg)3-NH2; (SEQ ID No:227)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-_ß-Ala-D-Cys)-Thr-ß-Ala-Tyr-Gly-(Arg)s-Gln-
(Arg)4-NI-Iz; (SEQ ID No:226)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-_ß-Ala-D-Cys)-Thr-jJ-Ala-(Arg)s-Gln-(Arg)3-
NH2; (SEQ [D No:228)
D-Phe-c(Cys-l-lis-D-(Et)Tyr-hArg-Bip-ß-Ala-D-Cys)-Thr-(jî-Ala)2-Tyr-Gly-(Arg)s-Gln-
(Arg)3-NH2; (SEQ ID No:227)
D-Phe-C(Cys-His-D-(Et)Tyr-hArg-Bip-jÄ-Ala-D-Cys)-Thr-(jî-Ala)2-(Arg)5-Gln-(Arg)3-
NHi; (SEQ ID No:228)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-ß-A]a-D-Cys)-Thr-Doc-Tyr-Gly-(Arg)s-Gln-
(Arg)3-NHz; (SEQ 1D No:229)
D-Phe-C(CyS-His-D-(Et)Tyr-hArg-Bip-jî-Ala-D-Cys)-Thr-D0c-Tyr-Gly-(Arg)5-Gln-
(Arg)4-NH2; (SEQ ID No:230)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-ß-AIa-D-Cys)-Thr-Doc-(Arg)5-GIn-(Arg)3-NHz; (SEO ID No:232)
DIPheýc(CysýHîSIDI(Et)TyrýhArgIBipýßýAIa*DECyS)ET'hrý(D0C)2ETyrEGlyý(Arg)5ýG]ný
(Arg)3-NH2; (SEQ ID No:231)
D-Phe-C(Cys-H i s-D-(Et)Tyr-hArg-Bip-ß-AIa-D-CyS)-Th r-(DOC)2-(Arg)s-GIn-(Arg)3-
NHz; (SEQ ID No:232)
AC-N l e-C(Cy s-D-A] a- Hi s-D-Phe-Arg-Trp-C l y-Cys)-j3-A] a-Ty r-G l y-(Arg)s-C ln-(Arg)s-
NHz; (SEQ ID No:233)
Ac-Nle-c(Cys-D-AIa-His-D-Phe-Arg-Trp-GIy-Cys)-ß-Ala-(Arg)5-GIn-(Arg)3-NHz; (SEO ID No:234)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-ß-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NHz; (SEO ID No:235)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-ß-AIa-(Arg)5-GIn-(Arg)3-NHz; (SEO ID No:236)
NIe-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(ß-Ala)2-Tyr-GIy-(Arg)5-GIn-(Arg)3-NHz; (SEO ID No:235)
NIe-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(ß-Ala)2-(Arg)5-GIn-(Arg)3-NHz; (SEO ID No:236)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-ß-AIa-Tyr-Gly-(Arg)5-GIn-(Arg)4-NHz; (SEO lD NO:23?)
NIe-C(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-ß-AIa-(Arg)5-GIn-(Arg)4-NHz; (SEO ID No:238)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(ß-Ala)2-Tyr-GIy-(Arg)5-GIn-(Arg)4-NHZ; (SEO ID NO:23?)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(ß-Ala)2-(Arg)5-GIn-(Arg)4-NHz; (SEO ID No:238)
NIe-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-Doc-Tyr-Gly-(Arg)5-GIn-(Arg)3-NHZ; (SEO ID No:239)
NIe-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-Doc-(Arg)5-Gln-(Arg)3-NH2; (SEO ID No:240)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(Doc)2-Tyr-GIy-(Ar
NIe-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(Doc)2-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:240)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-D0c-Tyr-GIy-(Arg)5-GIn-(Arg)4-NHz; (SEO lD No:241)
NIe-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-Doc-(Arg)5-GIn-(Arg)4-NH2; (SEO ID No:242)
NIe-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(Doc)2-Tyr-GIy-(Arg)5-GIn-(Arg)4-NHz; (SEO ID No:241)
NIe-C(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(D0c)2-(Arg)5-GIn-(Arg)4-NH2; (SEO ID No:242)
AC-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-ß-AIa-Tyr-GIy-(Arg)5-GIn-(Arg)3-NHz; (SEQ ID No:243)
AC-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-ß-Ala-(Arg)5-GIn-(Arg)3-NH2; (SEQ ID No:244)
AC-NIe-C(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(ß-AIa)2-Tyr-Gly-(Arg)s-Cln-(Arg)s-
NI-Iz; (SEQ ID No:243)
AC-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(ß-Ala)2-(Arg)5-GIn-(Arg)3-NH2; (SEQ ID No:244)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-GIy-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:245)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-GIn-(Arg)3-NHz; (SEO ID No:246)
AC-NIe-C(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(D0C)2-Tyr-Gly-(Arg)s-GIn-(Arg)3-
NHi; (SEQ ID No:245)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-GIn-(Arg)3-NH2; (SEQ ID No:246)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-ß-AIa-Tyr-GIy-(Arg)5-Gln-(Arg)4-NHgs (SEQ ID NO:24?)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-ß-Ala-(Arg)5-GIn-(Arg)4-NH2; (SEQ ID No:248)
AcýNleýc(CysýDýLeu*HisýDýPheýArgýTrpýCysyqîýAla)2›TyrýGlyý(Arg)sýGlný(Arg)4ý
NHi; (SEQ ID No:247)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(ß-Ala)2-(Arg)5-GIn-(Arg)4-NHz; (SEQ ID No:248)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-GIy-(Arg)5-Gln-(Arg)4-NH2; (SEQ lD No:249)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-GIn-(Arg)4-NH2; (SEQ ID No:250)
AC-Nle-C(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(D0C)2-Tyr-Gly-(Arg)5-G1n-(Arg)4-
NHi; (SEQ ID No:249)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-Gln-(Arg)4-NHz; (SEQ ID No:250)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-ß-AIa-Tyr-GIy-(Arg)5-GIn-(Arg)3-NH2; (SEQ ID No:251)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-ß-AIa-(Arg)5-GIn-(Arg)3-NH2; (SEQ ID No:252)
Ac-Nie-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-gs-A1a)2-Tyr-Giy-(Arg)s-Gm-(Arg)3-
NH2; (SEQ ID NO:251)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(ß-Ala)2-(Arg)5-GIn-(Arg)3-NHz; (SEQ ID No:252)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-GIy-(Arg)5-GIn-(Arg)3-NH2; (SEQ ID No:253)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-GIn-(Arg)3-NH2; (SEQ ID No:254)
AC-Nle-C(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(DOC)z-Tyr-Cly-(Arg)5-Gln-(Arg)3-
NHz; (SEQ ID No:253)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-GIn-(Arg)3-NHz; (SEQ ID No:254)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-ß-AIa-Tyr-GIy-(Arg)5-Gln-(Arg)4-NHz; (SEQ ID No:255)
AC-Nle-C(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-ß-Ala-(Arg)5-GIn-(Arg)4-NH2; (SEQ ID No:256)
AC-Nle-C(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(ß-Ala)2-Tyr-Cly-(Arg)5-Cln-(Arg)4-
NHz; (SEQ ID No:255)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(ß-Ala)2-(Arg)5-GIn-(Arg)4-NH2; (SEQ ID No:256)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-GIy-(Arg)5-GIn-(Arg)4-NH2; (SEQ ID No:257)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-GIn-(Arg)4-NH2; (SEQ ID No:258)
AC-NIe-C(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(D0c)2-Tyr-Cly-(Arg)s-Gln-(Arg)4-
NI-Ii; (SEQ ID No:257)
AC-N|e-C(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-Gln-(Arg)4-NHz; (SEQ ID No:258)
NIe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-ß-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (SEQ ID No:259)
NIe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-ß-AIa-(Arg)5-GIn-(Arg)3-NHz; (SEO ID No:260)
NIe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(ß-Ala)2-Tyr-GIy-(Arg)5-GIn-(Arg)3NH2; (SEQ ID No:259)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(ß-Ala)2-(Arg)5-Gln-(Arg)3NHZ; (SEQ ID No:260)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-ß-AIa-Tyr-GIy-(Arg)5-Gln-(Arg)4-NHz; (SEQ ID No:261)
NIe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-ß-AIa-(Arg)5-GIn-(Arg)4-NHz; (SEQ ID No:262)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(ß-Ala)2-Tyr-GIy-(Arg)5-GIn-(Arg)4-NHZ; (SEQ ID No:261)
NIe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(ß-Ala)2-(Arg)5-GIn-(Arg)4-NHz; (SEQ ID No:262)
NIe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-Doc-Tyr-Gly-(Arg)5-GIn-(Arg)3-NH2; (SEQ ID No:263)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-D0c-(Arg)5-Gln-(Arg)3-NH2; (SEQ ID No:264)
NIe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (SEQ ID No:263)
Nle-C(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2; (SEQ ID No:264)
NIe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (SEQ ID No:265)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-Doc-(Arg)5-GIn-(Arg)4-NH2; (SEO ID NO:266)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)2-Tyr-Gly-(Arg)5-G|n-(Ar
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2; (SEQ ID NO:266);
veya bunlarin farmasötik olarak kabul edilen tuzlaridir.
Burada ayrica, memeli denekte insülin direncini kilo kaybederek veya kilo kaybetmeden,
terapötik etkili miktarda Formül (IV) 'e uygun melanokortin reseptörü bilesiginin ve bunlarin
farmasötik olarak kabul edilen tuzlarinin, hidratlarinin, solvatlarinin veya ön ilaçlarinin
asagidaki formüllü (formül (IV) bilesik ile verilmesi yolu ile tedavi etme yöntemi tarif
edilmektedir:
Ac-c(Cys-GIu-His-A1-Arg-AZ-As-Cysy(Pr0)2-Lys-Asp-NHz (lV)
A1 , X-Phe veya 2-Nal'in D-izomeridir, burada X halojendir;
A2 , Bal, 1-Nal, 2-Nal, veya Trp “dir; ve
A3 , Aib, Ala, ,ß-Ala veya Gly,
veya bunlarin farmasötik olarak kabul edilen tuzlaridir.
Memeli deneklerde kilo kaybederek veya kilo kaybi olmaksizin insülin direncini tedavi ettigi
tespit edilen hemen yukaridaki formüllü bilesik örnekleri asagidakileri içermektedir:
Ac-c(Cys-GIu-His-D-4-Br-Phe-Arg-Trp-GIy-Cys)-(Pro)2-Lys-Asp-NHz;(SEQ IDNO:268)
Ac-C(Cys-GIu-His-D-2-Nal-Arg-Trp-AIa-Cys)-(Pro)2-Lys-Asp-NHz; (SEO ID No:269)
Ac-c(Cys-GIu-His-D-2-Nal-Arg-2-Nal-AIa-Cys)-(Pro)2-Lys-Asp-NH2; (SEQ ID No:269)
Ac-c(Cys-GIu-His-D-2-NaI-Arg-1-NaI-AIa-Cys)-(Pr
Ac-c(Cys-GIu-His-D-2-NaI-Arg-Bal-AIa-Cys)-(Pro)2-Lys-Asp-NH2; (SEO ID No:2690)
Ac-c(Cys-GIu-His-D-2-NaI-Arg-2-NaI-ß-AIa-Cys)-(Pr
Ac-c(Cys-GIu-His-D-2-NaI-Arg-2-NaI-Aib-Cys)-(Pr
veya farmasötik olarak kabul edilen tuzlari.
Burada ayrica, memeli denekte insülin direncini kilo kaybederek veya kilo kaybetmeden,
hidantoin kismi Formül (IV), (VI) veya (VII) 'ye uygun olarak modifiye edilmis terapötik etkili
miktarda melanokortin reseptörü bilesiginin ve bunlarin farmasötik olarak kabul edilen
tuzlarinin, hidratlarinin, solvatlarinin veya ön ilaçlarinin verilmesi yolu ile tedavi etme yöntemi
tarif edilmektedir.
Burada ayrica, memeli denekte insülin direncini kilo kaybederek veya kilo kaybetmeden,
terapötik etkili miktarda asagidaki formüle (Formül (V)) uygun melanokortin reseptörü
veya ön ilaçlarinin verilmesi yolu ile tedavi etme yöntemi tarif edilmektedir (bkz. Uluslararasi
(CH2)2-S-S-C(CH3)2-, -(CH2)t-C(O)-NR8-(CH2)r- ve -(CH2),- NRa-C(O)-(CH2)t- ihtiva
eden gruptan seçilmistir;
R1 ve R2 'nin her birisi bagimsiz olarak, H, (C1-C10)alkil veya ikameli (C1-C10)alkildir;
R3 , -OH veya -N H2 'dir;
R4 ve R5 ”nin her birisi bagimsiz olarak, H, (Ci-Cm)alkil veya ikameli (C1-C10)alkildir;
A2 , D-Bal, D-1-Nal, D-2-Nal, D-Phe veya D-(X1,X2,X3,X4,X5)Phe 'dir;
A3 , Arg, hArg, Dab, Dap, Lys veya Orn 'dir;
A4 , Bal, 1-Nal, 2-Nal, (X1,X2,X3,X4,X5)Phe veya Trp 'dir;
R6 ve R7 'nin her birisi, her vakasi için bagimsiz olarak, R6 ve R7 'nin halka olusturmak
üzere bir, birilerine baglanabilmesi kosulu ile H, (C1-C10)alkil, (Ci-C1o)heteroalkil,
ariI(C1-C5)alkil, ikameli (C1-C1Ü)alkil, ikameli (C1-Cio)heteroalkil veya ikameli ariI(C1-
Cs)alkildir;
R8 , H, (C1-C1o)alkil veya ikameli (C1-C1o)alkildir;
r, her vakasi için bagimsiz olarak, 1, 2, 3, 4 veya 5 'dir; ve
t, her vakasi için bagimsiz olarak, 1 veya 2 'dir.
Bir uygulamada, X1 ,in asagidakileri ihtiva eden gruptan seçildigi bilesikler de dahil olmak
üzere yukaridaki formüle uygun bilesigin memeli denekte kilo kaybederek veya kilo
kaybetmeden insülin direncinin tedavisinde yararli oldugu görülmüstür:
Memeli denekte kilo kaybederek veya kilo kaybetmeden insülin direncinin tedavisinde yararli
olan yukaridaki bilesik sinifini temsil eden örnekler asagida belirtilmistir:
c[Hydantoin(C(O)-(Cys-D-Ala))-His-D-Phe-Arg-Trp-Cysl-NHz; (SEO ID NO: 271)
c[Hydantoin(C(O)-(hCys-D-Ala))-His-D-Phe-Arg-Trp-Cys]-NHz; (SEO ID No:271)
c[Hydantoin(C(O)-(Cys-D-AIa))-His-D-2-NaI-Arg-Trp-Cys]-NHz; (SEO ID No:272)
c[Hydantoin(C(O hCys-D-Ala))-His-D-2-NaI-Arg-Trp-Cys]-NHz; (SEO ID No:272)
Asp-D-Ala))-His-D-Phe-Arg-Trp-Lys]-NHz; (SEO ID No:273)
c[Hydantoin(C (O (
(Asp-D-Ala))-His-D-Phe-Arg-Trp-Orn1-NHz; (SEO ID No:273)
c[Hydantoin(C (O
c[Hydantoin(C(O
c[Hydantoin(C(O
c[Hydantoin(C(O (Asp-His))-D-2-NaI-Arg-Trp-Lys]-NHz; (SEO ID No:275)
c[Hydantoin(C(O (Asp-His))-D-Phe-Arg-Trp-Lys]-NH2 (SEO lD NO: 274)
)- Asp-D-AIa))-His-D-Phe-Arg-Trp-Dab]-NHz; (SEO ID No:273
c[Hydantoin(C(O)- (Asp-A30))-D-Phe-Arg-Trp-Lys]-NHz; (SEO ID No:274)
Asp-D-AIa))-His-D-Phe-Arg-Trp-Dap1-NHz; (SEO ID No:273)
c[Hydantoin(C(O (Asp-A50))-D-Phe-Arg-Trp-Lys]-NH2; (SEO ID No:274)
c[Hydantoin(C(O (Asp-A60))-D-Phe-Arg-Trp-Lys]-NHz; (SEO ID No:274)
c[Hydantoin(C(O (Asp-A3c))-D-2-NaI-Arg-Trp-Lys]-NHz; (SEO ID No:275)
c[Hydantoin(C(O (Asp-A50))-D-2-Nal-Arg-Trp-Lys]-NHz; (SEO ID No:275)
c[Hydantoin(C(O (Asp-A60))-D-2-NaI-Arg-Trp-Lys]-NHz; (SEO ID No:275)
c[Hydantoin(C (O (Asp-Aic))-D-Phe-Arg-Trp-Ly51-NHz; (SEO ID No:274)
c[Hydantoin(C(O (Asp-Apc))-D-Phe-Arg-Trp-Lys]-NHz: (SEO ID No:274)
C[Hydantoin(C(O)-(Asp-Aic))-D-2-NaI-Arg-Trp-Lys]-NHz; (SEO ID No:275)
c[Hydantoin(C(O)-(Asp-Apc))-D-2-NaI-Arg-Trp-Lys]-NHz; (SEO ID No:275)
c[Hydantoin-(C(O)-(Asp-Aic))-D-2-NaI-Arg-Trp-Lys]-NH2(SEQ lD No:275)
c[Hydantoin-(C(O)-(Asp-Apc))-D-2-NaI-Arg-Trp-Lys]-NHz (SEO ID No:275)
c[Hydantoin(C(O)-(GIu-D-Ala))-His-D-Phe-Arg-Trp-Orn]-NHz; (SEQ ID No:276)
c[Hydant0in(C(O)-(GIu-D-Ala))-His-D-Phe-Arg-Trp-Dab]-NHz; (SEQ ID No:276) veya
c[Hydant0in(C(O)-(GIu-D-AIa))-His-D-Phe-Arg-Trp-Dap]-NH2, (SEO ID No:276)
c[Hydant0in(C(O)-(GIu-His))-D-Phe-Arg-Trp-Dap1-NHz (SEQ ID NO:27?)
Burada ayrica, memeli denekte insülin direncini kilo kaybederek veya kilo kaybetmeden,
terapötik etkili miktarda Formül (VI) ”ya uygun melanokortin reseptörü bilesiginin ve bunlarin
farmasötik olarak kabul edilen tuzlarinin, hidratlarinin, solvatlarinin veya ön ilaçlarinin
verilmesi yolu ile tedavi etme yöntemi tarif edilmektedir (bkz. bu dokümana referans
gösterilerek bütünü ile dahil edilmis olan Uluslararasi Patent Basvurusu Yayin No.
PCT/USO8/06675):
R1 /Ný
A1 , Asp, Cys, D-Cys, Dab, Dap, Glu, Lys, Orn, Pen veya D-Pen 'dir;
A2 , L- veya D-amino asittir;
A4 , D-Bal, D-1-Nal, D-2-Nal, D-Phe veya D-(X1,X2,X3,X4,X5)Phe 'dir;
A5 , Arg, hArg, Dab, Dap, Lys veya Orn 'dir;
A6 , Bal, 1-Nal, 2-Nal, (X1,X2,X3,X4,X5)Phe veya Trp ,dir;
A7 , Asp, Cys, D-Cys, Dab, Dap, Glu, Lys, Orn, Pen veya D-Pen 'dir;
R1 , H, (Ci-C1o)alkil veya ikameli (C1-C1o)alkildir;
R2 ve R3°ün her birisi, bagimsiz olarak, H, (C1-C10)alkil, (C1-C1o)heteroalkil, ariI(C1-
veya R2 ve R3 siklik kismi olusturmak üzere biri biri ile kaynastirilabilir;
R4 , COZH veya C(O)NH2 'dir;
R5 ve R6 'nin her birisi, bagimsiz olarak, H, (C1-C1o)alkil, (C1-Cio)heter0alkil, ariI(Ci-
C5)alkil, ikameli (C1-C10)alkil, ikameli (C1-C10)heteroalkil veya ikameli ariI(C1-C5)alkildir
veya R5 ve R6 siklik kismi olusturmak üzere biri biri ile kaynastirilabilir;
R7 ve R8 'nin her birisi, bagimsiz olarak, H, (Ci-C10)alkil, (C1-C1o)heteroalkil, ariI(C1-
Cs)alkil, ikameli (Ci-C1o)alkil, ikameli (C1-C10)heteroalkil veya ikameli ariI(C1-
C5)alkildir; veya R7 ve R8 siklik kismi olusturmak üzere biri biri ile kaynastirilabilir;
R9 , H, (C1-Cm)alkil veya ikameli (C1-C10)alkildir; ve
n, her vaka için bagimsiz olarak, 1, 2. 3, 4, 5. 6 veya 7 “dir;
veya bunlarin farmasötik olarak kabul edilen tuzlaridir.
Memeli denekte kilo kaybederek veya kilo kaybetmeden insülin direncinin tedavisinde yararli
olan Formül (VI) 'ya uygun bilesik sinifini örnegi asagidaki sekildeki bilesiklerdir, bu
bilesiklerde:
A1 , Cys 'dir;
A2 , D-Ala, Asn, Asp, Gln, Glu veya D-Phe 'dir;
A3 , His 'dir;
A4 , D-2-Nal veya D-Phe 'dir;
A5 , Arg `dir;
A6 , Trp 'dir; ve
A7 , Cys veya Pen 'dir;
R1, R2, R3, ve R9 'nin her birisi, bagimsiz olarak, H 'dir;
R4 , C(O)NH2'dir;
R5 ve R6 'nin her birisi, bagimsiz olarak, H, (C1-C10)alkil. (C1-C10)heter0alkil, ikameli
(C1-C10)alkil veya ikameli (C1-C10)heteroalkildir veya R5 ve R6 siklik kismi olusturmak
üzere biri biri ile kaynastirilabilir; ve
R7 ve R8 'nin her birisi, bagimsiz olarak, H, (C1-Cio)alkil, (C1-C10)heteroalkil, ikameli
(C1-C10)alkil veya ikameli (C1-C10)heteroalkil `dir;
veya bunlarin farmasötik olarak kabul edilen tuzlaridir.
Memeli deneklerde kilo kaybederek veya kilo kaybi olmaksizin insülin direncini tedavi ettigi
tespit edilen hemen yukaridaki formüllü (Formül (Vl)) bilesik örnekleri asagidakileri
içermektedir:
Hydantoin(C(O)-(Arg-Gly))-c(Cys-GIu-His-D-Phe-Arg-Trp-Cys)-NHz; (SEO ID No:278)
Hydantoin(C(O)-(Nle-GIy))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NHz; (SEO ID No:278)
Hydantoin(C(O )-(GIy-GIy))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (SEO ID No:278)
Hydantoin(C(O)- (Nle- Gly))- c(Cys- -D-Ala- His- D- -Phe-Arg- Trp- Cys)- -NH2; (SEO ID NO: 279)
Hydantoin(C(O)-(Gly-GIy))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NHz; (SEO ID No:279)
Hydantoin(C(O)- (Nle- Gly))- c(Cys- -D- Ala- His- D- Phe- A-r-g Trp- Pen)- NH2; (SEO ID NO: 280)
Hydantoin(C(O)-(Gly-GIy))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2; (SEO ID No:280)
Hydantoin(C(O)- (Ala- Gly))- c(Cys- D-Ala- His- D- Phe- -A-rg-Trp --Cys) NH2; (SEO ID NO: 279)
Hydantoin(C(O)-(D -Ala-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEO ID No:279)
Hydantoin(C(O)- (Aib- Gly))- c(Cys- -D-Ala- His- D- Phe- -A-rg-Trp Cys)- -NH2; (SEO ID NO: 279)
Hydantoin(C(O)-(Val-GIy))-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-NH2; (SEO ID No:279)
Hydantoin(C(O)- (Ile-Gly))- c(Cys- D- Ala- His- D- P-he-Arg- Trp- Cys)- NH2; (SEO ID NO: 279)
Hydantoin(C(O)-(Leu-GIy))-C(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NHz; (SEO lD No:279)
Hydantoin(C(O)- (GIy-Gly))- c(Cys- G-l-u His- D- 2- Nal- -Ar-g Trp- Cys)- NH2; (SEO ID NO: 281)
Hydantoin(C(O )-(Nle-GIy))-c(Cys-Glu-His-D-2-NaI-Arg-Trp-Cys)-NH2; (SEO ID No:281)
Hydantoin(C(O)-(D-Arg-Gly))-c(Cys-GIu-His-D-Phe-Arg-Trp-Cys)-NH2; (SEO ID No:278)
Hydantoin(C(O)-(Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (SEO ID No:278)
Hydantoin(C(O)- (D -Arg-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NHz; (SEO ID No:279)
Hydantoin(C(O)-(Arg-GIy))-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-NH2; (SEO ID No:279)
(C (O)-(D-Arg-Gly))-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NHz; (SEO ID No:282)
Hydantoin(C(O)-(Arg-Gly))-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NHz; (SEO ID No:282)
Hydantoin(C(O)- (Nle- Gly))- c(Cys-Glu- -His- D- Phe- -Arg-Trp- Cys)- N-H2; (SEO ID NO: 278)
Hydantoin(C(O)- (GIy-Gly))- c(Cys- G-l-u His- D- Phe- -A-rg Trp- Cys)- -NH2; (SEO ID NO: 278)
Hydantoin(C (O)-(Nle-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NHz; (SEO ID No:279)
Hydantoin(C(O)-(Gly-GIy))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NHz; (SEO lD No:279)
Hydantoin(C(O)- (Nle- Gly))- c(Cys- D- Ala- His- D- Phe- -A-rg Trp- Pen)- NH2; (SEO ID NO: 280)
Hydantoin(C(O )-(GIy-GIy))-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Pen)-NH2; (SEO ID No:280)
Hydantoin(C(O)-(AIa-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEO ID No:279)
Hydantoin(C(O)-(D-Ala-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEO ID No:279)
Hydantoin(C(O)- (Aib- Gly))- c(Cys- -D-Ala- His- D- Phe- -A-rg-Trp Cys)- -NH2; (SEO ID NO: 279)
Hydantoin(C(O)-(Val-Gly))-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-NH2; (SEO ID No:279)
Hydantoin(C(O)-(lle-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NHz; (SEO ID No:279)
Hydantoin(C(O)-(Leu-GIy))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NHz; (SEO ID No:279)
Hydantoin
Hydantoin C(O -Arg-Gly))-c(Cys-GIu-His-D-Phe-Arg-Trp-Cys)-NH2; (SEO ID No:278)
Arg- GIy))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (SEO ID No:278)
Arg- Gly))-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-NH2; (SEO ID No:279) veya
-Arg-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NHz; (SEO ID No:279)
Ala- -NIe))-c(Cys-GIu-His-D-Phe-Arg-Trp-Cys)-NH2; (SEO ID No:283)
Val- -NIe))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (SEO ID No:283)
Gly-Nle))- c(Cys-Glu-His-D-Phe-Arg-Trp-CyS)-NHz; (SEO lD No:283)
A6c-NIe))-C(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-NH2; (SEO ID No:284)
GIy-Nle))- C(Cys- D- Ala- His- D- Phe- -Arg- Trp- Cys)- NH2;( (SEO ID NO: 284)
Hydantoin C )- (
)- (Ala- Nle))-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-NHz; (SEO ID No:284)
Hydantoin C
Hydantoin C(O
Hydantoin C(O
Hydantoin C(O
Hydantoin C(O
Hydantoin C(O
Hydantoin C(O
Hydantoin C 0
Hydantoin C 0
Hydantoin C(O
Hydantoin C 0
Cha-Nle))-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-NHz; (SEO ID No:284) veya
Aib- Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NHz; (SEO ID No:284)
Gly-Arg))- c(Cys-GIu-His-D-Phe-Arg-Trp-Cys)-NHz; (SEO ID No:285)
( Gly-Arg))- c(Cys-Glu-His-D-2-NaI-Arg-Trp-Cys)-NHz; (SEO ID No:285)
Hydantoin C(O Gly- Arg))-C(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEO ID No:286)
Hydantoin C(O Gly-Arg)) -c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NHz; (SEO ID No:286)
Hydantoin C(O)- (Gly-D -Arg))- c(Cys-GIu-His-D-Phe-Arg-Trp-Cys)-NH2; (SEO ID No:287)
Hydantoin C(O)-(GIy-D -Arg))-c(Cys-GIu-His-D-Phe-Arg-Trp-Cys)-NH2; (SEO ID No:287)
(0)-(Gly-D-Arg))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NHz; (SEO ID No:288)
Hydantoin C(O
( -AIa-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEO ID No:284)
Hydantoin C(O Val- -NIe))-c( Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-NHz; (SEO ID No:284)
Hydantoin C(O Leu- -N-Ie)) C(Cys-D- A-Ia- His-D- Phe- -A-rg-Trp Cys)- -NH2; (SEO ID NO: 284)
Hydantoin(C O
Hydantoin
Hydantoin(C(O)-(Gly-D-Arg))-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NHz; (SEO ID No:288)
Hydantoin(C(O)-(Nle-AIa))-c(Cys-GIu-His-D-Phe-Arg-Trp-Cys)-NHZ (SEO ID NO:289);
veya farmasötik olarak kabul edilen tuzlari.
Burada ayrica, memeli denekte insülin direncini kilo kaybederek veya kilo kaybetmeden,
asagida gösterilen Formül (VII) 'ye uygun yapidaki melanokortin reseptörlerinin ligandlari
olan siklik peptid analoglari sinifina ait olan melanokortin reseptörü Iigandinin terapötik
olarak etkili miktarda verilmesi yolu ile tedavi etme yöntemi tarif edilmektedir (bkz. bu
dokümana referans gösterilerek bütünüyle dahil edilmis olan Uluslararasi Patent Basvurusu
Yayin No. PCT/USO8/06675):
RîXkNOO A1 _A2 A3- A4-A5-
-(CHI- ihtiva
eden gruptan seçilmistir;
R1 ve R5 'nin her birisi bagimsiz olarak, H, (C1-C10)alkil veya ikamelid (C1-C1o)alkildir;
R2 ve R3 'nin her birisi, bagimsiz olarak, H, (C1-C10)alkil, (C1-C10)heteroalkil, ariI(C1-
Cs)alkil, ikameli (C1-C10)alkil, ikameli (C1-C1o)heteroalkil veya ikameli ariI(C1-Cs)alkildir
veya R2 ve R3 halka olusturmak üzere biri biri ile kaynastirilabilir;
R4 , OH veya NH2 'dir;
R6 ve R7 ”nin her birisi, bagimsiz olarak, H, (Ci-C10)alkil veya ikameli (C1-C1o)alkildir;
A1 , L- veya D-amino asittir veya çikarilmistir;
A3 , D-Bal, D-1-Nal, D-2-Nal, D-Phe veya D-(X1,X2,X3,X4,X5)Phe 'dir;
A4 , Arg, hArg, Dab, Dap, Lys veya Om 'dir;
A5 , Bal, 1-Nal, 2-Nal, (X1,X2,X3,X4,X5)Phe veya Trp 'dir;
r, her vaka için bagimsiz olarak 1, 2, 3, 4 veya 5 'dir; ve
t, her vaka için bagimsiz olarak 1 veya 2;
veya bunlarin farmasötik olarak kabul edilen tuzlaridir.
Memeli denekte, kilo kaybederek veya kilo kaybi olmaksizin insülin direncinin tedavisinde
yararli olan Formül (VII) 'ye uygun bilesiklerin bir uygulamasi,
A1 , Ala, D-Ala, Asn, Asp, Gln, Glu veya Gly;
veya farmasötik olarak kabul edilen tuzlaridir.
Memeli denegin, kilo kaybederek veya kilo kaybi olmadan insülin direncinin tedavisinde
yararli olan Formül (VII) 'ye uygun bilesiklerin örnekleri asagidaki bilesikleri içermektedir:
C[Hydantoin(C(O)-(Nle-Cys))-D-AIa-His-D-Phe-Arg-Trp-Cys]-NHz; (SEQ ID No:290)
C[Hydantoin(C(O)-(Ala-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (SEQ ID No:290)
c[Hydantoin(C(O)-(D-AIa-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NHZ; (SEQ ID No:290)
c[Hydant0in(C(O)-(Aib-Cys))-D-AIa-His-D-Phe-Arg-Trp-Cys]-NH2; (SEQ ID No:290)
c[Hydantoin(C(0)-(VaI-Cys))-D-AIa-His-D-Phe-Arg-Trp-Cys]-NH2; (SEQ ID No:290)
C[Hydantoin(C(O)-(Abu-Cys))-D-AIa-His-D-Phe-Arg-Trp-Cys]-NHz; (SEQ ID No:290)
c[Hydant0in(C(O)-(Leu-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NHz; (SEQ ID No:290)
c[Hydant0in(C(O)- (Ile-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (SEO ID No:290)
c[Hydant0in(C(O)- (Cha- Cys))- -D Ala- His- D- Phe- -Arg- Trp- Cys]- -;NH2 (SEO ID NO: 290)
c[Hydant0in(C(O) -(AGC-Cys))-D-AIa-His-D-Phe-Arg-Trp-Cys]-NH2; (SEQ ID No:290)
c[Hydant0in(C(O)- (Phe- Cys))-D-AIa-His-D-Phe-Arg-Trp-Cy51-NHz; (SEQ ID No:290)
c[Hydant0in(C(O) -(GIy-Cys))-D-AIa-His-D-Phe-Arg-Trp-Cys]-NH2; (SEQ ID No:290) veya
c[Hydant0in(C (O)- (Gly- Cys))- Glu- His- D- Phe- -A-rg Trp- Cys]- NHZ; (SEO ID NO: 291) veya
c[Hydant0in(C (O )-(GIy-Cys))-Glu-His-D-Phe-Arg-Trp-Cys]-NH2(SEQ ID NO:291);
veya bunlarin farmasötik olarak kabul edilen tuzlari.
Burada ayrica, memeli denekte insülin direncini kilo kaybederek veya kilo kaybetmeden,
terapötik etkili miktarda Formül (VIII) 'e uygun melanokortin reseptörü Iigandinin verilmesi
yolu ile tedavi etme yöntemi tarif edilmektedir (bkz. Uluslararasi Patent Basvurusu Yayin No.
A0, aromatik amino asittir; A1 , Acc, HN-(CH2)m-C(O), L- veya D-amino asittir; A2,
Asp, Cys, D-Cys, hCys, D-hCys, Glu, Pen, veya D-Pen 'dir; A3 , Aib, Ala, ß-Ala, Gaba,
Thi, veya 3-Thi 'dir; A5, D-Bal, D-1-Nal, D-2-Nal, D-Phe, L-Phe, D-
(X1,X2,X3,X4,X5)Phe, L-Phe, D-Trp veya D-(Et)Tyr 'dir; A6 , Arg, hArg, Dab, Dap, Lys,
Orn, veya HN-CH((CH2)n-N(R4R5))-C(O) `dur; A7, Bal, D-Bal, Bip, D-Bip, 1-Nal, D-1-
Nal, 2-Nal, D-2-Nal, veya D-Trp 'dir; A8 , Acc, Aha, Ahx, Ala, D-Ala, ß-Ala, Apn, Gaba,
Gly, HN-(CH2)S-C(O) 'dur veya çikarilmistir; A9, Cys, D-Cys, hCys, D-hCys, Dab,
Dap, Lys, Orn, Pen, veya D-Pen 'dir; Am, Acc, HN-(CH2)t-C(O), L- veya D-amino
asittir veya çikarilmistir; R1 , OH, veya NH2 'dir; R2 ve R3 'nin her birisi, her vaka için
Cso)heter0alkil, ikameli (C1-C30)asil, ikameli (Cz-C30)alkenil, ikameli (Cz-C30)alkinil,
ikameli ariI(C1-Cao)a|kil, ve ikameli ariI(C1-C30)asil ihtiva eden gruptan seçilmistir;
R4 ve R5 'nin her birisi, her vaka için bagimsiz olarak, H, (C1-C40)alkil, (C1-
C4o)asil, ikameli (C1-C40)alkil, ikameli (C1-C40)heteroalkil, ikameli (C1-C4o)asil, ikameli
(C1-C40)alkilsulf0nil, veya -C(NH)-NH2*dir;
m, her vaka için bagimsiz olarak, 1, 2, 3, 4, 5,6 veya 7 7dir;
n, her vaka için bagimsiz olarak, 1, 2, 3, 4 veya 5 'dir;
8, her vaka için bagimsiz olarak, 1, 2, 3, 4, 5, 6, veya 7 'dir;
t, her vaka için bagimsiz olarak, 1, 2, 3, 4, 5, 6, veya 7 dir;
X1, X2, X3, X4, ve X5'in her birisi, her vaka için bagimsiz olarak, H, F, CI, Br, I, (C1-
1o)alkinil, aril, ikameli aril, OH, NH2, N02, veya CN 'dir; su kosulla ki,
(I). R4, (C1-C4o)asil, aril(C1-C40)asil, ikameli (C1-C4O)asil, ikameli aril(C1-
C40)asil, (C1-C4o)alkilsulfonil, veya -C(NH)-NH2 ise, bu durumda R5, H veya
(C1-C4g)alkil, (Ci-C40)heteroalkil, (Cz-C4o)alkenil, (Cz-C40)alkinil, ariI(C1-C4o)alkil,
ikameli (C1-C40)alkil, ikameli (C1-C4o)heteroalkil, ikameli (Cz-C40)alkenil, ikameli
(Cz-C40)alkinil, veya ikameli aril(Ci-C4o)alkildir;
Cso)asil ise, bu durumda R3, H, (C1-C30)alkil, (Ci-C30)heter0alkil, (Cz-
C30)alkenil, (C2'C30)alkInII, aril(C1-Cso)alkil, ikameli (Ci-Cso)alkil, ikameli (C1-
Cgo)heteroalkil, ikameli (Cz-C30)alkenil, ikameli (Cz-Cgo)alkinil, veya ikameli
aril(C1-C30)alkildir;
(III). A2, Cys, D-Cys, hCys, D-hCys, Pen, veya D-Pen ise, bu durumda A9,
Cys, D-Cys, hCys, D-hCys, Pen, veya D-Pen 'dirs
(IV). A2 , Asp veya Glu ise, bu durumda A9, Dab, Dap, Orn, veya Lys “dir;
(V). A8 , Ala veya Gly ise, bu durumda A1 , Nle degildir; veya
bunlarin farmasötik olarak kabul edilen tuzlaridir.
Memeli denegin, kilo kaybederek veya kilo kaybi olmadan insülin direncinin tedavisinde
yararli olan hemen yukaridaki formüle uygun bilesik grubu örnegi asagida verilmistir, burada,
A0 , 1-Nal, 2-Nal, His, Pff, Phe, Trp, veya Tyr 'dir;
A1 ,Arg `dir;
A2 , Cys 'dir;
A3 , D-Ala 'dir;
A4 , His 'dir;
A5 , D-Phe 'dil'
A6 , Arg 'dir;
A7 , Trp 'dir
A8 çikarilmis;
A9 , Cys 'dir; ve
A10 çikarilmis;
veya bunlarin farmasötik olarak kabul edilen tuzlaridir.
Memeli denegin, kilo kaybederek veya kilo kaybi olmadan insülin direncinin tedavisinde
yararli olan hemen yukaridaki bilesik grubu örnekleri asagidaki formülün bilesikleri:
Ac-Tyr-Arg-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-NHz; (SEQ lD No:292)
Ac-2-Nal-Arg-C(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-NHz; (SEQ ID No:292)
Ac-1-Nal-Arg-c(Cys-D-AIa-His-DPhe-Arg-Trp-Cys)-NH2; (SEQ ID No:292)
Ac-Phe-Arg-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-NHz; (SEQ ID No:292)
Ac-Trp-Arg-C(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-NHz; (SEQ ID NO:292)
Ac-Pff-Arg-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-NHz; (SEQ lD No:292)
H-His-Arg-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-NHz; (SEQ ID NO:293) veya
Ac-His-Arg-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-NHz; (SEQ ID No:292)
veya bunlarin farmasötik olarak kabul edilen tuzlaridir.
Bir baska uygulamada, memeli denegin, kilo kaybederek veya kilo kaybi olmadan insülin
direncinin tedavisinde yararli olan yukarida tanimlanan Formül (I), (II), (III), (IV), (V), (VI),
(VII) veya (VIII) bilesigi veya bilesikleri veya bunlarin farmasötik olarak kabul edilen tuzlari
ihtiyaç duyan söz konusu denege farmasötik olarak kabul edilen bir tasiyici veya seyreltici ile
birlikte bir bilesim olarak verilir.
Burada tarif edilen bir uygulama, ihtiyaç duyan bir denegin insülin direncini tedavi etmek için
kullanilan ve etkili miktarda melanokortin reseptörü 4 agonistinin periferik yol ile verilmesini
içeren tedavi yöntemidir.
Bir uygulamada, ihtiyaci olan denegin, beraberinde kilo kaybederek veya kilo kaybi
olmaksizin insülin direncinin tedavisinde yararli olan melanokortin reseptörü 4
asagidakilerden:
Ac-NIe-c(Asp-His-D-Phe-Arg-Trp-ß-AIa-Lys)-NHz; SEQ ID No:1
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-AGc-Lys)-NHZ; SEQ ID No:1
Ac-NIe-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-NHz; SEQ ID No:2
D-Phe-C(Cys-His-D-Phe-Arg-Trp-AIa-D-Cys)-Thr-NHz; SEQ ID NO:3
D-Phe-c(Cys-His-D-Phe-Arg-Trp-ß-Ala-D-Cys)-Thr-NHz; SEQ ID No:3
D-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-D-Cys)-Thr-NHz; SEQ ID No:3
Ac-NIe-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH2; SEQ ID No:2
Ac-NIe-c(Asp-His-D-Phe-Arg-Trp-Apn-Lys)-NHz; SEQ ID NO:4
Ac-Aöc-C(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NHz; SEQ lD NO:5
Ac-D-2-Nal-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NHz; SEQ ID NO:6
Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NHz; SEQ ID No:6
Ac-NIe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NHz; SEQ ID No:6
Ac-NIe-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-NH2; SEQ ID No:7
Ac-NIe-C(Cys-ß-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; SEO ID NO:7
Ac-NIe-c(Cys-Gaba-His-D-Phe-Arg-Trp-Cys)-NH2; SEO ID No:7
Ac-Nle-c(Cys-Aib-His-D-Phe-Arg-Trp-Cys)-NHz; SEO ID No:7
Ac-NIe-c(Cys-Gly-His-D-Phe-Arg-Trp-Cys)-NH2; SEO ID No:7
Ac-NIe-c(D-Cys-AIa-His-D-Phe-Arg-Trp-Cys)-NH2; SEO ID No:8
Ac-NIe-c(D-Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-NH2; SEO ID No:8
Ac-NIe-c(D-Cys-ß-AIa-His-D-Phe-Arg-Trp-Cys)-NHz; SEQ ID No:8
Ac-Nle-c(D-Cys-Gaba-His-D-Phe-Arg-Trp-Cys)-NHz; SEO lD No:8
Ac-NIe-c(D-Cys-Aib-His-D-Phe-Arg-Trp-Cys)-NHz; SEO ID No:8
Ac-NIe-c(D-Cys-GIy-HIs-D-Phe-Arg-Trp-Cys)-NHz; SEO ID No:8
Ac-NIe-c(Cys-D-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; SEO ID No:9
Ac-NIe-C(Cys-ß-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; SEO ID No:9
Ac-NIe-c(Cys-Gaba-His-D-Phe-Arg-Trp-D-Cys)-NH2; SEO ID No:9
Ac-NIe-c(Cys-Aib-His-D-Phe-Arg-Trp-D-Cys)-NHz; SEO ID No:9
AC-Nle-c(Cys-Gly-His-D-Phe-Arg-Trp-D-Cys)-NHz; SEO ID No:9
Ac-NIe-c(D-Cys-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2; SEO ID NO:10
Ac-NIe-c(D-Cys-D-AIa-His-D-Phe-Arg-Trp-D-Cys)-NHz; SEO ID NO:10
Ac-NIe-c(D-Cys-ß-Ala-His-D-Phe-Arg-Trp-D-Cys)-NHz; SEO ID NO:10
Ac-NIe-c(D-Cys-Gaba-His-D-Phe-Arg-Trp-D-Cys)-NH2; SEO ID NO:10
Ac-NIe-c(D-Cys-Aib-His-D-Phe-Arg-Trp-D-Cys)-NH2; SEO ID NO:10
Ac-OiC-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; SEO ID NO:11
Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NHz; SEO ID NO:11
Ac-hCha-C(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; SEO ID NO:11
Ac-D-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-LyS)-NHz; SEO ID NO:11
Ac-Nip-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NHz; SEO ID NO:11
Ac-hPro-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NHZ; SEO ID NO:11
Ac-hLeu-C(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NHz; SEO ID NO:11
AC-Phe-C(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NHz; SEO ID NO:11
Ac-D-Phe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2; SEO ID NO:11
Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NHz; SEQ ID NO:11
n-butanoyI-Cha-C(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NHz; SEO ID NO:12
Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NHz; SEO ID NO:11
Ac-ß-hMet-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NHz; SEO ID NO:11
Ac-Gaba-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NHz; SEO lD NO:11
Ac-Cha-c(Asp-His-D-Phe-Arg-D-Trp-AIa-Lys)-NH2; SEO ID NO:13
Ac-hCha-C(Asp-His-D-Phe-Arg-D-Trp-AIa-Lys)-NHz; SEO ID NO:13
AC-Leu-C(Asp-His-D-Phe-Arg-D-Trp-AIa-Lys)-NHz; SEO ID NO:13
Ac-hLeu-c(Asp-His-D-Phe-Arg-D-Trp-AIa-Lys)-NHz; SEO ID NO:13
Ac-Phe-0(Asp-His-D-Phe-Arg-D-Trp-AIa-Lys)-NHz; SEQ ID NO:13
Ac-NIe-c(Asp-His-D-Phe-Arg-D-Trp-D-Ala-Lys)-NHz; SEQ ID NO:14
Ac- Nle- -c(Asp-His-D-Phe-Arg-D-Trp-ß-AIa-Lys)-NHz; SEQ ID NO:14
Ac- Nle- c-(Asp-His-D-Phe-Arg-D-Trp-Gaba-Lys)-NHz; SEQ ID NO:14
Ac-NIe-c c(Asp-His-D-Phe-Arg-D-Trp-Aha-Lys)-NHz; SEQ ID NO:14
Ac- Nle- c-(Asp-His-D-Phe-Arg-D-Trp-Apn-Lys)-NH2; SEQ ID NO:14
Ac- Nle- c-(Cys-His-D-Phe-Arg-D-Trp-Apn-Cys)-NHz; SEQ ID NO:15
Ac- Nle- -c(Cys-His-D-Phe-Arg-D-Trp-Gaba-Cys)-NHz; SEQ ID NO:15
Ac- Nle- -c(Cys-HIs-D-Phe-Arg-D-Trp-Ahx-Cys)-NHz; SEQ ID NO:15
Ac- Nle- 0-(Cys-HIs-D-Phe-Arg-D-Trp-ß-AIa-Cys)-NHz; SEQ ID NO:15
Ac-NIe-C(Cys-His-D-Phe-Arg-D-Trp-D-Ala-Cys)-NH2; SEQ ID NO:15
Ac-NIe-c(Cys-D-Ala-His-D-2-NaI-Arg-Trp-Cys)-NHz; SEQ ID NO:16
Ac-NIe-c(Cys-D-Ala-His-D-2-NaI-Arg-2-NaI-Cys)-NH2; SEQ ID NO:16
Ac-NIe-c(Cys-D-Ala-His-D-2-NaI-Arg-1-NaI-Cys)-NH2; SEQ ID NO:16
n-butanoyl-NIe-c(Cys-D-AIa-His-D-Phe-Arg-2-NaI-Cys)-NHz; SEQ ID NO:17
n-butanoyI-NIe-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NHz; SEQ ID NO:17
Ac-NIe-c(Cys-D-Ala-His-D-Phe-Arg-2-Nal-Cys)-NHz; SEQ ID NO:18
Ac- Nle- c-(Cys-D-Ala-His-D-Phe-Arg-1-NaI-Cys)-NH2; SEQ ID NO:18
Ac-NIe-c c(Cys-D-AIa-His-D-Phe-Arg-Bal-Cys)-NH2; SEO ID NO:18
Ac- Nle- -c(Cys-D-GIu-His-D-Phe-Arg-Trp-Cys)-NHz; SEQ ID NO:61
Ac- Nle- -c(Asp-HIs-D-Phe-Arg-Trp-D-AIa-LyS)-NHz; SEQ ID NO:19
Ac-NIe-c(Cys-D-Ala-His-D-2-NaI-Arg-Bal-Cys)-NHz; SEQ ID NO:20
Ac-NIe-C(Pen-D-Ala-His-D-Phe-Arg-Trp-Cys)-NHz; SEQ ID NO:21
Ac-NIe-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Pen)-NHz; SEQ ID NO:22
Ac-NIe-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Pen)-NHz; SEQ ID NO:22
D-Phe-c(Cys-His-D-Phe-hArg-Trp-ß-AIa-D-Cys)-Thr-NH2; SEQ ID NO:23
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-,B-AIa-D-Cys)-Thr-NHz; SEQ ID NO:24
D-Phe-c(Cys-His-D-Phe-Arg-Bip-ß-Ala-D-Cys)-Thr-NHz; SEQ ID NO:25
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-ß-Ala-D-Cys)-Thr-NH2; SEQ ID NO:24
D-Phe-c(Cys-His-D-Phe-hArg-Bip-ß-Ala-D-Cys)-Thr-NHz; SEQ ID NO:26
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-ß-AIa-D-Cys)-Thr-NHz; SEQ ID NO:26
NIe-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NHz; SEQ ID NO:27
Ac-NIe-c(Asp-D-Ala-His-D-Phe-Arg-Trp-Lys)-NHz; SEQ ID NO:28
Ac-NIe-c c(Asp-D -Ala- His- D- Phe- -A-rg --Bal -Lys)- -NH2; SEQ ID NO: 28
A0- Nle- -c(-Cys -D-Ala His- D- Phe- -A-rg-Trp-Pen) -;OH SEQ ID NO: 29
A0- Nle- C-(-Cys -D-Abu His- D- --Phe-Arg-Trp Cys)- NH2; SEQ ID NO: 30
Ac-NIe-C(Cys-D-Val-His-D-Phe-Arg-Trp-CyS)-NH2; SEO ID NO:30
Ac-NIe-c(Cys-D-IIe-His-D-Phe-Arg-Trp-Cys)-NH2; SEO ID NO:30
Ac-NIe-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-NHz; SEO lD NO:30
Ac-NIe-c(Cys-D-TIe-His-D-Phe-Arg-Trp-Cys)-NHz; SEO ID NO:30
Ac-NIe-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-NHz; SEO ID NO:30
Ac-NIe-c(Pen-His-D-Phe-Arg-Trp-Gaba-Cys)-NHz; SEO ID NO:31
Ac-NIe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; SEO ID NO:32
Ac-Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; SEO ID NO:32
Ac-Leu-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NHz; SEO ID NO:33
Ac-Cha-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NHz; SEO ID NO:33
Ac-IIe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NHz; SEO ID NO:33
Ac-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NHz; SEO ID NO:33
AC-VaI-C(Cys-His-D-Phe-Arg-Trp-Gaba-CyS)-NH2; SEO ID NO:33
Ac-2-Nal-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NHz; SEO ID NO:33
NIe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NHz; SEO lD NO:34
Phe-C(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2; SEO ID NO:34
AC-NIe-c(Cys-3-Pal-D-Phe-Arg-Trp-Gaba-Cys)-NH2; SEO ID NO:35
Ac-NIe-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-OH; SEO ID NO:36
Ac-Nle-c(Cys-His-Phe-Arg-D-Trp-Gaba-Cys)-NH2; SEO ID NO:37
Ac-NIe-c(Asp-His-D-2-NaI-Arg-Trp-AIa-Lys)-NHz; SEO ID NO:38
Ac-NIe-c(Asp-His-D-2-NaI-Arg-Trp-ß-AIa-Lys)-NHz; SEO ID NO:38
Ac-NIe-c(Cys-His-D-2-Nal-Arg-Trp-Gaba-Cys)-NHz; SEO ID NO:39
Ac-NIe-c(Cys-His-D-2-NaI-Arg-Trp-Ahx-Cys)-NHz; SEO ID NO:39
Ac-hPhe-c(Asp-His-D-2-NaI-Arg-Trp-Gaba-Lys)-NHz; SEO ID NO:40
Ac-Cha-C(Asp-His-D-2-NaI-Arg-Trp-Gaba-Lys)-NHz; SEO ID NO:40
Ac-NIe-c(Asp-HIs-D-Phe-Arg-Trp-ß-AIa-Lys)-OH; SEO ID NO:41
Ac-NIe-C(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-OH; SEO ID NO:42
D-Phe-c(Cys-His-D-Phe-Arg-Trp-AIa-D-Cys)-Thr-OH; SEO ID NO:43
D-Phe-c(Cys-His-D-Phe-Arg-Trp-ß-AIa-D-Cys)-Thr-OH; SEO ID NO:43
D-Phe-C(Cys-His-D-Phe-Arg-Trp-Gaba-D-Cys)-Thr-OH; SEO ID NO:43
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-OH; SEO lD NO:42
Ac-NIe-c(Asp-His-D-Phe-Arg-Trp-Apn-Lys)-OH; SEO ID NO:41
Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; SEO ID NO:44
Ac-NIe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; SEO lD NO:44
Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; SEO ID NO:44
Ac-D-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; SEO ID NO:44
Ac-hCha-C(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; SEO ID NO:44
Ac-D-Chg-C(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; SEO ID NO:44
Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH; SEO ID NO:44
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Gaba-Cys)-OH; SEO lD NO:45
Ac-NIe-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-OH; SEO ID NO:45
Ac-NIe-c(Cys-His-D-Phe-Arg-D-Trp-ß-AIa-Cys)-OH; SEO ID NO:45
Ac-NIe-c(Cys-His-D-Phe-Arg-D-Trp-D-AIa-Cys)-OH; SEO ID NO:45
Ac-NIe-c(Cys-D-AIa-His-D-2-NaI-Arg-Trp-Cys)-OH; SEO ID NO:46
Ac-NIe-c(Cys-D-Ala-His-D-2-NaI-Arg-2-NaI-Cys)-OH; SEO ID NO:46
Ac-NIe-c(Cys-D-Ala-His-D-2-NaI-Arg-1-NaI-Cys)-OH; SEO ID NO:46
Ac-NIe-c(Cys-D-Ala-His-D-2-NaI-Arg-Bal-Cys)-OH; SEO ID NO:46
Ac-NIe-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Cys)-OH; SEO ID NO:47
Ac-NIe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-OH; SEO ID NO:48
AC-Arg-C(Cys-D-Ala-His-D-2-NaI-Arg-Trp-Cys)-NHz; SEO ID NO:49
Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NHz; SEO ID NO:50
AC-D-Arg-C(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NHZ; SEO ID NO:50
Ac-D-Arg-C(Cys-D-AIa-His-D-Phe-Arg-Trp-Pen)-NHz; SEO ID NO:51
AC-D-Arg-C(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2; SEO ID NO:52
Ac-Arg-C(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NHz; SEO ID NO:52
Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NHz; SEO ID NO:51
Ac-D-Arg-c(Asp-His-D-Phe-Arg-Trp-AIa-Lys)-NH2; SEO ID NO:53
Ac-Arg-c(Asp-His-D-Phe-Arg-Trp-AIa-Lys)-NH2; SEO ID NO:53
Ac-NIe-c(Cys-S-PaI-D-Phe-Arg-Trp-Gaba-Cys)-NH2; SEO ID NO:35
Ac-NIe-c(Cys-D-AIa-His-D-Phe-Arg-Trp-GIy-Cys)-NHz; SEO ID NO:54
Ac-NIe-c(Cys-D-Ala-His-D-Phe-Arg-Trp-D-AIa-Cys)-NH2; SEO ID NO:54
Ac-NIe-c(Cys-D-Ala-His-D-Phe-Arg-Trp-ß-AIa-Cys)-NHz; SEO ID NO:54
Ac-NIe-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gaba-Cys)-NHz; SEO ID NO:54
Ac-NIe-C(Cys-D-Ala-His-D-Phe-Arg-Trp-Apn-Cys)-NHz; SEO ID NO:54
AC-C(Cys-GIu-His-D-Phe-Arg-Trp-AIa-Cys)-NH2; SEO ID NO:55
Ac-c(Cys-GIu-His-D-Phe-Arg-2-Nal-AIa-Cys)-NHz; SEO ID NO:55
Ac-c(Cys-D-Ala-His-D-Phe-Arg-Trp-AIa-Cys)-NH2; SEO ID NO:56
Ac-C(Cys-D-Ala-His-D-Phe-Arg-2-Nal-AIa-Cys)-NHz; SEO ID NO:56
Ac-NIe-c(Cys-D-Ala-His-D-Phe-Arg-Trp-AIa-Cys)-NHz; SEO ID NO:57
Ac-NIe-c(Cys-D-Ala-His-D-Phe-Arg-Trp-ß-AIa-Cys)-NHz; SEO ID NO:57
Ac-NIe-c(Asp-D-Ala-His-D-Phe-Arg-BaI-AIa-Lys)-NHz; SEO ID NO:58
Tyr-GIy-Arg-(Lys)2-(Arg)2-GIn-(Arg)3-Nle-C(Asp-His-D-2-Nal-Arg-Trp-Lys)-NH2;(SEQIDN0260)
Tyr-Gly-Arg-(Lys)2-(Arg)2-Cln-(Arg)3-Doc-Nle-C(Asp-His-D-2-Nal-Arg-Trp-Lys)-
NHz; (SEQ ID NO:61)
Nle-C(Asp-His-D-Z-Nal-Arg-Trp-Lys)-j3-A1a-Tyr-Cly-AIö-(Lysk-(Argh-Ch'v(Arg)3-
NHz; (SEQ ID NO:62)
Ac-Nle-c(Asp-His-D-Z-Nal-Arg-Trp-Lys)-_/3-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)z-Gln-
(Arg)3-Nl-lz; (SEQ ID NO:62)
N |e-c(Asp-H1' s-D-2-N a I -Ar g-Trp- Lys)-(D 0C)i-Tyr-GIy-Arg-(Lys)2- (Arg)2-G ln-(Arg)3-
NHz; (SEQ [D NO:63)
AC-N]e-C(Asp-His-D-2-Nal-Arg-Trp-Lys)-(Pro)2-Lys-Asp-Tyr-Gly-Arg-(Lys)2-(Arg)2-
AC-C(Cys-Clu-His-D-2-NaI-Arg-Trp-Cly-Cys)-(Pro)2-Lys-Asp-Ty r-G]y-Arg-(Lys)2-
(Arg)2-G1n-(Arg)3-NH2; (SEQ ID NO:65)
AC-N le-C(Asp-His-D-2-N al-Arg-Trp- Lys)- (fl-Ala)2-Tyr-Cly-Arg-(Lys): (Arg)2-Cln-
(Arg)3-NH2; (SEQ 1D N 066)
Ac-Nle-c(Asp-1-1is-D-2-Nal-Arg-Trp-Lys)-(Pr0)2-Lys-Asp-Doc-T).'r-Gly-Arg-(Lys)2-
(Arg)z-C1n-(Arg)s-NI-Iz; (SEQ ID NO:67)
ACIC(CySIGILiýHisýDIZNa]-ArgýTrpýGIyICys)I(Pr0)2ýLysýAspýDoCýTyrýGlyýArgý
(Lys)2-(Arg)_-GIn-(Arg)3-NH2; (SEQ ID NO:68)
AC-C(Cys-C lu -Hi s-D-2-N a l-Arg-Trp-Al a-Cys)-( Pr0)z- Lys-Asp-ß-Ala-Tyr-G ly-Arg-
(Lys)2-(Arg)2-G1n-(Arg)a-NH2; (SEQ ID NO:69)
AC-C(Cys-Glu-His-D-2-N al-Arg-Trp-Ala-Cys)-(Pr0)_-Lys-Asp-Do C-Tyr-Gly-Arg-
(Lys)2-(Arg)2-Gln-(Arg)3-NHz; (SEQ 1D NO:69)
Ac-Nle-c(Asp-His-D-Z-Nal-Arg-Trp-Lys)-(D0c)z-Tyr-Gly-Arg-(Lys)2-(Arg)2-Clri-
AC-C(Cys-GlLi-HiS-D-2-Nal-Arg-2-Na]-AIa-Cys)-(Pr0)2-Lys-Asp-_ß-Ala-Tyr-Gly-Arg-
(Lys)2-(Arg)2-GIn-(Arg)3-NH2; (SEQ ID NO:71)
AC-C(CyS-Glu-His-D-Z-Nal-Arg-Bal-Ala-Cys)-(Pr0)2-Lys-Aspj13-Ala-(Arg)s-Gln-
(Arg)3-NH2; (SEQ ID NO:72)
AC-C(Cys-GlLI-His-D-Z-NaI-Arg-BaI-A]a-Cys)-(Pr0)2-Lys-Asp-j3-A]a-CIy-(Arg)s-G1n-
(Arg)3-NHi,' (SEQ ID NO:73)
AC-C(CyS-Glu-His-D-2-Nal-Arg-Ba]-Ala-Cys)-(Pr0)2-Lys-Asp-j3-AIa-Tyr-GIy-(Arg)s-
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-AJa-Cys)-(Pr0)2-Lys-Asp-ß-Ala-Tyr-Gly-Arg-
(Lys)2-Arg-Gln-(Arg)4-NI-Iz; (SEQ ID NO:75)
AC-C( CyS-Clu-His-D-Z-N al-Arg-Trp-AJ a-Cys)- (Pro)_-Lys-ASp-ß-Ala-Tyr-Cly-Arg-
(Lys)2-Gln-(Arg)5-NH2; (SEQ ID NO:76)
AC-C(Cys-C] u -Hi s-D-2-Nal -A rg-Trp-A] a-Cys)-(Pr0)_-Lys-Asp-j3-AIa-Ty r-Cly-A rg-
Lys-Gl'n-Lys-(Arg)s-NH2; (SEQ ID NO:77)
AC-C(Cys-G1 Li -Hi s-D-2-Na 1 -A rg-Trp-A] a-Cys)- (P r0)i-Lys-Asp-ß-Ala-Ty r-GIy-A rg-
(Lys)2-(Arg)4-G1n-Arg-NHz; (SEQ ID NO:78)
ACIC(Cys*Gluýl-1ISID*2*NalýArgIBalýAlaýCys)ý(Pro)2*LysýAspßýAlaýTyrýAibýArgý
(Lys)2-(Arg)2-Cln-(Arg)3-NH:; (SEQ ID NO:79)
Ac-C(Cys-Glu-His-D-2-Nal-Arg-l-Nal-Ala-Cys)-(Pro)z-Arg-Asp-_ß-Ala-(Arg)s-Gln-
(Arg)3-NH2; (SEQ ID NO:80)
AC-C(CyS-CI u -H is-D-Z-NaI-Arg-î -Nal-A] a-Cys)-(Pr0)2-Lys-Asp-ß-A] a-(Arg).=-C]'n-
(Arg)3-NH2; (SEQ ID NO:80)
AC-C(Cys-GIu-His-D-2-NaI-Arg-î-Nal-Ala-Cys)-(Pr0)i-Lys-Asp-ß-Ala-(Argy-Gln-
(Arg)3-NH2; (SEQ ID NO:81)
AC-C( Cys-Glu-His-D-Z-N al-AIb-Z-N al-Al a-Cys)-(Pro)_-Arg-Asp-_ß-Ala-(Ar g)5-Gln-
(Arg)3-NHz; (SEQ ID NO:82)
Ac-c(Cys-Glu-His-D-Z-Nal-Arg-Z-Nal-Ala-Cys)-(Pr0)2-Lys-Asp-_/3-Ala-(Arg)s-Gln-
(Arg)3-Nl-]2; (SEQ 1D NO:82)
AC-C(Cys-GIu-His-D-2-NaI-Arg-2-Na]-Ala-Cys)-(Pr0):-Ly5-Asp-j3-A]a-(Argß-Gln-
(Arg)3-NH2; (SEQ ID NO:81)
AC-C(CyS-Clu -Hi s-D-2-Na l-Arg-Ba I-AI a-Cys)-( Pro)2-Arg-Asp-jj-AIa-(Argß-Gln-
(Arg)3-NH2; (SEQ ID NO:83)
AC-C(Cys-G1u-His-D-Z-Nal-Arg-BaI-A]a-Cys)-(Pr0)2-Arg-As p-ß-AIa-(Argß-Gîn-
(Arg)3-NHi; (SEQ ID NO:84)
AC-C(Cys-CIu-His~D-2-Na]-Arg~BaI-A1a-Cys)-(Pr0)2-Lys-Asp713-A1a-(Arg)(,-C;]n-
(Arg)3ýNHz; (SEQ TD NO:83)
Ac-c(Cys-Glu-His-D-2-N al-Arg-Trp-AJa-Cys)-(Pr0)2-Lys-Asp-ß-Ala-Tyr-Gly-Arg-
(Lys)2-(Arg)s-Gln-(Arg)2-Nl-12; (SEQ ID NO:85)
AC-C( Cys-Glu-His-D-Z-N al-Arg-Trp-AJ a-Cys)- (Pro)_-Lys-Asp-ß-Ala-Tyr-Gly-Arg-
Cln-(Lys)2-(Arg)s-NHz; (SEQ ID NO:86)
AC-C(Cys-G] u -Hi s-D-2-Nal -A rg-Trp-A] a-Cys)-(Pr0)_-Lys-As p-ß-AIa-Ty r-Gly-A rg-
(Lys)2-(Arg)s-G1n-NH2; (SEQ TD NO:87)
AC-C(CyS-G1Li-His-D-2-NaI-Arg-1-Nal-AIa-Cys)-(Pr0)2-Lys-Asp-j3-Ala-Tyr-GIy-Arg-
(Lys)2-(Arg)2-GI'n-(Arg)3-NH2; (SEQ ID NO:71)
AC-C(Cys-Clu-His-D-2-N al-Arg-Bal-Ala-CyS)-(Pr0yi-Lys-Asp-jK-Ala-Tyr-Gly-Arg-
(Lys)2-(Arg)2-Gln-(Arg)a-NH:; (SEQ 1D NO:71)
Ac-C(Cys-Glu-His-D-Z-Nal-Arg-l-Nal-Ala-Cys)-(Pro)2-Lys-Asp-_]3-A1a- (Arg)2-Lys-
(Arg)z-Gln-(Arg)3-Nl-Iz; (SEQ ID NO:88)
AC*C(CYS*GIU*H isýDIZINaLArgýî *Nal *AI aýCys)ý(Pr0)2*LysýAspýßýA1aýArgýLysý
(Arg)3-G1n-(Arg)3-NH2; (SEQ ID NO:89)
AC-C(Cys-Ç]u-His-D-2-Nal-Arg-2-NaI-Ala-Cys)-(Pr0)2-Lys-Asp-ß-Ala- (Arg)2-Lys-
(Arg)2-G1n-(Arg)s-NH2; (SEQ ID NO:88)
AC-C(Cys-Glu-His-D-2-N al-Arg-Z-Nal-Ala-Cys)-(Pr0)2-Lys-Asp-ß-Ala-Tyr-Gly-(Arg)--
Lys-(Arg)2-Gln-(Arg)s-NHz; (SEQ 1D NO:90)
Ac-c(Cys-G1u-His-D-2-Nal-Arg-2-Nal-A1a-Cys)-(Pr0)2-Lys-Asp-_f3-Ala-Gly-(Arg)2-Lys-
(Arg)z-Gln-(Arg)s-NH:; (SEQ ID NO:91)
AC-C(CyS-G1Li-His-D-Z-Nal-Arg-2-Na]-AIa-Cys)-(Pro)2-Lys-Asp-ß-AIa-Gly-Arg-Lys-
(Arg)3-G]n-(Arg)s-NH2; (SEQ ID NO:92)
AC-C(Cys-Clu -Hi s-D-Z-Na l-Arg-î -NaI-Ala-Cys)-( Pr0)2-Lys-Asp-ß-AIa-Tyr-G Iy-(Arg)2-
Lys-(Arg)2-Gln-(Arg)a-NH2; (SEQ ID NO:95)
AC-C(Cys-GlLi-His-D-Z-NaI-Arg-1-Nal-AIa-Cys)-(Pr0)2-Lys-Asp-_ß-Ala-Tyr-Gly-Arg-
Lys-(Arg)3-Gln-(Arg)s-NI-Iz; (SEQ ID No:96)
AC-C(Cys-G1Li-His-D-2-NaI-Arg-1-Nal-A]a-Cys)-(Pr0)2-Lys-Asp-ß-AIa-GIy-(Arg)2-Lys-
(Arg)2-G1n-(Arg)3-NH2; (SEQ TD NO:97)
Ac-c(Cys-Glu-His-D-2-N al-Arö-l-N al-Ala-Cys)-(Pr0)2-Lys-Asp-ß-Ala-Gly-Arg-Lys-
(Arg)3-Cln-(Arg)3-NH2; (SEQ ID NO:92)
AC-C( Cys~Clu~His~D-2-N al-Arg-Z-N al-Ala-Cys)-(Pr0)z-Lys-Asp-_IÂ-Ala-(Arg)_-Lys-
(Arg)2-Gln-(Arg)3-N Hz; (SEQ ID NO:98)
AC-C(Cys-Clu-His-D-2-Na1-Arg-2-Na]-AIa-Cys)-(Pr0)2-Lys-Asp-j3-A]a-Arg-Lys-
(Arg)3-G1n-(Arg)3-NH2; (SEQ TD NO:99)
AC-C(Cys-G1Li-HiS-D-2-Nal-Arg-2-Na]-AIa-Cys)-(Pr0)2-Lys-Asp-j3-Ala-Tyr-GIy-Arg-
Lys-(Arg)3-G]h-(Arg)3-NH2; (SEQ ID No:101)
ACIC(CySIGluýHisýDIZINalýArgýBalýAlaICys)ý(Pro)2ýLysýASPIßýAlaý (Arg)2ýLysý
(Arg)--C1n-(Arg)3-NH:; (SEQ ID No:104)
Ac-c(Cys-Glu-His-D-Z-Nal-Arg-Bal-Ala-Cys)-(Pro)_-Lys-Asp-_ß-A1a-Arg-Lys-(Arg)3-
Gln-(Arg)s-N
AC-C(Cy5-GIu-His-D-2-Nal-Arg-Ba]-Ala-Cys)-(Pr0)2-Lys-Asp-_13-Ala-Tyr-CIy-(Arg)2-
Lys-(Arg)2-GIn-(Arg)3-NH2; (SEQ ID No:100)
AC-C(Cys-Glu -His-D-Z-Na I-Arg-Bal-AIa-Cys)-(Pr0)2-Lys-Asp-ß-Ala-Tyr-GIy-Arg-Lys-
(Arg)3-G1n-(Arg)3-NH2; (SEQ ID NO:101)
AC-C(Cys-Glu-His-D-2-Nal-Arö-Bal-Ala-Cys)-(Pr0)2-Lys-Asp-ß-Ala-Gly-(Arg)2-Lys-
(Arg):G1n-(Arg)3-NH:; (SEQ ID No:102)
Ac-c(Cys-Clu-His-D-Z-Nal-Arg-BaJ-Ala-Cys)-(Pro)2-Lys-Asp-_/3-A1a-Gly-Arg-Lys-
(Arg)3-Gln-(Arg)3-N
AC-C(Cys-G] u-Hi s-D-Z-Na 1 -A rg-T r p-A] a-Cys)-(Pr0)2-Lys-As p-ß-A] a-(Arg);-Gln-
(Arg)3-NH2; (SEQ TD No:113)
AC-C(Cys-GIu-His-D-2-Nal-Arg-Trp-Ala-Cys)-( Pr0)2-Arg-Asp±jX-Ala-(Arg)s-Gln-
(Arg)3-NH2; (SEQ 1D No:113)
AC-C(Cys-CI u -Hi s-D-2-Na1-Arg-Trp-AI a-Cys)- (Pr0)2-Lys-Asp-j3-A]a -Ty r-Cly-(Arg),=-
GI n-(Arg)3-N Hz; (SEQ [D No:114)
AC-C(Cys-ClLi-His-D-Z-NaI-Arg-Trp-A]a-Cys)-(Pr0)2-Arg-Asp-ß-Ala-Tyr-Cly-(Arg)s-
Glný(Arg)3ýNI-T2; (SEQ ID No:114)
AC-C(Cys-Clu-His~D-2-Nal-Arg-Trp-Ala-Cys)-(Pr0)2-Lys-ASp-ß-Ala-(Arg)s-Gln-
(Arg)4-NHz; (SEQ ID No:115)
AC-C(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Arg-A5p-jJ`-Ala-(Arg)5-Gln-
(Arg).i-NH2; (SEQ ID NO:115)
Ac-c(Cys-Glu-His-D-Z-Nal-Arg-Trp-Ala-Cys)-(Pro)i-Lys-Asp-jS-Ala-Tyr-Gly-(Arg)5-
Gln-(Arg)4-NH2; (SEQ ID No:116)
AC-C(Cys-G1Li-His-D-Z-NaI-Arg-Trp-A] a-Cys)-(Pr0)2-Arg-Asp-ß-Ala-Tyr-C1y-(Arg)s-
Gîn-(Arg)4-NH2; (SEQ ID No:116)
AC_C(Cys-Glu-His-D-2-NaI-Arg-1-Nal-A'a-CYS)-(Pr<-G]n-
(Arg)4-NH2; (SEQ ID No:118)
AC-c( Cys-Glu-His-D-Z-N al-Ar s-Gln-
(Arg)~±-NH:; (SEQ ID No:118)
Ac-C(Cys-C1u-His-D-2-Nal-Arg-1-Nal-Al a-Cys)-(Pro)--Arg-Asp-_IS-Ala-(Arg)o-Gln-
(Arg)3-NH2,' (SEQ ID No:119)
AC-C(Cys-Çlu-His-D-Z-Nal-Ai-g-î -Nal-A]a-Cys)-(Pr0)2-Lys-Asp-_IZ-Ala-Ty r-Çly-(Arg)s-
G]n-(Arg)3-NH2; (SEQ TD NO:120)
AC*C(CYS*GIU* HisýDIZINalýArgJ *NalýAl aICysy(Pro)2ýArgýAspýjJ*AlaýTyrýGlyý
(Arg)s-G1n-(Arg)3-NH2; (SEQ ID No:120)
AC-C(Cys-Glu-His-D-Z-Nal-Arg-l-Nal-Ala-Cys)-(Pr0)_-Lys-Asp-ß-Ala-Tyr-Gly-(Arg)5-
C1n-(Arg)4-NHz; (SEQ ID No:121)
Ac-C(Cys-Glu-I-Iis-D-Z-Nal-Arg-l-Nal-Ala-Cys)-(Pro)2-Arg-Asp-ß-Ala-Tyr-Gly-
(Arg)5-Gln-(Arg)4-NH2; (SEQ 1D No:121)
AC-C(Cys-C lu -Hi' S-D-Z-Na l-Arg-1 -Nal-Ala-Cys)-( Pr0)2-Lys-Asp-ß-Ala-Tyr-G ly-(Argyi-
G]n-(Arg)a-NH2; (SEQ TD No:122)
AC-C(Cys-Glu-His-D-Z-Nal-Arg-î -Nal -Al a-Cys)-(P ro)2-Arg-Asp-_ß-AIa-Tyr-Gly-
(Arg)ß-Gln-(Arg)3-NI-L; (SEQ ID NO:122)
AC-C(Cys-G]Li-His-D-Z-NaI-Arg-2-Na1-AIa-Cys)-(Pr0)z-Arg-Asp-ß-A]a-(Arg)«-Gln-
(Arg)3-NH2; (SEQ ID No:124)
AC-C(Cys-Glu-His-D-2-Nal-Arg-Z-N al-Ala-Cys)-(Pr0)2-Lys-Asp-ß-Ala-(Arg)5-Gln-
(Arg)+-NI-Iz; (SEQ ID No:125)
AC-C( CyS-Clu-His-D-Z-N al-Arg-Z-N al-Al a-Cys)-(Pro)_-Ar g-Asp-ß-Ala-(Ar g)s-Cln-
AC-C(Cys-C] u -Hi s-D-2-Na1 -A rg-Z-NaI-Al a -Cys)-(Pr0)2-Lys-Asp7/3-A1;i-T}r r-Cly-(Arg)s-
G]n-(Arg)3-NH2; (SEQ TD No:126)
AC-C(CyS-GIu-H is-D-Z-Nal-Arg-Z-Na] -Al a-Cys)-(P r0)2-Arg-Asp-ß-AIa-Tyr-Gly-
(Arg)5-G1n-(Arg)3-NH2; (SEQ ID No:126)
AC*C(CyS*GJuIHISIDý2ýN alýArgIZINalýAlaýCys)I(PI0)2ILysýAspýßýAlaýTyrýGlyý(Arg)eý
Gln-(Arg)3-NI-Iz; (SEQ ID No:127)
Ac-c(Cys-Glu-His-D-Z-Nal-Arg-Z-Nal-Ala-Cys)-(Pro)2-Arg-Asp-ß-Ala-Tyr-Gly-
(Arg)e-Gln-(Arg)a-NH2; (SEQ 1D N 02127)
AC-C(Cys-C1 u -Hi s-D-2-Na1-Arg-2-Nal-A1a-Cys)-(Pro)2-Lys-Asp-ß-A1a-Ty r-Gly-(A r g):-
Gln-(Arg)4-NH2; (SEQ ID No:128)
AC-C(Cys-Glu - His-D-Z-NaI-Arg-Z-Nal-Al a-Cys)-(Pro):-Arg-Asp-_13-Ala-Tyr-Gly-
(Arg)s-G1n-(Arg)4-NH2; (SEQ TD No:128)
AC-c(Cys-Glu-His-D-2-Nal-Arg-Bal-AJa-Cys)-(Pr0)2-Lys-Asp-ß-Ala-(Arg)s-Gln-
(Arg)4-NHz; (SEQ ID No:130)
Ac-c(Cys-C]u-His-D-2-Na1-Arg-Bal-Ala-Cys)-(Pro)_-Arg-Asp-ß-Ala-(Arg)s-Gln-
(Arg)4-NH2; (SEQ ID No:130)
AC-C(Cys-G]u-His-D-Z-Na]-Arg-BaI-AIa-Cys)-(Pr0)2-Arg-Asp-ß-AIa-'T'y r-GIy-(Arg)a-
G]n-(Arg)3-NH2; (SEQ ID No:133)
AC-C(Cys-Glu-His-D-Z-NaI-Arg-BaI-Ala-Cys)-(Pr0)2-Lys-A5p-j›'-AIa-Tyr-Gly-(Arg)s-
G]ri-(Arg)4-NH2; (SEQ TD No:134)
AC-C(CyS-G]Li-His-D-Z-Na]-Arg-BaI-AIa-Cys)-(Pr0)2-Arg-Asp-ß-AIa-Tyr-CIy-(Arg);-
Glri-(Arg).i-NHz; (SEQ ID No:134)
AC-C(Cys-GIu-His-D-2-Nal-Arg-Ba]-Ala-Cys)-(Pr0)2-Lys-Asp-_13-Ala-Tyr-GIy-(Arg)h-
G]n-(Arg)3-NH2; (SEQ TD No:135)
Ac-C(Cys-GJu-His-D-2-N al-Arg-Bal-Ala-Cys)-(Pr0)2-Arg-Asp-ß-Ala-Tyr-Gly-(Arg)a-
Gln-(Arg)s-Nl-l2; (SEQ 1D NO:135)
AC-Nle-C(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(DOC)2-Tyr-Gly-Arg-(Lys)2-(Arg)--Gln-
(Arg)3-NI-Iz; (SEQ ID No:136)
AC-N]e-C(Cys-D-A1a-Hîs-D-Phe-Arg-Trp-Cys)-j.s`-A] a-Tyr-Gly-Arg-(Lys)2-Arg-Gln-
(Arg)4-NH2; (SEQ TD No:137)
AC-NIe-C(Cys-D-A]a-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-C]y-Arg-(Lys)2-(Arg)2-GIn-
(Arg)3-NH2; (SEQ ID No:136)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-ß-Ala-(Arg)5-Gln-(Arg)3-NHz; (SEO ID No:138)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-ß-Ala-GIy-(Arg)5-Gln-(Arg)3-NH2; (SEO ID No:138)
Ac-Nle-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-ß-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (SEO ID No:139)
Ac-Nle-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-ß-Ala-GIy-(Arg)5-Gln-(Arg)4-NH2; (SEO ID No:140)
Ac-N]e-C(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-j3-A1a-Tyr-Gly-(Arg)2-Lys-(Arg)z-G]ri-
(Arg)3-NH2; (SEQ 1D No:141)
AC-Nl e-C(Cys-D-A1 a-Hi' s-D-Phe-Arg-Trp-Cys)-j3-A1 a-Tyr-GIy-Arg-Lys-(Arg)3-Gln-
(Arg)3-NH:; (SEQ ID No:142)
AC-N le-C(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-_]3-Ala-Gly-(Arg)2-Lys-(Arg)2-Gln-
(Arg)3-NI-Iz; (SEQ ID NO:141)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-ß-A1a-Gly-Arg-Lys-(Arg)a-Gln-(Arg)3-
NH2; (SEQ [D No:142)
AC-Nle-C(Cys-D-Ala-His-D-Phe-Arg-Trp-Cy5)-j3-A1a- (Arg)2-Lys-(Arg)2-G1n-(Arg)3-
NHi; (SEQ ID No:143)
Ac-Nle-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-ß-Ala-Arg-Lys-(Arg)3-GIn-(Arg)3-NHz; (SEO ID No:144)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-ß-Ala-(Arg)5-GIn-(Arg)3-NHz; (SEO ID No:148)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(ß-Ala)2-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:148)
Ac-Nle-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-(ß-Ala)2-GIy-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:149):
AC-Nle-C(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(]3-Ala)2- yr-Gly-(Arg)a-Gln-(Arg)3-
NHz; (SEQ 1D No:149)
Ac-Nle-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:151)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-GIy-(Arg)5-Gln-(Arg)3-NH2; (SEO ID No:150)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-GIy-(Arg)5-Gln-(Arg)3-NH2; (SEO ID No:150)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2; (SEO ID No:151)
AC-Nle-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-(Doc)2-GIy-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:152)
Ac-Nle-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (SEO ID No:152)
Ac-Nle-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-ß-Ala-(Arg)5-GIn-(Arg)4-NHz; (SEO ID No:154)
Ac-Nle-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-,ß-Ala-Tyr-Gly-(Arg)5-GIn-(Arg)4-NHz; (SEO ID No:153)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(ß-Ala)2-(Arg)5-GIn-(Arg)4-NH2; (SEO ID No:154)
Ac-Nle-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-(ß-Ala)2-GIy-(Arg)5-GIn-(Arg)4-NH2; (SEO ID No:155)
AC-NIe-C(Cys-D-A]a-His-D-Phe-Arg-Trp-Cys)-(ß-Ala)2-Tyr-CIy-(Arg)a-Cln-(Arg)4-
NI-Ii; (SEQ ID No:155)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-G|n-(Arg)4-NH2; (SEO ID No:157)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Gly-(Arg)5-G|n-(Arg)4-NH2; (SEO ID No:156)
Ac-Nle-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-D0c-Tyr-GIy-(Arg)5-Gln-(Arg)4-NH2; (SEO ID No:156)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2; (SEO ID NO:15?)
Ac-Nle-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-(Doc)2-GIy-(Arg)5-Gln-(Arg)4-NH2; (SEO ID No:158)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (SEO ID No:158)
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-ß-AIa-Tyr-GIy-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:159)
AC-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-ß-AIa-(Arg)s-GIn-(Ar
Ac-Nle-C(Asp-His-D-Phe-Arg-Trp-AIa-Lys)-ß-AIa-Tyr-Gly-(Arg)5-GIn-(Arg)3-NHZ; (SEO ID No:161)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-AIa-Lys)-ß-Ala-(Arg)5-Gln-(Arg)3-NHZ; (SEO ID No:162)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-ß-Ala-Tyr-GIy-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:164)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-ß-Ala-GIy-(Arg)5-GIn-(Arg)3-NHz; (SEO ID No:163)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-ß-Ala-(Arg)5-GIn-(Arg)3-NHz; (SEO ID No:163)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(ß-Ala)2-Tyr-GIy-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:164)
Ac-Nle-c(Asp-His-D-Phe-Arg-Ti'p-Lys) (ß-Ala)2-Gly-(Arg)5-Gln-(Arg)3-NH2; (SEO ID No:165)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys) (ß-Ala)2-(Arg)5-GIn-(Arg)3-NHz; (SEO ID No:165)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys) Doc-Tyr-Gly-(Arg)5-GIn-(Arg)3-NHz; (SEO ID No:166)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys) Doc-GIy-(Arg)5-Gln-(Arg)3-NH2; (SEO lD No:166)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys) Doc-(Arg)5-Gln-(Arg)3-NH2; (SEO ID No:168)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys) (Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (SEO ID No:167)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys) (Doc)2-GIy-(Arg)5-Gln-(Arg)3-NH2; (SEO lD NO:16?)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys) (Doc)2-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:168)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-ß-Ala-Tyr-GIy-(Arg)5-G|n-(Arg)4-NHz; (SEO ID No:170)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-ß-Ala-GIy-(Arg)5-GIn-(Arg)4-NHz; (SEO ID No:169)
AC-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-ß-Ala-(Arg)5-GIn-(Arg)4-NHz; (SEO ID No:169)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(ß-Ala)2-Tyr-GIy-(Arg)5-GIn-(Arg)4-NH2; (SEO ID No:170)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(ß-Ala)2-GIy-(Arg)5-G|n-(Arg)4-NH2; (SEO ID No:171)
Ac-N le-c(Asp-His-D-Phe-Arg-Trp-Lys
AC-Nle-C(Asp-His-D-Phe-Arg-Trp-Lys)-DOC-Tyr-GIy-(Arg)5-GIn-(Arg)4-NH2; (SEO ID No:173)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-GIy-(Arg)5-Gln-(Arg)4-NH2; (SEO lD No:172)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-(Arg)5-Gln-(Arg)4-NH2; (SEO ID No:172)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-Tyr-GIy-(Arg)5-Gln-(Arg)4-NH2; (SEO ID No:173)
AC-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-GIy-(Arg)5-Gln-(Arg)4-NH2; (SEO ID No:174)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-(Arg)5-GIn-(Arg)4-NH2; (SEO ID No:174)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-ß-AIa-Lys)-ß-AIa-Tyr-GIy-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:175)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-ß-AIa-Lys)-ß-AIa-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:176)
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-ß-AIa-Tyr-GIy-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:177)
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-ß-AIa-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:178)
D-Phe-C(Cys-His-D-Phe-Arg-Trp-ß-AIa-D-Cys)-Thr-j3-AIa-Tyr-GIy-(Arg)s-CIn-(Arg)s-
NI-Ii; (SEQ ID No:179)
D-Phe-c(Cys-His-D-Phe-Arg-Trp-ß-Ala-D-Cys)-Thr-ß-AIa-(Arg)5-GIn-(Arg)3-NHz; (SEO ID No:180)
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-ß-AIa-Tyr-GIy-(Arg)5-GIn-(Arg)3-NHz; (SEO ID No:181)
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-,B-AIa-(Arg)5-GIn-(Arg)3-NHZ; (SEO ID No:182)
Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-ß-Ala-Tyr-GIy-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:183)
AC-Cha-C(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-ß-AIa-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:184)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-ß-AIa-Tyr-GIy-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:183)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-ß-AIa-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:185)
AC-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-ß-Ala-Tyr-GIy-(Arg)s-GIn-(Ar
Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-ß-AIa-(Arg)s-GIn-(Arg)3-NH2; (SEO ID No:185)
AC-hCha-C(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-ß-Ala-Tyr-Gly-(Arg)s-Gln-(Arg)s-
NHi; (SEQ ID No:186)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-ß-Ala-(Arg)s-Gln-(Arg)3-NHz; (SEO ID No:188)
AC-hCha-C(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(IS-A1a)2-Tyr-Gly-(Arg)s-Gln-(Arg)3-
NHz; (SEQ ID No:187)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(ß-Ala)2-(Arg)5-Gln-(Arg)3-NH2; (SEO ID No:188)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-D0c-Tyr-GIy-(Arg)5-Gln-(Arg)3-NH2; (SEO ID No:189)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-(Arg)5-Gln-(Arg)3-NH2; (SEO lD No:190)
AC-hCha-C(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(D0C)2-Tyr-Gly-(Arg)5-GIn-(Arg)s-
NHz; (SEQ ID No:189)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2; (SEO ID No:190)
ACIhChaIC(AspýHisýDýPheýArgýTrpýGabaýLys)ý_ßýAlaýTyrýGlyý(Arg)sýG1ný(Arg)4ý
NH2; (SEQ ID No:191)
Ac-hCha-C(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-ß-Ala-(Arg)5-Gln-(Arg)4-NH2; (SEO ID No:192)
Acýh Cha*c(AspýHisýDýPheýArgýTrpýGaba*Lys)ý(ßýA1a)2ýTyrýGlyý(Arg)sýG]ný(Arg)4ý
NH2; (SEQ ID No:191)
Ac-hCha-C(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(ß-Ala)2-(Arg)5-Gln-(Arg)4-NHz; (SEQ lD No:192)
Ac-hCha-C(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (SEQ ID No:193)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-(Arg)5-GIn-(Arg)4-NH2; (SEQ lD No:194)
Ac-h Cha-C(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(Doc)2-Tyr-GIy-(Arg).=-GIn-(Arg)4-
NHz; (SEQ ID No:193)
Ac-hCha-C(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(Doc)2-(Arg)5-Gln-(Arg)4-NHz; (SEQ ID No:194)
Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys):ß-Ala-Tyr-GIy-(Arg)s-Gln-(Arg)s-
NHz; (SEQ ID No:195)
Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-,ß-Ala-(Arg)5-Gln-(Arg)3-NH2; (SEQ ID No:196)
Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-ß-Ala-Tyr-GIy-(Arg)5-GIn-(Arg)3-NH2; (SEQ ID NO:19?)
Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-ß-Ala-(Arg)5-GIn-(Arg)3-NHz; (SEQ ID No:198)
AC-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Apn-Cys)-ß-Ala-Tyr-Gly-(Arg)5-Cln-(Arg)a-
NI-Ii; (SEQ ID No:199)
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Apn-Cys)-ß-AIa-(Ar
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-ß-AIa-Tyr-GIy-(Arg)5-GIn-(Arg)3-NH2; (SEQ ID No:199)
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-ß-Ala-(Arg)5-GIn-(Arg)3-NH2; (SEQ ID No:200)
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-ß-Ala-Cys)-ß-Ala-Tyr-Gly-(Arg)5-GIn-(Arg)3 NH2; (SEQ ID No:201)
AC-Nle-c(Cys-His-D-Phe-Arg-D-Trp-ß-AIa-Cys)-ß-A|a-(Arg)5-G|n-(Arg)3-NHz; (SEQ ID No:202)
Ac-Nle-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Pen)-ß-AIa-Tyr-GIy-(Arg)5-Gln-(Arg)3-NHz; (SEQ ID No:203)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-ß-Ala-GIy-(Arg)5-Gln-(Arg)3-NHz; (SEQ ID No:203)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-ß-Ala-(AI'
AC-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(fî-A1a)2-Tyr-Gly-(Arg)s-Gln-(Arg)a-
NH2; (SEQ ID No:204)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(ß-Ala)2-Gly-(Arg)5-GIn-(Arg)3-NHz; (SEQ ID No:204)
Ac-Nle-C(Cys-D-AIa-His-D-Phe-Arg-Trp-Pen)-(ß-Ala)2-(Arg)5-GIn-(Arg)3-NHz; (SEQ lD No:205)
Ac-Nle-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Pen)-Doc-Tyr-GIy-(Arg)5-GIn-(Arg)3-NHz; (SEQ ID NO:20?)
Ac-Nle-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Pen)-Doc-GIy-(Arg)5-GIn-(Arg)3-NH2; (SEQ ID No:206)
AC-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-Doc-(Arg)5-GIn-(Arg)3-NHz; (SEQ ID No:206)
AC-Nle-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Pen)-(Doc)2-Tyr-GIy-(Arg)5-GIn-(Arg)3-NH2; (SEQ ID No:207)
AC-Nle-C(Cys-D-AIa-His-D-Phe-Arg-Trp-Pen)-(Doc)2-Gly-(Arg)5-Gln-(Arg)3-NH2; (SEQ ID No:208)
Ac-Nle-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Pen)-(Doc)2-(Arg)5-GIn-(Arg)3-NHz; (SEQ ID No:208)
D-Phe-C(Cys-His-D-(Et)Tyr-Arg-Trp-j3-A1a-D-Cys)-j3-A1a-Tyr-Cly-(Arg)5-Cln-(Arg)3-
NHz; (SEQ ID No:209)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-ß-AIa-D-Cys)-ß-AIa-(Arg)5-Gln-(Arg)3-NHz; (SEQ ID No:210)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-ß-Ala-D-Cys)-ß-AIa-GIy-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:209)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-ß-Ala-D-Cys)-ß-AIa-(Arg)5-GIn-(Arg)4-NHz; (SEO ID No:211)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-ß-AJa-D-Cys)-(ß-Ala)2-Tyr-Gly-(Arg)s-Gln-
(Arg)3-NH2; (SEQ ID No:212)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-ß-AIa-D-Cys)-(ß-A|a)2-(A|'g)s-G|n-(Arg)3-NHz; (SEO ID No:213)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-ß-Ala-D-Cys)-UZ-Ala)2-Gly-(Arg)5-Gln-(Arg)3-
NHi; (SEQ [D No:213)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-ß-Ala-D-Cys)-(ß-Ala)2-(Arg)5-Gln-(Arg)4-NHz; (SEO ID NO:26?)
D-Phe-C(Cys-His-D-(Et)Tyr-Arg-Trp-ß-Ala-D-Cys)-D0C-Tyr-G1y-(Arg)5-Gln-(Arg)3-
NHi; (SEQ [D No:214)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-ß-Ala-D-Cys)-D0c-(Arg)5-GIn-(Arg)3-NHz; (SEO ID No:216)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-ß-AIa-D-Cys)-Doc-Gly-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:214)
D-Phe-C(Cys-HiS-D-(Et)Tyr-Arg-Trp-ß-Ala-D-Cy5)-Doc-(Arg)5-GIn-(Arg)4-NH2; (SEO ID NO:21?)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-j3-Ala-D-Cys)-(D0C)2-Tyr-Gly-(Arg)5-C]n-(Arg)3-
NH2; (SEQ [D No:215)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-ß-Ala-D-Cys)-(Doc)2-(Arg)5-GIn-(Arg)3-NHz; (SEO ID No:216)
D-Phe-C(Cys-His-D-(Et)Tyr-Arg-Trp-ß-Ala-D-Cys)-(D0c)2-Gly-(Arg)5-Gln-(Arg)a-
NHz; (SEQ ID No:215)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-ß-Ala-D-Cys)-(D0c)2-(Arg)5-GIn-(Arg)4-NHz; (SEO ID NO:21?)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-ß-Ala-D-CysyThrß-Ala-Tyr-Gly-(Arg)5-Gln-
(Arg)3-NH2; (SEQ ID No:218)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-ß-Ala-D-Cys)-Thrîß-Ala-(Arg)s-G1n-(Arg)a-
NHz; (SEQ ID No:219)
D-Phe-C(Cys-His-D-(Et)Tyr-hArg-Trp-ß-Ala-D-Cys)-Thr-(jî-Alap-Tyr-Cly-(Arg)5-Cln-
(Arg)3-NH2; (SEQ ID No:218)
D- Ph e-C(Cys-Hi s-D-(Et)Tyr-h Arg-Trp-ß-Al a -D-Cys)-Thr-(ß-AI a)2-(Arg)s-G In -(Arg)s-
NHz; (SEQ ID No:219)
D-Phe-C(CyS-His-D-(Et)Tyr-hArg-Trp-ß-A]a-D-Cys)-Th r-DOC-Tyr-GIy-(Arg)s-G1n-
(Arg)3-NH2; (SEQ 1D No:221)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-ß-AIa-D-Cys)-Thr-Doc-(Arg)5-Gln-(Arg)3-NH2; (SEO ID No:220)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-jZ-Ala-D-Cys)-Thr-(D0c)2-Tyr-Gly-(Arg)5-Gln-
(Arg)3-Nl-12; (SEQ 1D No:221)
D-Phe-C(Cys-His-D-(Et)Tyr-hArg-Trp-ß-Ala-D-Cys)-Thr-ß-A1a-Tyr-C1y-(Arg)5-G1n-
(Arg)4-NH2; (SEQ ID No:222)
D-Ph e-C(Cys- Hi s-D-(Et)Tyr-hArg-Trp-ß-Al a-D-Cys)-Thr-ß-Al a-(Arg)5-Gln-(Arg)4-
NHz; (SEQ ID No:223)
DýPh 8*C(C)TSIHI sýDý(Et)TyrýhArgýT r pýßýA] aýDýCysyTh r* (fîýAl a )2ýTyrýGIyý(A I'g)5*G] n*
(Arg)4-NHz; (SEQ ID NO:222)
D-Phe-C(Cys-His-D-(Et)Tyr-hArg-Trp-ß-A1a-D-Cys)-Thr-(IS-Ala)2-(Arg)s-Gln-(Arg)4-
NHz; (SEQ ID No:223)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-ß-Ala-D-CysyThr-Doc-Tyr-Gly-(Arg)s-Cln-
(Arg)4-NH2; (SEQ ID No:224)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-ß-AIa-D-Cys)-Thr-Doc-(Arg)5-G|n-(Arg)4-NH2; (SEO ID No:225)
D-Phe-C(Cys-His-D-(Et)Tyr-hArg-Trp-ß-A1a-D-Cys)-Thr-(Doc)2-Tyr-G]y-(Arg)s-G]n-
(Arg)4-NHz; (SEQ ID No:224)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-j$-Ala-D-Cy3)-Thr-(D0c)z-(Arg)s-Gh1-(Arg)4-
NHz; (SEQ ID No:225)
D-Phe-c(Cys-l-lis-D-(Et)Tyr-hArg-Bip-_ß-Ala-D-Cys)-Thr-j3-Ala-Tyr-Gly-(Arg)s-Gln-
(Arg)3-NH2; (SEQ TD No:227)
D-Ph e-c(Cys-Hi s-D-(Et)Ty r-hArg-B i p-ß-A] a-D-Cys)-Th r-ß-A] a-Ty r-Gly-(A rg)s-GI ri-
(Arg)+-NH2; (SEQ 1D No:226)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-jK-Ala-D-Cys)-Thr-ß-Ala-(Arg)5-Gln-(Arg)3-
NHi; (SEQ [D No:228)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-ß-AJa-D-Cys)-Thr-(IS-Ala)2-Tyr-Gly-(Arg)5-Gln-
(Arg)3-NI-Iz; (SEQ ID No:227)
D-Phe-C(Cys-His-D-(Et)Tyr-hArg-Bip-_ß-Ala-D-Cy5)-'I'hr-(ß-A1a)2-(Arg)5-G1n-(Arg)3-
NH2; (SEQ ID No:228)
DýPheýc(CysýHisýDý(Et)TyrýhArg*BipýfiîAlaýDýCys)ýThrýD0cýTyrýGlyý(Arg)5*Glný
(Arg)3-NI-Iz; (SEQ ID No:229)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-jS-Ala-D-Cy5)-Thr-Doc-Tyr-G1y-(Arg)5-Gln-
(Arg)4-NH2; (SEQ ID No:230)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-ß-AIa-D-Cys)-Thr-Doc-(Arg)5-GIn-(Arg)3-NHz; (SEO ID No:232)
D-Phe-C(Cys-HiS-D-(Et)Tyr-hArg-Bip-ß-Ala-D-CyS)-Thr-(DOC)2-Tyr-Gly-(Arg)s-Gln-
(Arg)3-NH2; (SEQ TD No:231)
DýPheýc(CysýHisýD*(Et)TyrýhArgIBipýßýAlaýDICy8)*Thrý(D0C)2ý(Arg)5ýGlriý(Arg)3ý
NHz; (SEQ ID No:232)
AC-Nle-C(Cys-D-Ala-His-D-Phe-Arg-Trp-Gly-Cys)-_[3-Ala-Tyr-Gly-(Arg)s-G1n-(Arg)a-
Nl-h; (SEQ [D No:233)
AC-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gly-Cys)-ß-Ala-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:234)
NIe-C(CyS-His-D-Phe-Arg-Trp-Apn-Cys)-ß-AIa-Tyr-Gly-(Arg)5-GIn-(Arg)3-NHz; (SEQ ID No:235)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys -ß-AIa-(Arg)5-GIn-(Arg)3-NHz; (SEO ID No:236)
NIe-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys -(ß-Ala)2-Tyr-GIy-(Arg)5_Gln-(Arg)3-NHz; (SEO ID No:235)
NIe-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys -(ß-Ala)2-(Arg)5-GIn-(Arg)3-NHZ; (SEO ID No:236)
Nle-C(Cys-His-D-Phe-Arg-Trp-Apn-Cys -ß-AIa-Tyr-Gly-(Arg)5-GIn-(Arg)4-NHz; (SEO ID NO:23?)
NIe-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys -ß-AIa-(Arg)5-GIn-(Arg)4-NHz; (SEO ID No:238)
NIe-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys -(ß-Ala)2-Tyr-GIy-(Arg)5-GIn-(Arg)4-NHZ; (SEO ID NO:23?)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys -(ß-Ala)2-(Arg)5-GIn-(Arg)4-NHz; (SEO ID No:238)
NIe-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys -Doc-Tyr-GIy-(Arg)5-GIn-(Arg)3-NHZ; (SEO ID No:239)
NIe-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys -Doc-(Arg)5-G|n-(Arg)3-NH2; (SEO ID No:240)
NIe-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys -(D0c)2-Tyr-GIy-(Arg)5-GIn-(Arg)3-NHz; (SEO lD No:239)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys -(Doc)2-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:240)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys -Doc-Tyr-GIy-(Arg)5-G|n-(Arg)4-NHz; (SEO ID No:241)
NIe-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys -Doc-(Arg)5-Gln-(Arg)4-NH2; (SEO ID No:242)
NIe-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys -(D0c)2-Tyr-GIy-(Arg)5-GIn-(Arg)4-NHz; (SEO ID No:241)
NIe-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(Doc)2-(Arg)5-GIn-(Arg)4-NH2; (SEO ID No:242)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-ß-AIa-Tyr-GIy-(Arg)5-G|n-(Arg)3-NHz; (SEO ID No:243)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-ß-Ala-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:244)
AC-N Ie-C(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)- (ß-AI a)2-Tyr-GIy-(Arg)a-GIn-(Arg)3-
NHz; (SEQ ID No:243)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(ß-Ala)2-(Arg)5-GIn-(Arg)3-NHz; (SEO ID No:244)
AC-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-GIy-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:245)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-GIn-(Arg)3-NHZ; (SEO lD No:246)
AcýNleýc(CysýDýLeu*HisýDýPheýArgýTrpýCyS)*(Doc)2ýTyrýG]yý(Arg)sýG]ri*(Arg)sý
NHz; (SEQ ID NO:245)
AC-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-GIn-(Arg)3-NHz; (SEO ID No:246)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-ß-AIa-Tyr-GIy-(Arg)5-Gln-(Arg)4-NHz; (SEO ID No:247)
AC-Nle-C(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-ß-Ala-(Arg)5-Gln-(Arg)4-NH2; (SEO ID No:248)
AC-N Ie-C(Cys-D- Leu -Hi s-D-Ph e-Arg-Trp-Cys)- (ß-AI a )2-Tyr-Gly-(Arg)s-Gln -(Arg)4-
NHz; (SEQ ID No:247)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(ß-Ala)2-(Arg)5-GIn-(Arg)4-NH2; (SEO ID No:248)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-GIy-(Arg)5-Gln-(Arg)4-NH2; (SEO lD No:249)
AC-Nle-C(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-Gln-(Arg)4-NHz; (SEO ID No:250)
Ac-Nle-C(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(D0c)2-Tyr-Gly-(Argß-Gln-(Argh-
NHz; (SEQ ID No:249)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-GIn-(Arg)4-NHz; (SEO ID No:250)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-ß-AIa-Tyr-GIy-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:251)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-ß-Ala-(Arg)5-G|n-(Arg)3-NH2; (SEO ID No:252)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(ß-Ala)2-Tyr-Gly-(Arg)s-G]n-(Arg)3-
NHz; (SEQ ID No:251)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(ß-Ala)2-(Arg)5-Gln-(Arg)3-NHz; (SEO lD No:252)
AC-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-GIy-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:253)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:254)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-GIy-(Arg)5-GIn-(Arg)3-NHz; (SEO ID No:253)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:254)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-ß-AIa-Tyr-GIy-(Arg)5-Gln-(Arg)4-NHz; (SEO ID No:255)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-ß-AIa-(Arg)5-GIn-(Arg)4-NH2; (SEO ID No:256)
AC-NIe-C(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(ß-Ala)2-Tyr-Cly-(Arg)s-GIn-(Arg)4-
Nm› (SEQ ID No:255)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(ß-Ala)2-(Arg)5-GIn-(Arg)4-NHz; (SEO ID No:256)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-GIy-(Arg)5-GIn-(Arg)4-NH2; (SEO ID No:257)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-GIn-(Arg)4-NH2; (SEO ID No:258)
AC-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(D0c)z-Tyr-Gly-(Arg)s-Gln-(Arg)4-
NHz; (SEQ [D No:257)
AC-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-GIn-(Arg)4-NH2; (SEO ID No:258)
NIe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-ß-AIa-Tyr-GIy-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:259)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-ß-Ala-(Arg)5-Gln-(Arg)3-NHz; (SEO ID No:260)
NIe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(ß-Ala)2-Tyr-GIy-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:259)
NIe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(ß-Ala)2-(Arg)5-GIn-(Arg)3-NHz; (SEO ID No:260)
N[e-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-ß-AIa-Tyr-GIy-(Arg)5-GIn-(Arg)4-NH2; (SEO ID No:261)
N[e-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-ß-AIa-(Arg)5-GIn-(Arg)4-NHz; (SEO ID No:262)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(ß-Ala)2-Tyr-GIy-(Arg)5-GIn-(Arg)4-NH2; (SEO ID No:261)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(ß-Ala)2-(Arg)5-GIn-(Arg)4-NH2; (SEO ID No:262)
Nle-C(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-Doc-Tyr-Gly-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:263)
N[e-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-Doc-(Arg)5-Gln-(Arg)3-NH2; (SEO ID No:264)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2; (SEO ID No:263)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(D0c)2-(Arg)5-GIn-(Arg)3-NH2; (SEO ID No:264)
Nle-C(CyS-His-D-Phe-Arg-Trp-Gaba-Cys)-DOC-Tyr-Gly-(Arg)5-GIn-(Arg)4-NH2; (SEO ID No:265)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-Doc-(Arg)5-Gln-(Arg)4-NH2; (SEO ID No:266)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2; (SEO ID No:265)
N[e-C(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)2-(Arg)5-G|n-(Arg)4-NH2; (SEO ID No:266)
AC-C(Cys-Glu-His-D-4-Br-Phe-Arg-Trp-GIy-Cys)-(Pr
Ac-c(Cys-Glu-His-D-2-NaI-Arg-Trp-AIa-Cys)-(Pr
Ac-c(Cys-Glu-His-D-2-NaI-Arg-2-Nal-AIa-Cys)-(Pr
Ac-c(Cys-Glu-His-D-2-NaI-Arg-1-Nal-AIa-Cys)-(Pr
AC-C(Cys-Glu-His-D-2-NaI-Arg-BaI-AIa-Cys)-(Pro)2-Lys-Asp-NH2; (SEO ID No:269)
Ac-c(Cys-Glu-His-D-2-NaI-Arg-2-Nal-ß-AIa-Cys)-(Pro)2-Lys-Asp-NHz; (SEO ID No:270)
Ac-c(Cys-Glu-His-D-2-NaI-Arg-2-Nal-Aib-Cys)-(Pr
c[Hydantoin(C(O)-(Cys-D-AIa))-His-D-Phe-Arg-Trp-Cy51-NHz; (SEO lD No:271)
c[Hydantoin(C(O )- (hCys-D-Ala))-His-D-Phe-Arg-Trp-Cys]-NHz; (SEO ID No:271)
c[Hydantoin(C(O)- (Cys- -D -Ala))- His- D- 2- Nal- -A-rg-Trp Cys]- -NH2; (SEO ID NO: 272)
c[Hydantoin(C(O)- (hCys- -D- -A-Ia)) -His- D- 2- Nal- -Arg-Trp- Cys]- NH2; (SEO ID NO: 272)
c[Hydantoin(C(O)- (Asp- -D A-Ia))- -His- D- Phe- --Arg Trp- Lys]- NH2; (SEO ID NO: 273)
c[Hydantoin(C(O)- (Asp-D -A|a))- His- D- Phe- -A-rg -Trp-Orn]- NH2; (SEO ID NO: 273)
c[Hydantoin(C(O)- (Asp- D- -A-Ia)) His- D- Phe- -Arg- Trp- Dab]- -NH2; (SEO ID NO: 273)
c[Hydantoin(C(O)- (Asp- D-Ala))- His- D- Phe- --Arg Trp- Dap]- -NH2; (SEO ID NO: 273)
c[Hydantoin(C(O)- (Asp- His))- -D- 2- -N-al-Arg Trp- Lys]- NHZ; (SEO ID NO: 275)
c[Hydantoin(C(O)- (Asp- His))- D-Phe-Arg-Trp-Lys]-NH2; (SEO ID No:274)
c[Hydantoin(C(O)- (Asp- A30))- D- P-h-e-Arg-Trp Lys]- NH2; (SEO ID NO: 274)
c[Hydantoin(C(O)- -(-Asp -A-50)) D- P-he-Arg-Trp Lys]- NH2; (SEO ID NO: 274)
c[Hydantoin(C(O)- (Asp- Aöc))- -D- --Phe-Arg-Trp Lys]- N-Hz; (SEO ID NO: 274)
c[Hydantoin(C(O)- (Asp-A3c))- D- 2- Nal- -A-rg Trp- Lys]- -NH2; (SEO ID NO: 275)
c[Hydantoin(C(O)- (Asp- A50))- D- 2- Nal- -Arg- Trp- Lys]- -NH2; (SEO ID NO: 275)
c[Hydantoin(C(O)- (Asp- A60))- D- 2- Nal- -Arg- Trp- Lys]- NH2; (SEO ID NO: 275)
c[Hydantoin(C(O)- (Asp- A5c))- D- 2- Nal- -Arg- Trp- Lys]- NH2; (SEO ID NO: 275)
c[Hydantoin(C(O)- (Asp-Aic))- D- Phe-Arg-Trp- Lys]- NH2; (SEO ID NO: 274)
c[Hydantoin(C(O)- -(-Asp Apc))- D- -P-he-Arg-Trp Lys]- NH2; (SEO ID NO: 274)
c[Hydantoin(C(O)- (Asp- Aic))- --D 2- Nal- -A-rg-Trp Lys]- -NH2; (SEO ID NO: 275)
c[Hydantoin(C(O)- (Asp- Apc))- D- 2- Nal- -Arg- Trp- Lys]- -NH2; (SEO ID NO: 275)
C[Hydantoin-(C(O)-(Asp-Aic))-D-2-Nal-Arg-Trp-Lys]-NHz; (SEO ID No:275)
c[Hydantoin-(C(O)-(Asp-Apc))-D-2-Nal-Arg-Trp-Lys]-NHz; (SEO ID No:275)
c[Hydantoin(C(O)-(Glu-D-Ala))-His-D-Phe-Arg-Trp-Orn]-NHz; (SEO ID No:276)
c[Hydantoin(C(O)-(GIu-D-Ala))-His-D-Phe-Arg-Trp-Dab1-NH2; (SEO ID No:276)
C[Hydantoin(C(O)-(GIu-D-Ala))-His-D-Phe-Arg-Trp-Dap]-NH2; (SEO ID No:276)
c[Hydantoin(C(O)-(GIu-His))-D-Phe-Arg-Trp-Dap]-NH2; (SEO lD No:277)
Hydantoin(C(O)-(Arg-GIy))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (SEO ID No:278)
Hydantoin C(O)- (Nle- Gly))- c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NHz; (SEO ID No:278)
Hydantoin C(O)- (Gly- Gly))- c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NHz; (SEO ID No:278)
Hydantoin (0)-(Nle-GIy))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NHZ; (SEO lD No:279)
Hydantoin C(O)- GIy-GIy))-C(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NHz: (SEO lD No:279)
Hydantoin C(O Nle-Gly )-C(Cys-D-AIa-His-D-Phe-Arg-Trp-Pen)-NH2; (SEO ID No:280)
Hydantoin C(O GIy-GIy))-C(Cys-D-AIa-His-D-Phe-Arg-Trp-Pen)-NH2; (SEO ID No:280)
Hydantoin C(O - AIa-GIy))-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-NHz; (SEO ID No:279)
Hydantoin C(O
Hydantoin C(O -
Hydantoin C 0
Aib-GIy))-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-NHz; (SEO ID No:279)
( - Val-Gly))-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-NH2; (SEO ID No:279)
Hydantoin C(O - Ile-GIy))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEO ID No:279)
Hydantoin C(O - Leu-GIy))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEO ID No:279)
Hydantoin C(O)- (Gly-Gly))- c(Cys- -Glu- His- D- 2- Nal- -A-rg Trp- Cys)- -NH2; (SEO ID NO: 281)
Hydantoin C(O)-(Nle-Gly) )-c(Cys-Glu-His-D-Z-NaI-Arg-Trp-Cys)-NHz; (SEO ID No:281)
(0)-(D-Arg-Gly))-c(Cys-GIu-His-D-Phe-Arg-Trp-Cys)-NHz; (SEO ID No:278)
Hydantoin C(O)- (D -Arg- Gly))- c(Cys-D-Ala- -His- D- Phe- -Arg- Trp- Cys)- NH2; (SEO ID NO: 279)
Hydantoin(
(D-Ala-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEO ID No:279)
Hydantoin
Gly- Arg)) c-(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2; (SEO lD No:285)
Gly-Arg))- c(Cys-Glu-His-D-2-NaI-Arg-Trp-Cys)-NHz; (SEO ID No:285)
ly-Arg))-C(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-NH2; (SEO ID No:286)
Hydantoin C(O
Hydantoin C(O
Hydantoin C(
C(O)- (Arg- Gly))- c(Cys- -D- Ala- His- D- Phe- -Arg- Trp- Cys)- NHg; (SEO ID NO: 279)
Hydantoin C(O)- (D -Arg-Gly))- c(Cys- D-Ala- His-D- 2- Nal- -A-rg -Trp-Cys)- NH2; (SEO ID NO: 282)
Hydantoin C(O )- (Arg- Gly))- c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NHz; (SEO ID No:282)
Hydantoin C(O)- (Ala- Nle))- c(Cys- -Glu- His- D- Phe- -A-rg Trp- Cys)- -NH2; (SEO ID NO: 283)
Hydantoin C(O)- (Val- Nle))- c(Cys- G-lu- His- D- Phe- --Arg Trp- Cys)- NHZ; (SEO ID NO: 283)
Hydantoin C(O)- (Gly- Nle))- c(Cys- G-l-u His- D- Phe- -Arg- Trp- Cys)- NH2; (SEO ID NO: 283)
Hydantoin C(O )- (Aöc- Nle))- c(Cys- D- Ala- His- D- --Phe-Arg Trp- Cys)- NHZ; (SEO ID NO: 284)
Hydantoin C(O)- (Gly-Nle))- c(Cys- D- Ala- His- D- Phe- -A-rg Trp- Cys)- NH2; (SEO lD NO: 284)
Hydantoin C(O)- (Ala- Nle))- c(Cys- -D-Ala- His- D- Phe- --Arg-Trp Cys)- -NH2; (SEO ID NO: 284)
Hydantoin C(O)- (D -Ala- -Nle))- c(Cys- D---Ala His- D- Phe- -A-rg-Trp Cys)- NH2; (SEO ID NO: 284)
Hydantoin C(O )- (Val- Nle))- c(Cys- D -A-Ia His- D- Phe- -A-rg-Trp Cys)- NH2; (SEO ID NO: 284)
Hydantoin C(O)- (Leu- Nle))- c(Cys- D- Ala- His- D- Phe- -A-rg Trp- Cys)- NH2; (SEO lD No:284)
Hydantoin C(O)- (Cha- Nle))- c(Cys- D- Ala- His- D- -P-he-Arg Trp- Cys)- NH2; (SEO ID NO: 284)
Hydantoin C(O)- (Aib- Nle))- c(Cys- D-Ala- His- D- Phe- Arg-Trp- Cys)- NH2; (SEO ID NO: 284)
Hydantoin(C(O
Hydantoin(C
)- ly-Arg))-C (Cys-D-AIa-His-D-2-NaI-Arg-Trp-Cys)-NH2; (SEO ID No:286)
Hydantoin C 0)-
(0 (Gly-D- Arg))- c(Cys-GIu-His-D-Phe-Arg-Trp-Cys)-NHz; (SEO ID NO:28?)
( (Gly-D- Arg))- c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NHz; (SEO ID No:288)
Hydantoin C(O ( )-
Hydantoin(C(O c(
c[Hydantoin(C
c[Hydantoin(C
c[Hydantoin(C
c[Hydantoin(C
c[Hydantoin(C
c[Hydantoin(C
c[Hydantoin(C
c[Hydantoin(C
c[Hydantoin(C
c[Hydantoin(C
Gly- -D- A-rg) C(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NHz; (SEO ID No:288)
-(Nle-AIa))-c Cys- G-Iu- His- D- Phe- --Arg Trp- Cys)- NH2; (SEO ID NO: 289)
O)-(AIa-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2, (SEO ID No:290)
O)- (Nle- Cys))- -D Ala- His-D- Phe- -Arg- Trp- Cys]- -NH2; (SEO ID NO: 290)
O)- (D- A-Ia- --Cys)) -D-Ala His- D- Phe- --Arg Trp- Cys]- -NH2; (SEO ID NO: 290)
0) (Aib-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (SEO ID No:290)
O)- (Val- Cys))- D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2; (SEO ID No:290)
0)- (Abu- Cys))- D-AIa-His-D-Phe-Arg-Trp-Cys]-NHz; (SEO lD No:290)
O)- (Leu- Cys))- D- Ala- His-D- Phe- --Arg-Trp Cys]- -;NH2 (SEO ID No:290)
0) (Ile-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NHz; (SEO ID No:290)
O)- (Cha- Cys))- D- Ala- His- D- Phe- -A-rg Trp- Cys]- -NH2; (SEO ID NO: 290)
O)- (Aöc-Cys))- D -A-la His- D- Phe- --Arg-Trp Cys]- NHz; (SEO ID NO: 290)
c[Hydantoin(C O)- (Phe- Cys))- D-AIa-His-D-Phe-Arg-Trp-Cys]-NH2; (SEO lD No:290)
c[Hydantoin(C O)- (GIy-Cys))-D-AIa-His-D-Phe-Arg-Trp-Cys]-NHz; (SEO ID No:290)
c[Hydantoin(C(O)-(GIy-Cys))-Glu-His-D-Phe-Arg-Trp-Cys]-NHz; (SEO ID No:291)
Ac-Tyr-Arg-C(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-NH2; (SEO lD No:292)
Ac-2-Nal-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NHz; (SEO ID No:292)
Ac-1-NaI-Arg-C(Cys-D-Ala-His-DPhe-Arg-Trp-Cys)-NH2; (SEO ID No:292)
Ac-Phe-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NHz; (SEO lD No:292)
Ac-Trp-Arg-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-NHz; (SEO ID No:292)
AC-Pff-Arg-C(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2; (SEO ID No:292)
H-His-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NHz; (SEO ID No:293) ve
Ac-His-Arg-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-NH2; (SEO lD No:292)
veya bunlarin farmasötik olarak kabul edilen tuzlarindan olusan gruptan seçilmistir.
8^^^6^^^8^^^
Bir uygulamada, ihtiyaci olan denegin insülin direncinin tedavisinde yararli olan melanokortin
reseptörü 4 agonisti, Ac-Arg-c(Cys-D-AIa-His-D-Phe-Arg-Trp-Cys)-NHz (SEO ID NO:50) veya
bunlarin farmasötik olarak kabul edilen tuzlaridir. Bir baska uygulamada, ihtiyaci olan
deneknin insülin direncinin tedavisinde yararli olan melanokortin reseptörü 4 agonisti,
Hydantoin(C(O)-(Arg-Gly))-c(Cys-GIu-His-D-Phe-Arg-Trp-Cys)-NHz (SEO ID NO: 278) veya
bunlarin farmasötik olarak kabul edilen tuzlaridir.
Burada tarif edilen bir baska uygulama, insülin direncinin tedavisinde yararli olan patent
hakki bildirimi bilesiginin veya bilesigi veya ilgili bilesigin farmasötik tuzunu içeren bilesimin
sürekli olarak, saatte bir, günde dört kez, günde üç kez, günde iki kez, günde bir kez, gün
asiri, haftada iki kez, haftada bir kez, iki haftada bir, ayda bir veya iki ayda bir veya daha
uzun araliklar ile verilmesidir.
Tedaviye ihtiyaci olan denek obez, fazla kilolu, normal kilolu veya zayif olabilir. Obez, fazla
kilolu, normal kilolu veya zayif denek tip II diyabet hastasi olabilir. Insülin direncinin
tedavisinde yararli olan patent hakki bildirimi bilesiginin veya bilesigi veya ilgili bilesigin
farmasötik tuzunu içeren bilesimin periferik yol ile verilmesi tercih edilen verme seklidir.
Periferik yol ile verme örnekleri, agizdan, deri altina zerk etme, periton içine, kas içine, damar
içine zerk etme, rektal, transdermal veya burun içine verme seklini içerir.
SEKILLERIN KISA AÇIKLAMASI:
Sekil 1: 100 nmoI/Kg seçilen bilesikler verildikten 6 saat sonra aç birakilan siçanlarin
besin tüketimi.
Sekil 2. Siçanlarda A Bilesiginin derialtina günde 75, 300 veya 600 nmoI/kg
verilmesinin (A) vücut agirligi, (B) kümülatif besin alimi, (C) insülin seviyeleri ve (D)
glikoz seviyeleri üzerindeki etkisi.
Sekil 3. Siçanlarda B Bilesiginin derialtina günde 75, 300 veya 600 nmoI/kg
verilmesinin (A) vücut agirligi, (B) kümülatif besin alimi, (C) insülin seviyeleri ve (D)
glikoz seviyeleri üzerindeki etkisi
verilmesinin kandaki glikoz seviyeleri üzerindeki etkisi.
Sekil 5. Obez farelerde A Bilesiginin periton içine 6.4 umoI/kg verilmesinin kandaki
glikoz seviyeleri üzerindeki etkisi.
BULUSUN DETAYLI AÇIKLAMASI
Yakin zamanda yapilan çalismalar, tüm dünyada asiri kilolu ve agir ve tedavisi pahali olan
çok çesitli saglik sorunlari olan insan sayisinin sasirtici derecede fazla oldugunu ortaya
koymaktadir. Dünya Saglik Örgütüne (WHO) göre, (Kouris-Blazos ve arkadaslarinin, Asya
asiri kiloludur ve bunlarin tahminen 300 milyonu obezdir. Sadece Avrupa Birliginde 5
yasindan küçük tahminen 22 milyon çocuk siddetli asiri kiloludur; asiri kilolu çocuklarin
sayisinin her yil 1.3 milyon artmasi beklenmektedir (Kosti ve arkadaslari, 2006, Cent. Eur. J.
Public Health, 14:151-159). Obezite, Metropolitan Life Insurance C0., tarafindan verilen
Istatistiksel Bültende (1959, 40:1) tanimlandigi üzere, kisinin normal vücut agirligindan % 20
- 25 fazla kilolu oldugu rahatsizliktir. Alternatif olarak, vücut kütle indeksi normalden % 25
fazla olan kisiler veya risk faktörleri ile normalden % 30 fazla olan kisiler obez olarak kabul
edilir (Bakiniz, Bray ve arkadaslari, Diabetes / Metabolism Review, 1988, 4:653-
sebeplerinden birisi yüksek kalorili beslenmedir (Riccardi ve arkadaslari, Clin. Nutr., 2004,
23:447-456).
Diyabet, çok sayida fazla kilolu ve obez kisinin yakalandigi kronik, sakat birakan bir
rahatsizliktir. Birlesik Devletlerde 20.8 milyon kisinin diyabet hastasi oldugu ve 8 milyonun
üzerinde ilave vakaya henüz teshis konulmamis oldugu tahmin edilmektedir (Cornell, Manag.
anilmaktadir), insülin direnci, bozulmus insülin sekresyonu ve hiperglisemi ile seyreden bir
hastaliktir. Tüm dünyada yaklasik 171 milyon kisinin tip II diyabet hastasi oldugu
düsünülmektedir; bu hastalik, çesitli mikrovasküler ve makrovasküler komplikasyonlar
yaratmakta ve morbiditeye veya mortaliteye yol açmaktadir (Mudaliar, Indian J. Med. Res.,
hastada glikozun kontrol altina alinmasinin zor olduguna da dikkat çekmektedir.
Azalmis insülin duyarliligi olarak da anilan insülin direnci, denegin kanindaki glikozu emmek
için gereken insülin miktarinin, normal insüline duyarli olmayan denegin kanindan ayni
miktarda glikozu emmek için gereken insülin miktari ile karsilastirildiginda arttigi
rahatsizliktir. Insülin direnci, obezite ile tip II diyabet arasindaki temel baglanti olarak kabul
bakiniz). Yüksek yagli diyet ile beslenen siçanlarda vücut agirliklarinin arttigi (diyete bagli
olarak gelisen obezite veya DIO) ve insülin direncinin düstügü bilinmektedir. Bu DIO siçanlar
obeziteye bagli insülin direnci mekanizmalari ile ilgili arastirmalar için hayvan modelini
DIO siçanlarda yag dokularinin boyutu ve agirligi artar ve beraberinde gelisen yag
hücrelerinin hipertrofisinin (asiri büyümesi) insülin duyarliligini düzenledigi bilinen leptin ve
adiponektin gibi adipositokinlerin salgilanmasinda degisiklige yol açtigi düsünülmektedir; yag
dokusundaki morfolojik degisikliklerin ve ayni zamanda adipositokinlerin plazma
seviyelerindeki degisikliklerin DIO siçanlarda insülin direncinin sebeplerinin arasinda oldugu
buradaki referanslarda özetlenmistir).
Melanokortinlerin enerji metabolizmasinda ve homeostazda büyük bir rol oynadigi ileri
sürülmektedir. POMC prekürsörden ayrilan melanokortinler beyindeki melanokortin reseptörü
ailesinin üyelerine baglanarak etki ederler. Melanokortinin beyindeki temel etkisi, besin
alimini azaltmaktir; ancak, dogrudan serebral ventriküle enjekte edilen melanokortin
agonistlerin veya antagonistlerin besinler çekilirken veya besin alimi sabit tutuldugunda
periferideki insülin hareketlerine etki ettigi de görülmüstür (bkz. Schwartz ve arkadaslari,
Birlikte ele alindiginda bu veriler, melanokortinlerin merkezi olarak verilmesinin insülin
duyarliligini etkiledigini ve bunun enerji dengesinden bagimsiz olabilecegini ortaya
siçanlarina melanokortin agonistinin intraserebral enjeksiyonlarinin periferide insülin
duyarliligini iyilestirdigini, beyaz yag dokusundaki yag depolayan hücrelerin boyutunu ve
artan sayisini azalttigini ve karacigerde trigliserid birikimini azalttigini kanitlamistir.
Tedavi edilmeye ihtiyaç duyan çok sayida asiri kilolu ve / veya insülin direnci olan denek
dikkate alindiginda, intraserebral yol ile vermek, ilaci hastalarda yaymanin pek mümkün
olmayan bir yoludur. Dolayisi ile teknolojide, insülin duyarliligi, beyaz yag dokusunun
hücresel özellikleri, trigliserid seviyeleri ve benzeri insülin hareketi parametrelerine ve enerji
metabolizmasina etki etmek üzere periferik yol ile vermeye uygun olan melanokortin
agonistlerini ve antagonistlerini belirleme ihtiyaci söz konusudur.
Terminoloji ve Kisaltmalar
Burada kullanildigi sekli ile, “obez denek" veya memeli, normal vücut agirligindan yaklasik %
veya daha fazla vücut agirligina sahip olan denek olarak nitelendirilir. Normal vücut
agirligi, denegin insülin metabolizmasinin normal oldugu zaman gibi zaman içinde daha
önceki bir noktadaki vücut agirligi ile karsilastirilarak veya denegin kilosunun benzer yasta
ve/ veya durumda olan diger deneklerin ortalama agirliklari ile karsilastirilarak belirlenebilir.
Burada kullanildigi sekli ile, ”fazla kilolu denek” veya memeli, normal vücut agirligindan
yaklasik % 5 ila yaklasik % 20 arasinda daha fazla vücut agirligina sahip olan denek olarak
nitelendirilir. Normal vücut agirligi, denegin insülin metabolizmasinin normal oldugu zaman
gibi zaman içinde daha önceki bir noktadaki vücut agirligi ile karsilastirilarak veya denegin
kilosunun benzer yasta ve / veya durumda olan diger deneklerin ortalama agirliklari ile
karsilastirilarak belirlenebilir.
Burada kullanildigi sekli ile, “normal denek” veya memeli, normal vücut agirliginin yaklasik %
fazlasi ila yaklasik % 5 daha azi arasinda vücut agirligina sahip olan denek olarak
nitelendirilir. Normal vücut agirligi, denegin insülin metabolizmasinin normal oldugu zaman
gibi zaman içinde daha önceki bir noktadaki vücut agirligi ile karsilastirilarak veya denegin
kilosunun benzer yasta ve / veya durumda olan diger deneklerin ortalama agirliklari ile
karsilastirilarak belirlenebilir.
Burada kullanildigi sekli ile, “zayif denek” veya memeli, normal vücut agirligindan yaklasik %
ila % 30 veyahutta % 50 daha az vücut agirligina sahip olan denek olarak nitelendirilir.
Normal vücut agirligi, denegin insülin metabolizmasinin normal oldugu zaman gibi zaman
içinde daha önceki bir noktadaki vücut agirligi ile karsilastirilarak veya denegin kilosunun
benzer yasta ve / veya durumda olan diger deneklerin ortalama agirliklari ile karsilastirilarak
belirlenebilir.
Burada kullanildigi sekli ile, "tedavi", "tedavi etme" ve “tedavi etmek” terimleri, palyatif, küratif
ve profilaktik tedaviyi içerir.
Burada kullanildigi sekli ile, “ölçülebilir”, biyolojik etkinin hem çogaltilabilir oldugunu hem de
analizin bazal degiskenliginden önemli ölçüde farkli oldugunu ifade eder.
Burada kullanilan sekli ile, periferik yol ile verme, mevcut patent hakki bildirimin bilesiginin
veya bilesigi ihtiva eden bilesimin, intrakraniyal yol ile vermek hariç olmak üzere tüm verilis
sekillerini içerir. Periferik yol ile verme örnekleri, agizdan, parenteral (örnegin, kas içine,
periton içine, damar içine veya deri altina enjeksiyon, implant ve benzeri), nazal, vajinal,
rektal, dil alti veya transdermal flaster uygulamalari ve benzerlerini içeren topikal ilaç verme
yollarini içerir, ancak bunlar ile sinirli degildir.
Burada ve basvurunun tamaminda kullanilan sekli ile “denek", örnegin insan, siçan, fare
veya çiftlik hayvani gibi ancak bunlar ile sinirli olmayan memeli veya memeli olmayan bir
hayvani ifade eder. Denege atifta bulunmak, mutlaka bir hastaligin veya rahatsizligin
varligini belirttigi anlamina gelmez. “Denek” terimi, örnegin deneyin bir parçasi olarak belli
ölçüde melanokortin analog verilen memeli veya memeli olmayan hayvani, hastaligi veya
rahatsizligi iyilestirmek için tedavi edilen memeli veya memeli olmayan hayvani ve hastaligin
veya rahatsizligin baslamasini önlemek veya geciktirmek için profilaktik olarak tedavi edilen
memeli veya memeli olmayan hayvani içerir. Söz konusu memeliler, örnegin bebek, çocuk,
yetiskin veya yasli yetiskin gibi herhangi bir yastaki insan denekler olabilir.
Patent hakki bildiriminin bilesiginin veya bilesiminin “terapötik olarak kabul edilebilir miktari”,
formülden veya verilme yolundan bagimsiz olarak denekte istenilen biyolojik tepkiyi gösteren
miktardir. Terapötik miktarin biyolojik etkisi organizmada birçok seviyede ortaya çikabilir ve
pek çok seviyede ölçülebilir. Örnegin, terapötik miktarin biyolojik etkisi hücresel seviyede
ortaya çikabilir ve melanokortine ve / veya melanokortin analoga baglanan reseptörde
tepkinin ölçülmesi ile hücresel seviyede ölçülebilir veya terapötik miktarin biyolojik etkisi
insülin seviyelerindeki artisi / düsüsü etkilemesi gibi sistem seviyesinde meydana gelebilir ve
sistem seviyesinde ölçülebilir. Terapötik miktarin biyolojik etkisi, denekte hastaligin veya
rahatsizligin semptomunun (semptomlarinin) veya ilerlemesinin hafifletilmesi gibi organizma
seviyesinde meydana gelebilir ve ölçülebilir. Patent hakki bildiriminin bilesiginin veya
bilesiminin terapötik olarak kabul edilebilir miktari, formülden veya verilme yolundan
bagimsiz olarak denekte bir veya birden fazla biyolojik tepkiye yol açabilir. Patent hakki
bildiriminin bilesiginin veya bilesiminin laboratuvar ortaminda (in vitro) bir sistemde teste tabi
tutulmasi durumunda, bilesigin veya bilesimin terapötik olarak kabul edilebilir miktari, seçilen
in vitro sistemde verilen ölçülebilir tepki olarak görülebilir.
Peptidleri tanimlamak için kullanilan terimler, teknikte tipik olarak kullanilan ve N-
terminalindeki amino grubun solda ve C-terminalindeki karboksil grubun sagda gösterildigi
terimlerdir. D ve L izomerik formlara sahip olan amino asitlerde, aksi açik bir sekilde
belirtilmedikçe, amino asidin L formu gösterilir.
Insülin direncinin, kilo kaybederek veya kilo kaybi olmaksizin tedavisinde yararli olan patent
hakki bildiriminin bilesiklerinin bir veya birden fazla kiral merkezleri olabilir ve bu merkezler
birkaç farkli stereo izomerik formda bulunur. Bütün stereo izomerler ve karisimlari mevcut
bildirimin kapsamina dahil edilmistir. Rasemik bilesikler ya preparatif HPLC ve bir kolon ve
kiral durgun faz kullanilarak ayrilir ya da teknikte uzman kisiler tarafindan bilinen
yöntemlerden yararlanilarak münferit enantiyomerleri verecek sekilde ayristirilabilir. Buna
ilaveten, kiral ara bilesikler ayristirilabilir ve patent hakki bildiriminin kiral bilesiklerini
hazirlamak için kullanilabilir.
Patent hakki bildiriminin insülin direncinin, kilo kaybederek veya kilo kaybi olmaksizin
tedavisinde yararli olan bilesikleri, bir veya birden fazla totomerik formda bulunabilir. Bütün
totomerler ve bunlarin karisimlari, mevcut patent hakki bildiriminin kapsamina dahil
de kapsayacaktir.
Aksi belirtilmedigi sürece, burada kullanilan bütün teknik ve bilimsel terimler, bu bulusun ait
oldugu teknikte uzman bir kisi tarafindan genel olarak anlasilan ile ayni anlama sahiptir.
Sembol Anlami
Abu oi-aminobütrik asit
Ac asil grup
Acc 1-amino-1-siklo(Cg-Cg)alkil karboksilik asit
A3c 1-amino-1-siklopropankarboksilik asit
A4c 1-amino-1-siklobutankarboksilik asit
A5C 1-amino-1-siklopentankarboksilik asit
Aöc 1-amino-1-siklohekzankarboksilik asit
Aha 7-aminoheptan0ik asit
Ahx ö-aminohekzanoik asit
Aib oi-aminoizobütrik asit
Aic 2-aminoindan-2-karboksilik asit
Ala veya A alanin
ß-Ala ß-alanin
Apc Yapiyi gösterir:
Sembol
Arg veya R
Asn veya N
Asp veya D
4-Br-Phe
Cys veya C
2-Fua
Gln veya Q
Glu veya E
Gly veya G
His veya H
3-Hyp
Anlami
-amin0pentanoik asit (HN-(CH2)4-C(O)
homoarginin
asparajin
Aspartik asit
3-benzotienilalanin
4,4'-bifenilalanin, yapiyla gösterilen
4-benzoilfenilalanin
4-bromo-fenilalanin
ß-siklohekzilalanin
homo-siklohekzilalanin
siklohekzilglisin
homosistein
2,4-diamin0bütrik asit
2,3-diamin0propiy0nik asit
ßß-difenilalanin
Asagidaki yapida 8-amino-3,6-dioksaoktanoik
/Ewo/VOÄ
ß-(2-furiI)-alanin
4-amin0bütrik asit
glutamin
glutamik asit
histidin
trans-S-hidroksi-L-prolin, diger bir deyisle, (28,
38)-3-hidr0ksipirrolidin-2-karboksilik asit
Sembol
4-Hyp
Leu veya L
Lys veya K
Met veya M
1-Nal
2-Nal
2-Pal
3-Pal
4-Pal
Phe veya F
Pro veya P
Ser veya 8
2-Thi
3-Thi
Thr veya T
Trp veya W
Tyr veya Y
D-(Et)Tyr
Val veya V
Anlami
4-hidr0ksipr0lin, diger bir deyisle, (28, 4R)-4-
hidroksipirrolidin-2-karboksilik asit
izolösin
homolösin
metionin
ß-homometionin
ß-(1-naftil)alanin:
ß-(2-naftil)alanin
Nipekotik asit
norlösin
oktahidroindoI-2-karboksilik asit
ß-(2-piridil)alanin
ß-(3-piridil)alanin
ß-(4-piridil)alanin
penisilamin
(S)-pentaflorofenilalanin
fenilalanin
homofenilalanin
prolin
homoprolin
tert-Lösin
ß-(4-tiyazolil)alanin
ß-(2-tiyenil)alanin
ß-(3-tiyenil)alanin
treonin
triptofan
tirosin
Asagidaki yapidadir
Burada kullanilan belirli diger kisaltmalar, asagida gösterilen sekilde tanimlanmistir:
Aksi belirtilmedigi sürece,
tert-butiloksikarbonil
Benzil
dikhlorometan
N, N-diizopropilkarbodiimid
diizopropiletil amin
4-{N-(1-(4,4-dimetiI-2,6-dioksosikloheksiliden)-3-
metilbütiI)-amin0}benzil
4-(dimetilamin0)piridin
dimetilformamid
2,4-dinitr0fenil
Florenilmetil
floreniImetiloksikarbonil
Formil
2-(1H-benzotriazoI-1-yI)-1,1,3,3-tetrametiluronyum
hekzaflorofosfat
Sikloheksil
O-(7-azabenzotriazoI-1-yl)-1,1,3,3-tetrametiluronyum
hekzaflorofosfat
1-hidr0ksi-benzotriazol
4-metilbenzhidrilamin
4-met0ksitritil
N-metilpirrolidon
oksi-tert-bütil
2,2,4,6,7-pentametildihidrobenzofuran-S-sulfonil
bromo-tris-pirrolidin-fosfonyum hekzaflorofosfat
tert-bütil
triizopropilsilan
triroro asetik asit
tetrametilfloroforamidinyum hekzaflorofosfat
Benziloksikarbonil
bu patent hakki bildiriminde N-terminal amino asit disindaki bütün
amino asit kisaltmalari (örnegin, Ala) -NH-C(R)(R')-CO- yapisini simgeler, burada R ve R'
bagimsiz olarak hidrojen veya amino asit yan zinciridir (örnegin, Ala için R = CH3 ve R' = H)
veya R ve R' halka sistemi olusturmak için birlestirilebilir.
N-terminal amino asit için, kisaltma asagidaki yapiyi simgeler:
No:7), peptidin C-terminalinin amidlendigini gösterir. Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-
Cys) (SEQ ID NO:36), veya alternatif olarak Ac-NIe-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-
OH (SEO ID NO:36), C- terminalinin serbest asit oldugunu gösterir.
"-c(Cys-Cys)-" veya "-cyclo(Cys-Cys)-" asagidaki yapiyi gösterir:
HO HO
Basvuru sahipleri belirli durumlari ve / veya türleri adlandirmak için kullanilan asagidaki
kisaltmalari tasarlamistir:
burada, "Aa" amino asit asagida gösterilen yapidadir:
ve "Ab" amino asit asagidaki yapidadir:
örnegin, "c[Hidantoin(C(O)-(Cys-Ab))-A1-AZ-AS-A4-Cys]-" olarak ifade edilen bilesik asagida
belirtilen yapidadir:
N A1-A2-A3-A4-N
buna karsilik "c[Hidantoin(C(O)-(Ab-Cys))-A1-A2-A3-A4-Cys]-" olarak ifade edilen bilesik
asagidaki yapidadir:
Daha fazla yönlendirme için, "c[Hidantoin(C(O)-(Asp-Ab))-A1-A2-A3-A4-Lys]-“ asagidaki
bilesigi ifade eder:
buna karsilik "c[Hidantoin(C(O)-(Dap-Ab))-A1-A2-A3-A4-Asp]-" formülü asagida belirtildigi
HNWNKLLA1-A2-A3-A4_N
i'Asil", R"-C(O)- 'yu ifade eder; burada R", H, alkil, ikameli alkil, heteroalkil, ikameli heteroalkil,
alkenil, ikameli alkenil, aril, alkilaril veya ikameli alkilarildir ve belirli bir genel formülde “Ac”
olarak gösterilir.
bag ile birlesen hidrokarbon grubunu ifade eder. Alkil hidrokarbon grubu düz zincirli olabilir
veya bir veya birden fazla dal veya siklik grup içerebilir.
veya birden fazla hidroksimetil, hidroksietil, hidroksipropil, hidroksibütil, hidroksipentil,
hidroksihekzil ve benzeri gibi hidroksi radikalin yerlestirildigi alkil grubunu ifade eder.
(bir diger deyis ile, flor, klor, brom ve iyot) -OH, -CN, -SH, -NH2, -NHCH3, -N02, ve -C1_20 alkil
ihtiva eden ve burada söz konusu -Cim alkilin opsiyonel olarak yerine her vaka için bagimsiz
olarak halojenler, -CF3, -OCH3, 'OCFg, ve -(CH2)0-20-COOH içeren gruptan seçilen bir veya
birden fazla baska atomun yerlestirildigi gruptan seçilen bir veya birden fazla atomun yerine
geçen baska atomlarin yerlestirildigi alkili ifade eder. Farkli durumlarda, 1, 2, 3 veya 4 ornatik
(yer degisimli) bulunur. -(CH2)O_2o-COOH ,un bulunmasi alkil asidin üretilmesine yol açar. -
(CH0-20-COOH 'dan olusan alkil asitler ile ilgili sinirlayici
olmayan örnekler 2-norbornan asetik asit, tert-bütrik asit, 3-siklopentil propiyonik asit ve
benzerlerini içerir.
asagidaki gruplardan bir veya birden fazlasinin yerlestirildigi alkili ifade eder: amino, amido, -
0-, -8- veya karbonil. Farkli durumlarda 1 veya 2 heteroatom bulunmaktadir.
halojen (bir diger deyis ile, flor, klor, brom ve iyot) -OH, -CN, -SH, -NH2, -NHCH3, -N02, ve -
C1-20 alkil ihtiva eden ve burada söz konusu -C1_20 alkilin opsiyonel olarak yerine her vaka için
bagimsiz olarak halojenler, -CF3, -OCH3, -OCF3, ve -(CH2)0.20-COOH içeren gruptan seçilen
bir veya birden fazla baska atomun yerlestirildigi gruptan seçilen bir veya birden fazla atomun
yerine geçen baska atomlarin yerlestirildigi heteroalkili ifade eder. Farkli durumlarda, 1, 2, 3
veya 4 ornatik bulunur.
sayida karbondan olusan hidrokarbon grubunu ifade eder. Alkenil hidrokarbon grubu düz
zincirli olabilir veya bir veya birden fazla dal veya siklik grup içerebilir.
diger deyis ile, flor, klor, brom ve iyot) -OH, -CN, -SH, -NH2, 'NHCHg, -N02, ve -C1.20 alkil
ihtiva eden ve burada söz konusu -C1.20 alkilin opsiyonel olarak yerine her vaka için bagimsiz
olarak halojenler, -CFS, 'OCHg, -OCF3, ve -(CH2)Ü_20-COOH içeren gruptan seçilen bir veya
birden fazla baska atomun yerlestirildigi gruptan seçilen bir veya birden fazla atomun yerine
geçen baska atomlarin yerlestirildigi alkenili ifade eder. Farkli durumlarda, 1, 2, 3 veya 4
ornatik bulunur.
konjüge veya kaynastirilmis halka sisteminden olusan opsiyonel olarak bilesimde bulunan
atomlarin yerine baska atomlarin yerlestirildigi aromatik grubu ifade eder. Aril, karboksilik aril,
heterosiklik aril ve biaril gruplarini içerir. Tercihli bir sekilde aril, 5 veya 6 elemanli halkadir.
Heterosiklik aril için tercih edilen atomlar, bir veya birden fazla sülfür, oksijen ve / veya
nitrojendir. Arille ilgili sinirlayici Olmayan örnekler, fenil, 1-naftil, 2-naftil, indol, kinolin, 2-
imidazol, 9-antrasen ve benzerlerini içerir. Aril bilesiklerinde atomlarin yerini baska atomlarin
aldigi bilesikler, -C1.20 alkil, -C1_20 alkoksi, halojen (bir diger deyisle, flor, klor, brom ve iyot),
bilesikteki atomlarin yerini halojen atomlarinin aldigi -OH, -CN, -SH, -NH2, 'N02, -Cmo alkil, -
4 ornatik içerir.
C2-C12 bulunur.
Herhangi bir tereddüde mahal vermemek için, aksi belirtilmedikçe, ikameli terimi bilesikteki
atomlarin yerine tanimlanan gruplarindan bir veya birden fazlasinin geçtigini ifade eder.
Gruplarin bir takim alternatif gruplardan seçildigi durumlarda, seçilen gruplar ayni veya farkli
olabilir. Herhangi bir tereddüde mahal vermemek için, “bagimsiz olarak” terimi birden fazla
ortanigin olasi birkaç ortanik arasindan seçildigi durumda, söz konusu ornatiklarin ayni veya
farkli olabilecegini ifade eder.
Patent hakki bildiriminin bilesiginin bazik merkez ihtiva eden farmasötik olarak kabul edilen
tuzlari, örnegin hidroklorik, hidrobromik, hidroiyodik, sülfürik ve fosforik asit gibi inorganik
asitler, karboksilik asitler veya organo-sülfonik asitlerle olusan toksik olmayan ilave tuzlardir.
Örnekler, HCI, HBr, HI, sülfat veya bisülfat, nitrat, fosfat veya hidrojen fosfat asetat, benzoat,
süksinat, sakkarat, fumarat, maleat, Iaktat, sitrat, tartarat, glukonat, kamsilat, metansülfonat,
etansülfonat, benzensülfonat, p-toluensülfonat ve pamoat tuzlarini içerir. Patent hakki
bildiriminin bilesikleri ayni zamanda farmasötik olarak kabul edilen metal tuzlari, özellik ile de
bazlar ile birlikte toksik olmayan alkali ve toprak alkali metal tuzlari da saglar. Örnekler,
sodyum, potasyum, alüminyum, kalsiyum, magnezyum, çinko ve dietanolamin tuzlarini içerir
(Berge, S. M. ve arkadaslari, J. Pharm. Sci., 66:1-19 (1977); Gould, P.L., Int'l J.
Patent hakki bildiriminin bilesiginin farmasötik olarak kabul edilen solvatlari, bunlarin
hidratlarini da içerir. Ayrica patent hakki bildiriminin ve patent hakki bildiriminin çesitli
tuzlarinin kapsami bunlarin polimoflarini da Içermektedir. Bundan sonra, bilesikler,
bilesiklerin farmasötik olarak kabul edilen tuzlari, solvatlari veya patent hakki bildiriminin
herhangi bir yönünde / alaninda tanimlanan polimorflari (kimyasal proseslerdeki ara bilesikler
disinda) "patent hakki bildiriminin bilesikleri” olarak anilacaktir.
Laboratuvar (In vitro) çalismalari
Mevcut patent hakki bildiriminin bilesiklerinin asagidaki prosedürlere uygun olarak, bir veya
birden fazla melanokortin reseptörü ligandi olarak aktivitesi test edilebilir ve edilmistir.
Teknikte uzman bir kisi patent hakki bildiriminin bilesiklerinin melanokortin reseptörü
moleküllerine baglanma aktivitelerini tahlil etmek için burada tarif edilenlere benzer
prosedürlerin kullanilabilecegini bilecektir.
Radyoligand Baglanma Deneyleri
Laboratuvarda (in vitro) reseptör baglanma deneylerinde kullanilan hücre zarlari, sabit olarak
hMC-R reseptörünün 1, 3, 4 veya 5 alt türlerini ifade eden transjenik CHO-K1 hücrelerinden
elde edilmistir. Istenilen hMC-R reseptörü türünü ifade eden CHO-K1 hücreleri buz
soguklugunda pH 7.4 degerde 50 mM Tris-HCI içinde ultrasonik banyoda tutulmus
süspansiyona alinmis ve 10 dakika süre ile yaklasik 4°C 'de 50,000 9 'da santrifüje tabi
tutulmustur. Hücre zarlarini ihtiva eden yikanmis peletler yaklasik - 80°C 'de muhafaza
edilmistir.
baglanmanin yarismali inhibisyonu polipropilen 96 kuyulu plaklarda yürütülmüstür. Yukarida
tarif edildigi gibi hazirlanan hücre zarlari (1 - 10 pg protein/kuyu) ph 7.4 degerde, % 2 bovin
serum albümini (BSA), 5 mM MgCIg, 1 mM CaCIz ve 0.1 mg/mL basitrasin içeren 50 mM Tris-
HCI içinde, artan yogunlukta test bilesimi ile ve 0.1-0.3 nM [125l]-NDP-a-MSH ile yaklasik 90 -
120 dakika süre ile yaklasik 37°C sicaklikta inkübe edilmistir. [125I1-NDP-a-MSH”ye bagli
(w/v) polietilenimin (PEI) içinde ön yikama yapilarak, fiberglas filtre plakalarindan (Unifilter®;
Packard) filtre edilerek ayrilmistir. Filtreler üç kez pH 7.4 degerde yaklasik 0 - 4°C sicaklikta
50 mM Tris-HCI ile yikanmis ve ardindan Packard Topcount® sintilasyon sayaci kullanilarak
radyoaktivite deneyi yapilmistir. Baglama verileri bilgisayar destekli dogrusal olmayan
regresyon analizi ile (XL fit; IDBS) analiz edilmistir. Seçilen bilesikler yukarida ele alinan
deney kullanilarak test edilmis ve baglanma sabitleri (nMde Ki) Tablo 5, 6, 7 ve 8 'de rapor
edilmistir.
TABLO 5 - Seçilen Bilesikler için Radyoligand Baglanma Deneyi Verileri
Bile ik Ki hMC1- KI hMC3- KihMC4-R Ki hMC5- Ki hMC1- SEO ID
S R R R R/MC4-R NO:
Ac-Arg-c(Cys-D-Ala-His-D- SEQ ID
Ac-D-Arg-C(Cys-D-Aia-His- SEQ ID
Ac-D-Arg-c(Cys-D-Ala-His- SEQ iD
AC-D-Arg-C(Cys-His-D-Phe- SEQ ID
Ac-AIg-C(Cys-D-Ala-His-D- SEQ ID
Ac-D-Arg-c(Asp-HIs-D- SEQ ID
Bile ik Ki KI Ki Ki Ki hMC1-R SEQ ID
s hMC1- R hMC3-R hMC4-R hMC5- R /lVIC4-R NO:
AC-NIe-C(Cys-D-A1a-His-D- SEQ ID
Ac-NIe-c(Cys-D-Ala-l-lis-D- SEQ [D
D-Phe-C(Cys-His-D-(Et)Tyr- SE Q ID
Nle-C(Cys-His-D-Phe-Arg- SEQ lD
AC*N]E*C(C)›'S*HISIDIP1'IEI SEQ ID
Nle-C(Cys-His-D-Phe-Arg- SEQ ID
Bile ik Ki KI KI KI KI hMC1-R SEQ ID
D-Phe-c(Cys-His-D-Phe- SE ID
DýPheýc(CysýHisýDýPheý
Ac-hCha-c(Asp-His-D-Phe- SEQ ID
Ac-D-Chg-c(Asp-His~D- SE ID
Ac-hPhe-c(Asp-His-D-Phe- SEQ iD
Ac-Nle-c(Pen-D-Ala-His-D- SEQ lD
Ac-Nle-c(Cys-D-Ala-His-D- SEQ ID
Thr-NHz `
D-Phe-c(Cys-His-D-(Et)Tyr- SE Q ID
Thr-N Hz
D-Phe-C(Cys-His-D-Phe-
hArg-Bip-ß-AIa-D-CyS)-
Thr-N Hz
Bilesik
D-Phe-c(Cys-His-D-(Et)Tyr-
hArg-Bip-ß-AIa-D-Cys)-
Ac-Nle-C(Cys-D-Ala-His-D-
Phe-Arg-Trp-Cly-Cys)-NHz
Ac-N]e-C(Cys-D-A1a-His-D-
Phe-Arg-Trp-D-AIa-Cys)-
Ac-N]e-c(Cys-D-A]a-Hîs-D-
Phe-Arg-Trp-ß-Ala-Cys)-
Ac-N]e-C(Cys-D-A1a-His-D-
Phe-Arg-Trp-Gaba-Cys)-
Ac-N]e-c(Cys-D-A1a-His-D-
Phe-Arg-Trp-Apn-Cys)-
Ac-NIe-c(Asp-D-AIa-His-D-
Phe-Arg-Trp-Lys)-NH;›
Ac-Nle-c(Asp-D-Ala-His-D-
Phe-Arg-Ba]-Lys)-NH2
Ac-c(Cys-Glu-His-D-Phe-
Arg-Trp-Ala-Cys)-N1-lz
AC-C(Cys-Glu-His-D-Phe-
Arg-Z-Na]-A1a-Cys)-NH2
Ac-c(Cys-D-Ala-His-D-Phe-
Arg-Trp-Ala-Cys)-NI-12
Ac-c(Cys-D-A1a-His-D-Phe-
Arg-Z-Na]-AIa-Cys)-NH2
Ac-Nle-C(Cys-D-Äla-His-D-
Phe-Arg-Trp-Ala-Cys)-NH:
Ac-Nle-C(Cys-D-Ala-His-D-
Phe-Arg-Trp-Gaba-Cys)-
Ac-N Je-C(Cys-D-Ala-His-D-
Phe-Arg-Trp-Pen)-OH
Ac-N]e-c(Cys-D-Abu-His-
D-Phe-Arg-Trp-Cys)-NI-Ii
Ac-N]e-c(Cys-D-VaI-His-D-
Phe-Arg-Trp-Cys)-NI-Iz
AC-Nle-C(Cys-D-IIe-His-D-
Phe-A rg-Trp-Cys)-N Hz
AC-Nle-c(Cys-D-Leu-His-D-
Phe-Arg-Trp-CyS)-NH2
0.128
0.352
0.995
0.848
0.659
0.536
> 10000
KI hMC1-R SEQ ID
Bilesik Ki Ki KI Ki KihMC1-R SEQID
Arg-Trp-Gaba-Cvs)-Nl-Ii NO:39
Bilesik
Ac-Nle-C(Cys-His-D-Z-Nal-
Arg-Trp-AhX-Cys)-NHz
Ac-hPhe-c(Asp-His-D-2-
NaJ-Arg-Trp-Gaba-Lys)-
Ac-Cha-c(Asp-His-D-2-N al-
Arz-TrD-Caba-Lvs)-NH2
Bilesik
Ac-Arg-C(Cys-D-Ala-His-D-
2-Na l -Arg-Trp-Cys)-N Hz
KI KI KI KI KI hMC1-R SEQ ID
Tablo 5C
Ki Ki Ki Ki Ki MC1-R SEQ lD
TABLO 6 - Seçilen Bilesikler için Radyoligand Baglanma Deneyi Verileri
Bilesik
Ac-c(Cys-Glu-l-lis-D-Z-Nal-Arg-Trp-Ala-
Cys)-Pro-Pro-Lys-Asp-NI-b (SEQ ID No:269)
Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-
Arg-Nle-C(Asp-His-D-2-Nal-Arg-Trp-Lys)-
NI-Iz (SEQ ID NO:60)
Tyr-Cly-Arg-Lys-Lys-Arg-Arg-Cln-Arg-Arg-
Arg-Doc-Nle-c(Asp-His-D-Z-Nal-Arg-Trp-
Lys)-NH2 (SEQ ID NO:61)
N le-C(Asp-His-D-Z-NaI-Arg-Trp-Lys)-_{S-Ala-
TyrýGIyýArg*LysýLysýArgýArgýGlnýArgýArg*
ArgýNHi (SEQ ID NO:62)
Ac-Nle-C(Asp-l-lis-D-2-N al-Arg-Trp-Lys)-ß-
Ala-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-
Arg-Arg-NI-Iz (SEQ ID NO:62)
H-NIe-C(Asp-His-D-Z-Nal-Arg-Trp-Lys)-DOC-
DOCITyrýGîy*ArgýLysýLySýArgýArgýGînýArg*
Arg-Arg-NH: (SEQ 1D NO:63)
Ac-Nle-c(Asp-His-D-Z-Na]-Arg-Trp-Lys)-
Pro-Pro-Lys-Asp-Tyr-Cly-Arg-Lys-LyS-Ai'g-
Arsz-CIn-Arg-Arg-Arsz-NH: (SEQ ID NO:64)
Ac-C(Cys-Glu-His-D-Z-Nal-Arg-Trp-Gly-
Cys)-Pr0-Pro-Lys-Asp-Tyr-Cly-Arg-Lys-Lys-
Arg-Arg-Cln-Arg-Arg-Arg-NHz (SEQ 1D
Ac-Nle-c(Asp-His-D-2-Na1-Arg-Trp-Lys)-ß-
Ala-_ß-Ala-Tyr-Gly-Arg-Lys-Lys-Arg-Arb-
Ghi-Arg-Arg-Arg-NI-Iz (SEQ ID NO:66)
Tablo 6A
Bilesik
Ac-Nle-c(Asp-His-D-Z-Nal-Arg-Trp-Lys)-
Pro-Pro-Lys-Asp-Doc-Tyr-GIy-Arg-Lys-Lys-
Arg-Arg-Glri-Arg-Arg-Arg-NHz (SEQ ID
Ac-C(Cys-C1u-His-D-Z-Nal-Arg-Trp-Gly-
C ys)- Pro-Pro-Lys-Asp-DoC-Tyr-Gl y-Arg-Lys-
Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH: (SEQ ID
AC-C(Cys-GILi-His-D-Z-Nal-Arg-Trp-Ala-
Cy5)-Pr0-Pro-Lys-Asp-ß-Ala-Tyr-Gly-A rg-
Lys-Lys-Arg-Arg-Cln-Arg-Arg-Arg-NI-Iz
(SEQ ID NO:71)
AC-C(CyS-CIu-His-D-Z-NaI-Arg-Trp-Ala-
Cys)-Pi'0-Pro-Lys-ASp-DOC-Tyr-Gly-Arg-Lys-
Lys-Arg-Arg-Gln-Arg-Arg-Arg-NI-Iz (SEQ ID
Ac-C(Cys-Glu-HiS-D-2-Nal-Arg-Z-Nal-Ala-
Cys)-Pr0-Pr0-Lys-Asp-NH2 (SEQ ID No:269)
Ac-C(Cys-G1 u -H i s-D-Z-Nal-Arg-l -NaI-AI a-
Cys)-Pr0-Pr0-Lys-ASp-NH2 (SEQ ID No:269)
Ac-c(Cys-Glu-His-D-Z-Nal-Arg-Bal-Ala-Cys)-
Pro-Pro-Lys-Asp-NHz (SEQ ID No:269)
Ac-Nle-c(Asp-H is-D-Z-Na I-Arg-Trp-Lys)-
Doc-Doc-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-
Arg-Arg-Arg-NI-Iz (SEQ ID No:701)
AC-C(Cys-C1u-His-D-2-Na]-Arg-2-Nal-Ala-
Cy5)-Pro-Pro-Lys-Asp-ß-Ala-Tyr-Cly-Arg-
Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NI-h
(SEQ ID NO:71)
Ac-c(Cys-Glu-His-D-Z-Nal-Arg-Bal-Ala-Cys)-
Pro-Pro-Lys-Asp-ß-A]a-Arg-Arg-Arg-Arg-
Arg-GIn-Arg-Arg-Arg-N Hz (SEQ ID NO:83)
Ac-c(Cys-G1u-His-D-Z-Na1-Arg-Bal-A1a-Cys)-
Pro-Pro-Lys-Asp-_ß-Ala-Gly-Arg-Arg-Arg-
Arg-Arg-Cln-Arg-Arg-Arg-NI-Iz (SEQ ID
Ac-c(Cys-Glu-I-Iis-D-Z-Nal-Arg-Bal-Ala-Cys)-
Pro-Pro-Lys-Asp-jS-Ala-Tyr-Gly-Arg-Arg-
Arg-Arg-Arg-Gln-Arg-Arg-Arg-NHz (SEQ ID
Ac-C(Cys-CIu-His-D-Z-Nal-Arg-Trp-Ala-
C ys)-Pr0-Pr0-Lys-Asp-ßAla-Tyr-Gly-Arsj-
Lys-Lys-Arg-GI n-Arg-Arg-Arg-Arg-N Hz
(SEQ ID NO:75)
AC-c(Cys-Glu-Hls-D-2-Na1-Arg-Trp-Ala-
Cys)-Pr0-Pr0-Lys-Asp-ß-Ala-Tyr-Cly-Arg-
Lys-Lys-Gln-Arg-Arg-Arg-Arg-Arg-NH:
(SEQ 1D NO:76)
KI hMC1-R
0.144
0.792
0.726
KI hMC3-R
0.396
0.661
0.546
0.352
0.590
0.570
0.474
Ki hMC4-R Ki hMC5-R
0.455
0.292
0.166
0.586
0.170
0.192
0.950
0.498
0.162
0.209
0.311
0.415
Bilesik KI hMC1-R KI hMC3-R KI hMC4-R KI hMC5-R
Ac-c(Cys-Glu-His-D-Z-Nal-Arg-Trp-Ala-
Cy5)-Pr0-Pro-Lys-Asp-ß-Ala-Tyr-Cly-Arg-
Lys-Gln-Lys-Arg-Arg-Arg-AIg-Arg-NH:
(SEQ 1D NO:77)
AC-c(Cys-Glu-Hls-D-Z-Nal-Arg-Trp-Ala-
Cy5)-Pr0-Pr0-Lys-Asp-ß-A1a-Tyr-G] y-Arg-
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-
Pro-Pro-Lys-Aspjjî-Ala-Tyr-Aib-Arg-Lys-
Lys-Arg-Arg-GIn-Arg-Arg-Arg-NHz (SEQ TD
AC-c(Cys-G1u-His-D-2-Nal-Arg-1-Nal-Ala-
Cys)-Pro-Pro-Arg-Asp-ß-AI a-Arg-Arg-Arg-
Arg-Arg-GIn-ATg-Arg-Arg-N Hz (SEQ ID
AC-c(Cys-Clu-His-D-Z-Nal-Arg-l-Nal-Ala-
Cys)-Pr0-Pr0-Lys-Asp-ß-Ala-Arg-Arg-Arg-
ACIC(Cy&GluýHisýDQýNaLArgýl*NalýAlaý
Cys)-Pro-Pro-Lys-Asp-ß-Ala-Arg-Arg-Arg-
AC-c(Cys-G1u -His-D-Z-Na] -Arg-Z-Nal-A] a-
CyS)-Pr0-Pro-Arg-Asp-ß-Al a-A rg-Arg-Arg-
Arg-Arg-G In-Arg-Arg-Arg-N H2 (SEQ ID
AC-c(Cys-Glu-His-D-Z-Nal-Arg-Z-Nal-Ala-
Cys)-Pro-Pro-Lys-Asp-ß-Ala-Arg-Arg-Arg-
Ac-C(Cys-C1u-I-Iis-D-2-Nal-Arg-2-Na]-Ala-
Cys)-Pr0-Pr0-Lys-Asp-_ß-Ala-Arg-Arg-Arb-
Arg-Arg-Arg-Gln-Arg-Arg-Arg-NI-Iz (SEQ ID
Ac-c(Cys-C | u-His-D-Z-Na I-Arg-Ba l -AIa-Cys)-
Pro-Pro-Arg-Asp-ß-Ala-Arg-Arg-Arg-Arg-
Arg-Arg-Gln-Arg-Arg-Arg-NHz(SEQ ID 732 1 10
Ac-c(Cys-Glu-His-D-Z-Nal-Arg-Bal-Ala-Cys)-
Arg-Gln-Arg-Arg-Arg-NI-Iz (SEQ ID NO:84)
ACIC(CysýGlu*HISIDIZINalýArgIBalýAlaýCysy
Pro-Pro-Lys-Asp-ß-Ala-Arâ-Arg-Arg-Arsö-
AC-C(Cys-Clu-His-D-Z-Nal-Arg-Trp-Ala-
Cys)-Pr0-Pro-Lys-Asp-ß-Ala-Tyr-Gly-Arg-
Lys-Lys-Arg-A rg-Arg-GI n-Arg-Arg-N Hz
(SEQ ID No:2685)
Bilesik KI hMC1-R KI hMC3-R KI hMC4-R KI hMC5-R
Ac-c(Cys-Glu-I-Iis-D-Z-Nal-Arg-Trp-Ala-
CyS)-Pro-Pro-Lys-Asp-ß-A] a-Ty r-Gly-A r g-
AC-c(Cys-Clu-His-D-2-Nal-Arg-Trp-Ala-
Lys-Lys-Arg-Arg-Arg-Arg-Arg-CJn-NHz
(SEQ ID NO:87)
AC-C(CyS-CIu-His-D-2-NaI-Arg-1-Nal-Ala-
Cy5)-Pr0-Pro-Lys-Asp-ß-Ala-Tyr-Gly-Arg-
Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NI-Iz 4-59 6-28 0-
AC-C(CyS-C I U-HîS-D-Z-Na I-Arg-BaI-AIa-Cys)-
Pro- Pro-Lys-Asp-_ß-AIa-Ty r-C Iy-Arg- Lys-
L ys-AI g-Arg-Cln-Ar g-Arg-Ar g-NH: (SEQ ID
Ac-C(Cys-Glu- His-D-Z-Nal-Arg-1-Nal-Ala-
Cys)-Pro-Pro-Lys-Asp-ß-Ala-Arg-Arg-Lys-
Arg-Arg-Gln-Arg-Arg-Arg-N Hz (SEQ ID
AC-C(Cys-G1u-His-D-2-Na1-Ar g-l ~Nal~Ala-
Cys)-Pr0-Pr0-Lys-Asp-ß-Ala-Arg-Lys-Arg-
Ar g-Arg-Gln-Arg-Ar g-Arg-NH: (SEQ 1D
Ac-C(Cys-Glu-His-D-2-Na1-Arg-2-Nal-Ala-
Cys)-Pr0-Pr0-Lys-Aspjlî-Alii-Arg-Arg-Lys-
Arg-Arg-Gln-Arg-Arg-Arg-N H2 (SEQ ID
AC-C(Cys-Gl Li-Hls-D-2-Na1-Arg-2-Nal-Ala-
Cys)-Pr0-Pr0-Lys-Asp-ß-Ala-Tyr-Gly-Arg-
A r g-Lys-A rg-Arg-Gl'n -A rg-A r g-Arg-NHz
(SEQ ID NO:90)
Ac-c(Cys-C 1u-His-D-Z-Nal-Arg-Z-Nal-Ala-
C ys)-Pr0- Pro-Lys-Asp-jÂ-Al a-Gly-Arb-Arg-
LyS-Arg-Arg-Gln-Arg-Arg-Arg-NI-Iz (SEQ ID
Ac-C(Cys-Glu- Hi s-D-Z-Na l-Arg-Z-N aI-Ala-
Cys)-Pro-Pr0-Lys-Asp-ß-Ala-Gly-Arg- Lys-
Ac-Nle-C(Cys-D-Ala-His-D-Phe-Arg-Trp-
Gln-Arg-Arg-Arg-N H2 (SEQ ID NO: 1 36)
Ac-N]e-c(Cys-D-A1a-His-D~Phe-Arg-Trp-
Arg-Arg-Arg-Arg-NHz (SEQ ID No:137)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-
Ghi-Arg-Arg-Arg-NI-IzßEQ 1D No:136)
Bilesik
ACINIeýc(CysýDýAla*HîsýDIPheýArgýTrp*
Cys)-ß-A]a-Gîy-Arg-Arg-Arg-Arg-Arg-Gln-
Arg-Arg-Arg-N H2(SEQ ID No:138)
Ac-NIe-C(Cys-D-A1a-His-D-Phe-Arg-Trp-
Arg-Arg-NH2(SEQ ID No:138)
AC-Nle-C(Cys-D-Ala-His-D-Phe-Arg-Trp-
Cys)-j$-Ala-Tyr-Gly-Arg-Arg-Arg-Arg-Arg-
Cln-Arg-Arg-AIg-NI-h (SEQ ID No:139)
AC-N]e-C(CyS-D-Ala-His-D-Phe-Arg-Trp-
Cys)-j3-Ala-Cly-Arg-Arg-Arg-Arg-Arg-Gln~
Arg-Arg-Arg-Arg-NHz (SEQ 1D No:139)
Bilesik
AC-C(Cys-Glu-His-D-Z-Nal-Arg-Z-Nal-ß-Ala-
Cys)-Pr0-Pr0-L_ys-Asp-N1-I2(SEQ 1D No:270)
AC-C(CyS-C 1 u-His-D-Z-Na]-Arg-2-NaI-Aib-
Cys)-Pr0-Pr0-Lys-Asp-NI-Iz (SEQ ID No:270)
AC-c(Cys-G1u-Hls-D-2-Nal-Arg-l-Nal-Ala-
Cys)-Pro-Pro-Lys-ASp-ß-A]a-Tyr-GIy-Arb-
Arg-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NI-Ig
(SEQ ID NO:95)
AC-C(CyS-CIu-H is-D-Z-NaI-Arg-1 -Nal-Al a-
Cys)-Pro-Pro-Lys-Asp-ß-AIa-Tyr-C ly-Arg-
Lys-Arg-Arg-Arg-Cln-Arg-Arg-Arg-NI-Ii
(SEQ ID NO:96)
AC-C(Cys-GIu-Hîs-D-2-N al-Arg-î -NaJ~AIa-
Cys)-Pro-Pro-Lys-Asp-jS-Ala-Cly-Arg-Arg-
Lys-Arg-Arg-Gln-Arg-Arg-Arg-N Hz (SEQ ID
AC-C(Cys-Glu-His-D-Z-Nal-Arb-l-Nal-Ala-
Cys)-Pro-Pro-Lys-Asp-_ß-A]a-Gly-Arg-Lys-
Arg-Arg-Arg-Cln-Arg-Arg-Arg-N Hz (SEQ ID
AC-C(Cys-Glu-His-D-2-Nal-Arg-Z-Nal-Ala-
Cys)- Pro- Pro-Lys-Asp-_ß-Ala-Arg-Lys-Arb-
Arg-Arg-Ghi-Arg-Arg-Arg-NI-Iz (SEQ 1D
Ac-c(Cys-GJu-His-D-2-N al-Arg-Z-N al-Ala-
Cys)-Pro-Pro-Lys-Asp-jS-Ala-Tyr-Gly-Arg-
NH2(SEQ ID No:101)
AC-C(CyS-Glu-His-D-2-NaI-Arg-BaI-AIa-Cys)-
Pro-Pro-Lys-Asp-ß-Ala-Arg-Lys-Arg-Arg-
Arg-Gln-Arg-Arg-Arg-NHzGEQ ID No:105)
KI hMC1-R
0.439
0.821
0.406
Tablo 6B
KI hMC3-R
KI hMC1-R Ki hMC3-R
0.604
Ki hMC4-R Ki hMC5-R
0.476
0.700
0.602
Ki hMC4-R Ki hMC5-R
0.301
0.305
0.243
0.303
0.865
0.575
Bilesik KI hMC1-R KI hMC3-R KI hMC4-R KI hMC5-R
Ac-c(Cys-Glu-Hîs-D-2-Na1-Arg-Bal-Ala-Cys)-
Pro-Pro-Lys-Asp-ß-Ala-Tyr-Gly-Arg-Arg-
Lys-Arg-Arg-CIn-Arg-Arg-Arg-NHz (SEQ 1D
Ac-c(Cys-Clu-I-Iis-D-2-Nal-Arg-Bal-Ala-Cys)-
Pro-Pro-Lys-Asp-ji-Ala-Tyr-Gly-Arg-Lys-
Arg-Arg-Arg-Gln-Arg-Arg-Arg-NH: (SEQ ID
Ac-c(Cys-G1Li-His-D-2-Na1-Arg-Bal-Ala-Cys)-
Pro-Pro-Lys-Asp-jS-Ala-Gly-Arg-Arg-Lys-
Arg-Arg-Gln-Arg-Arg-AIg-NI-li (SEQ ID
AC-C(Cys-Gl u-H is-D-2-Nal-Arg-Bal-Ala-Cys)-
AC-C(Cys-Glu-His-D-Z-Nal-Arb-Bal-Ala-Cysy
Pro-Pr0-Lys-Asp-_ß-Ala-Gly-Arg-Lys-Arg-
Arg-Arg-C ln-Arg-Arg-Arg-N Hz (SEQ [D
AC-Nle-C(Cys-D-Al a-l-lis-D-Phe-Arg-Trp-
AC-Nle-C(Cys-D-Ala-H is-D-Phe-Arg-Trp-
Gln-Arg-Arg-Arg-Nl-h (SEQ 1D N 02142)
AC-N Ie-C(Cys-D-Ala-His-D-Phe-Arg-Trp-
ArgýArgýArgýN Hz (SEQ [D No:141)
AC-NIe-C(Cys-D-Ala-l-lis-D-Phe-Arg-Trp-
Arg-Arg-Arg-N Hz (SEQ ID No:142)
Ac-Nle-C(Cys-D-Ala-His-D-Phe-Arg-Trp-
Arg-Arg-NHi (SEQ 1D No:143)
AC-N le-C(Cys-D-Ala-His-D-Phe-Arg-Trp-
Arz-Arg-NHz (SEO ID No:1441
TABLO 7 - Formül (V) Örnekleri ile ilgili Baglanma Sabitleri
Tablo 7A
Formül (V) Bilesikleri Ki hMC1 Ki hMC3 Ki hMC4 Ki hMCS
c[Hydantoin(C(O)-(Cys-D-Ala))-Hîs-D-Phe-
c[Hydantoin(C(O)-(Glu-D-Ala))-His-D-Phe-
C[Hydantoin(C(O)-(Glu-D-Ala))-His-D-Phe-
Arg-Trp-DabLNl-lz (SEQ 1D No:276)
Formül (V) Bilesikleri
c[Hydantoin(C(O)-(Glu-D-Ala))-His-D-Phe-
Arg-Trp-Dap]-NH: (SEQ [D No:276)
c[Hydant0in(C(0)-(Asp-D-Ala))-His-D-Phe-
ArgýTrpýOrnyNHi (SEQ 1D No:273)
c[Hydant0in(C(O)-(Asp-D-Ala))-l-lis-D-Phe-
Arg-Trp-Dap]-NH2 (SEQ 1D No:273)
c[Hydantoin(C(O)-(Asp-His))-D-2-Na1-Arg-
Trp-Lys]~NHz (SEQ ID No:275)
c[Hydantoin(C(0)-(Asp-Aic))-D-2-Nal-Arg-
Trp-Lys]-NH2 (SEQ ID No:275)
c[1-lydantoin(C(O)-(Asp-A5c))-D-2-Nal-Arg-
TrpýLySLNI-iz (SEQ 1D No:275)
C[Hydantoin(C(0)*(AspýAöc))ýD*2*NalýArgý
Trp-Lys]-NH: (SEQ 1D N 0:275)
C[Hydant0in(C(O)-(Asp-Apc))-D-2-Nai-Arg-
c[Hydantoin(C(O)-(Asp-A3c))-D-2-Na1-Arg-
Trp-Lys]-NHz (SEQ 1D N 0:275)
TABLO 7B - Formül (VI) Örnekleri ile ilgili Baglanma Sabitleri
Formül (VI) Bilesikleri
Hydantoin(C(O)-(NIe-G1y))-C(Cys-G1u-His-D-
Phe-Arg-Trp-Cys)-NH: (SEQ ID No:278)
Hydantoin(C(Ö)-(Gly-G1y))-C(Cys-Glu-His-D-
Phe-Arg-Trp-Cys)-NH2 (SEQ [D No:278)
Hydantoin(C(O)-(A6c-Nle))-c(Cys-D-Ala-His-
D-Phe-Arg-Trp-Cys)-NH2 (SEQ 1D No:284)
Hydantoin(C(O)-(D-A1a-Nle))-C(Cys-D-Ala-
His-D-Phe-Arg-Trp-Cys)-NH2 (SEQ TD
Hydantoin(C(O)-(Val-Nle))-C(Cys-D-AIa-His-
D-Phe-Arg-Trp-Cys)-NH: (SEQ ID No:284)
Hydantoin(C(O)-(Leu-Nle))-C(Cys-D-Ala-His-
D-Phe-Arg-Trp-Cys)-NHz (SEQ ID No:284)
Hydantoin(C(O)-(Cha-Nle))-c(Cys-D-Ala-His-
D-Phe-Arg-Trp-Cys)-NH2 (SEQ 1D No:284)
Hydantoin(C(O)-(Aib-N1e))-C(Cys-D-Ala-I-Iis-
D-Phe-Arg-Trp-CyS)-NH2 (SEQ ID NO:284)
Hyda ntoin (C(O)-(N1e-C]y))-c(Cys-D-AIa-HiS-
D-Phe-Arg-Trp-Cys)-NH: (SEQ ID No:279)
Hydantoin(C(O)-(GIy-G1y))-c(Cys-D-AIa-His-
D-Phe-Arg-Trp-Cys)-NH: (SEQ ID No:279)
Hydantoin(C(O)-(Nie-Giy))-c(Cys-D-AIa-His-
D-Phe-Arg-Trp-Pen)-NH2 (SEQ ID No:280)
>10000
>10000
Formül (VI) Bilesikleri KI hMC1 Ki hMC3 Ki hMC4 KI hMCS
Hydantoin(C(0)-(Gly-Gly))-c(Cys-D-Ala-His-
Hydantoin(C(O)-(A1a-Gly))-C(Cys-D-Ala-His-
Hydantoin(C(0)-(D-A1a-Cly))-C(Cys-D-Ala-
Hydantoin(C(O)-(Aib-Gly))-c(Cys-D-Ala-His-
Hydantoin(C(O)-(Val-G1y))-c(Cys-D-Ala-His-
Hydantoin(C(O)-(Ile-Gly))-C(Cys-D-Ala-Hls-
Hydantoin(C(O)-(Leu-Gly))-c(Cys-D-Ala-l-lis-
Hydantoin(C(O)-(D-Arg-Gly))-C(Cys-Glu-I-Iis-
Hydantoin(C(O)-(Gly-D-Arg))-c(Cys-G1u -His-
Hydantoin(C(O)-(Arg-Cly))-C(Cys-G1u-His-D-
Hydantoin(C(O)-(Gly-Arg))-c(Cys-Glu-His-D-
Hydantoin(C(O)-(Arg-Gly))-C(Cys-D-Ala-His-
Hydantoin(C(O)-(D-Arg-G]y))-C(Cys-D-Ala-
Hydantoin(C(O)-(C1y-D-Arg))-C(Cys-D-Ala-
N0288)
Hydantoin(C(O)-(Gly-Arg))-c(Cys-D-Ala-His-
D-2-NaI-Arg-Trp-CyS)-N Hz (SEQ ID No:282)
TABLO ?C - Formül (VII) Örnek_leri ile ilqili _Baglanma Sabitleri
Formül (VII) Bilesikleri Ki hMC1 Ki hMC3 Ki hMC4 Ki hMC5
c[Hydantoin(C(0)-(Aib-Cys))-D-Ala-His-D-
C[Hydantoin(C(0)-(Val-Cys))-D-A1a-His-D-
C[Hvdantoin(C(0)*(Leu*C\/s))ýDýAlaýHisýDý
Phe-Arg~Trp-Cys]-NH2 (SEQ ID NO:290)
Formül (VII) Bilesikleri KI hMC1 Ki hMC3 Ki hMC4 Ki hMC5
c[Hydantoin(C(O)-(lle-Cys))-D-Ala-l-lis-D-Phe-
Phe-Arg-Trp-Cys]-NH2 (SEQ 1D NO:290) ' '
Arg-Trp-Cys]-NI-12 (SEQ ID No:291)
TABLO 8- Secilen Bilesikler için Ra_dvoligand Baglanma Deneyi Verileri
Bilesik Ki hMC1-R Ki hMC3-R Ki hMC4-R Ki hMCS-R
Ac-Tyr-Arg-c(Cys-D-Ala-His-D-Phe-
AC-2-Nal-Arg-C(Cys-D-Ala-l-lis-D-Phe-
Arg-Trp-Cys)-NH2 (SEQ TD No:292)
AC-l-Nal-Arg-c(Cys-D-Ala-His-D-Phe-
Arg-Trp-Cys)-NH2 (SEQ lD No:292)
Ac-Phe-Arg-c(Cys-D-Ala-His-D-Phe-
Ac-Trp-Arg-C(Cys-D-Ala-His-D-Phe-
Arg-Trp-Cys)-NH2 (SEQ 1D No:292)
Ac-Pff-Arg-c(Cys-D-AI a-l-lis-D-Phe-
Melanokortini'n Fonksiyonel Aktivitesi ve Seçici/igi
Mevcut patent hakki bildiriminin bilesikleri görece diger melanokortin reseptörlerine göre
tercihli bir sekilde (bir diger deyis ile seçime bagli olarak) MC-4 ile etkilesime girecektir.
Bilesiklerin insanlara veya diger hayvanlara verildigi durumlarda bu bilesiklerin verilmesi ile
baglantili yan etkilerin minimum düzeye indirmek için, seçicilik özellik ile önemlidir. Bilesigin
MC-4 seçiciligi burada, MC-1 reseptörü (EC50 -MC-1) ile ilgili bilesigin EC50 degerinin MC-3
reseptörü ile ilgili bilesigin E050 degerine orani olarak tanimlanir (E/MC-4 (EC50 -
MC-4), EC50 degerleri yukarida tarif edildigi gibi ölçülür. Formüller asagida belirtildigi gibidir:
MC 3 sclectiîîiity - [ECM MC II/[ECn'i MC 3]
MC 4 sclccti'îiiti/ - [ECrii'i MC Jl/[ECm ML.` 4]
Burada tanimlanan bilesik, yukarida belirtilen “MC-3 seçilebilirlik” orani en az yaklasik 10,
tercihli bir sekilde en az yaklasik 100 ve daha da tercih edilen durumda en az yaklasik 500
oldugunda “MC-3 reseptörü için seçici” olarak tanimlanir.
Burada tanimlanan bilesik, yukarida belirtilen “MC-4 seçilebilirlik” orani asgari 10, tercihli bir
sekilde asgari 100 ve daha da tercih edilen durumda asgari yaklasik 500 oldugunda “MC-4
reseptörü için seçicidir".
Teknikte uzman kisiler, bildirim bilesiklerinin melanokortin reseptörü moleküllerine baglanma
aktivitelerini tahlil etmek için burada tarif edilenlere benzer prosedürlerin kullanilabilecegini
sik/ik AMP Biyo-anali'zi
Hücre içi siklik AMP (cAMP) seviyeleri elektrokemilüminesans (ECL) analizi ile (Meso Scale
Discovery®, Gaithersburg, MD; bundan böyle MSD olarak anilacaktir) tespit edilmistir. Sabit
sekilde hMC reseptörü alt türlerini ifade eden CHO-K1 hücreleri RMPI 1640® analiz tampon
maddesinde süspansiyona alinmistir (RMPI 1640 tampon maddesi 0.5 mM
izobütilmetilksantin (IBMX) ve % . Sabit
sekilde hMC reseptörü 1, 3, 4 veya 5 alt türlerini ifade eden transjenik CHO-K1 hücreleri
entegre karbon elektrotlar içeren ve anti-CAMP antikor ile kapli 384-kuyulu Multi-Array®
plakalarda (MSD) yaklasik 7,000 hücre/kuyu yogunlukta dagitilmistir. Artan yogunlukta test
bilesikleri ilave edilmis ve hücreler yaklasik 37°C 'de yaklasik 40 dakika süre ile inkübe
edilmistir. Bu inkübasyonun ardindan, % 0.2 protein kokteyli ve 2.5 nM TAGTM rutenyum
etiketli cAMP (MSD) içeren Iizis tamponu (HEPES-tamponlu salin çözelti ve ph 7.3 degerde
MgCIg ve Triton X-100®) ilave edilmis ve hücreler oda sicakliginda yaklasik 90 dakika inkübe
edilmistir. Ikinci inkübasyon süresinin sonunda okuma tamponu (pH 7.8 degerde ECL ortak
reaktant ve Triton X-100 içeren Tris tamponlu çözelti) ilave edilmis ve hücre lizatlarindaki
cAMP seviyeleri Sector Imager ile ECL tespit edilerek aninda
belirlenmistir. Veriler bilgisayar destekli dogrusal olmayan regresyon analizi (XL fit; IDBS)
kullanilarak analiz edilmis ve EC50 degeri veya Kb degeri olarak rapor edilmistir.
E050 maksimum reaksiyon tepkisinin % 50 'sini elde edebilmek için örnegin, yukarida tarif
edilen analiz konularak belirlenen maksimum cAMP seviyesinin % 50 'si gibi, gereken
agonist bilesik yogunlugunu temsil eder. Kb degeri antagonistin tesirini yansitir ve Schild
analizi ile belirlenir. Kisaca, agonistin yogunluk tepki egrileri artan yogunluklarda antagonistin
bulundugu durumlarda gerçeklestirilir. Kb degeri, agonisit ile ilgili yogunluk tepki egrisinde 2
kat kayma yaratan antagonist yogunlugudur. Bu deger, Schield grafiginde çizgiyi Y
ekseninde sifirlanmasi ile hesaplanir.
Seçilen bilesikler yukarida ele alinan analizler kullanilarak test edilmis ve Tablo 9, 10, 11 ve
12 'de raporlanmistir.
TABLO 9 - Seçilen Bilesiklerin cAMP Biyo-analiz Verileri
Tablo 9A
hMC1-R hivics-R hMC4-R hMCS-R R/IVIC4-R SEQ'DNOî
Bilesik
Ac-Arg-C(Cys-D-
Arg-Trp-Cys)-N Hz NO:50
Ac-D-Ärg-CKIys-D-
Arg-Trp-Cys)-NH2
Ac-D-Arg-c(Cys-D- 8 E ID
Arg-Trp-Pen)-NH2 NO:51
Ac-D-Arg-c(Cys-
Trp-Gaba-Pen)-N Hz '
Ac-Arg-c(Cys-His- SE ID
Cuba-Pen)-N Hz '
Ac-Arg-c(Cys-D-
Arg-Trp-Pen)-NI-]2 '
Ac-D-Arg-C(Asp-
Trp-A1a~Lys)-NHi '
Ac-Arg-C(Asp-His- SE ID
A]a-Lys)-NH2 '
ND = belirli degil
Bile ik EC50 EC50 ECSO EC50 ECsohMC'î-R SEQ ID
AC-NIe-C(Cys-D-Ala-His- SE Q ID
D-Phe-c(Cys-His-D- S
D-Cys)-Thr-NH2 '
NJe-C(Cys-His-D-Phe- SEQ ID
Nle-c(Cys-His-D-Phe- SEO ID
Bilesik
Ac-NIe-c(Asp-Hi s-D-
Phe-Arg-Trp-ß-A] a-Lys)-
AC-N Je-c(Cys-His-D-Phe-
Arg-Trp-Apn-CyS)-NH2
Ac-Cha-c(Asp-Hi s-D-
Phe-Arb-Trp-Caba-Lysy
Ac-NIe-c(Asp-Hi s-D-
Phe-Arg-Trp-Gaba-Lys )-
Ac-hCha-c(Asp-His-D-
Phe-Arg-Trp-Gaba-Lys)-
AC-N] e-c(Pen -D-AI a-His-
D-Ph e-Arg-Trp-Cys)-
AC-N le-C(Cys-D-Ala-His-
D-Phe-Arg-Trp- Pen )-
D-Phe-c(Cys-His-D-
(Et)Tyr-hArg-Trp-ß-Ala-
D-Cys)-Th r-N Hz
D-Phe-c(Cys-His-D-
(Et)Tyr-h Arg-Bip-ß-Aîa-
D-Cys)-Thr-NI-12
Ac-N le-C(Asp-D-Ala-His-
D-Phe-Arg-Bal-Lvs)-NH2
Ac-N le-c(Cys-D-Leu-His-
D-Phe-Arg-Trp-Cys)-
Ac-N Ie-c(Cys-D-Ch a-
Hi' s-D-Ph e-Arg-Trp-Cys)-
ND = belirli degil
Bilesik
Ac-Nle-c(Cys-D-Ala-His-D-2-
Naî-Arg-Trp-Cys)-NH2
AC-Nle-C(Asp-His-D-2-Nal-Arg-
Trp-Ala-Lys)-NHz
AC-NJe-c(Asp-His-D-Z-Nal-Arg-
Trp-ß-Ala-Ly s)-1\'Hz
Ac-Nle-c(Cys-I lis-D-Z-Nal-Arg-
Trp-Gaba-Cys)-1\'Hz
ND 1.89 0.531 ND ND NO:21
EC50 hMC Kb Kb MC4- EC50hMCS- SEO ID
1-R hMCB-R R R NO:
Bile ik EC50 hMC Kb Kb MC4- EC50hMC5- SEQ ID
s 1-R hMCS-R R R NO:
AC-Nle-C(Cys-His-D-2-Nal-Arg- SEO ID
AC-hPhe-C(Asp-His-D-2-Nal-Arg- SEO ID
Ac-Cha-C(Asp-His-D-2-Nal-Arg- SEO ID
Ac-Nle-c(Cys-D-AIa-His-D-2- SEQ ID
Tablo 9D
Bilesik EC50 hMC1-R Kb hMC3-R Kb MC4-R EC50hMC5-R SEQ ID NO:
Ac-Arg-C(Cys-D-Ala-His-D-Z- SEQ lD NO:
Bilesik ECsohMC1-R Kb hMC3-R Kb hMC4-R ECSO hMCS-R
Ac-c(Cys-Glu-His-D-Z-Nal-Arg-Trp-A1a-
Cys)-Pro-Pro-Lys-Asp-NHz (SEQ TD
Tyr-Cly-Arg-Lys-Lys-Arg-Arg-Cln-Arg-
Arg-Arg-Nle-c(Asp-His-D-Z-Nal-Arg-Trp- N D 4500 1 05 N D
Lys)-N Hz (SEQ ID NO:60)
Tyr-GIy-Arg-Lys-Lys-Arg-Arg-Gl'n-Arg-
Arg-Arg-Doc-NIe-c(Asp-His-D-Z-Na l-Arg- N D 395 16.8 N D
Trp-Lys)-NH2 (SEQ 1D NO:61)
N] e-c(Asp-His-D-2-Na1-Arg-TTp-LySk/X-
Ala-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln- N D 207 1 8.5 N D
Ac-NIe-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-j3-
A1 a-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-GI n- N D 220 4.07 N D
Arg-Arg-Arg-Nl-h (SEQ 1D NO:62)
H-Nle-c(Asp-His-D-2-Nal-Ai-g-Trp-Lys)-
Doc-Doc-Tyr-Cly-Arg-Lys-Lys-Arg-Arg- N D 261 3. 1 1 N D
CIn-Arg-Arg-Arh-NHz (SEQ 1D NO:63)
AC-N Ie-C(Asp- H is-D-Z-Na I-Arg-Trp-Lys)-
Pro- Pro-Lys-Asp-Ty r-Cly-Arg-Lys-Lys-
Arg-AIb-Cln-Arg-Arg-AIg-NI-Iz (SEQ ID
AC-C(Cys-Glu-His-D-2-Na l -Ar g-Trp-Gl y-
Cys)-Pr0-Pr0-Lys-Asp-Tyr-Gly-Arg-Lys-
Lys-Arg-Arg-Gln-Arg-Arg-Arg-N H2 (SEQ
1D NO:65)
Ac-Nle-c(Asp-His-D-Z-Nal-Arg-Trp-LysHS-
Ala-_ S-Ala-Tyr-Gly-Arg-Lys-Lys-Arg-Arg- 1 .39 16.2 7.94
ND 14.1 22.8 ND
ND 233 26.0 ND
Bilesik EC50hMC1 -R Kb hMC3-R Kb hMC4-R EC50 hMC5-R
AC-Nle-C(Asp-His-D-2-Nal-Arg-Trp-Lys)-
Pro-Pro-Lys-Asp-Doc-Tyr-GIy-Arg-Lys-
Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH: (SEQ
Ac-c(Cys-G]u-His-D-Z-Nal-Arg-Trp-Gly-
Cys)-Pr0-Pr0-Ly s-Asp-DOC-Ty r-C] y-Arg-
L ys-Lys-Arg-Arg-G In -Arg-Arg-Ar g- N Hz
(SEQ ID NO:68)
Ac-c(Cys-GlLi-His-D-Z-Nal-Arg-Trp-Ala-
CyS)-Pr0-Pro-Lys-Asp-ß-AIa-Tyr-GIy-Arg-
NHz(SEQ 1D NO:69)
Ac-c(Cys~Glu-His-D-2-Nal~Arg-Trp~Ala-
Cys)-Pro-Pro-Lys-Asp-Doc-Tyr-Cly-Arg-
Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH:
(SEQ ID NO:69)
Ac-c(Cys-Glu-His-D-Z-Nal-Arg-Z-Nal~Ala-
Ac-c(Cys-Gl Li-His-D-Z-Nal-Arg-1-Nal-Ala-
AC-C Cys-Glu-His-D-Z-NaI-Arg-Bal-Ala-
AC-N le-C(Asp- H is-D-2-Nal-Arg-Trp-Lys)-
Gln-Arg-Arg-Arg-NH2 (SEQ 1D NO:70)
ACIC(CySIGIUIHISIDIZ*NalýArgýBalýAlw
Cys)-Pro-Pro-Lys-AspIß-AIa-Arg-Arg-Arg-
Arg-Arg-Gln-Arö-Arg-Arg-NHz (SEQ ID
Ac-c(Cys-Glu-His-D-Z-Nal-Arg-Bal-Ala-
Cys)-Pr0-Pr0-Lys-Asp-ß-A] a-Gl y-Arg-Arg-
Arg-Arg-Arg-Gln-Arg-Arg-Arg-N Hz (SEQ
1D NO:73)
Ac-c(Cys-Clu-Hls-D-2-Nal-Arg-Bal-Ala-
Cys)-Pr0-Pro-Lys-Asp-ß-AIa-Tyr-Aib-Arg-
Lys-Lys-Arg-Arg-Glri-Arg-Arg-Arg-NI-Iz 67'1 439 46'
Ac-C(Cys-G1u-His-D-Z-Nal-Arg-î -Nal-A] a-
Cys)-Pr0-Pro-Arg-Asp-jS-Ala-Arg-Arg-Arg-
Arb-Arg-Gln-Arg-Arg-Arg-NHz (SEQ ID 144 1 16 893
Ac-C(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-
Cys)-Pr0- Pro-Lys-Asp-ß-AIa-Arg-Arg-Arg-
Arg-Arg-Gln-Arg-Arg-Arg-NI-Iz (SEQ ID
AC-C(Cys-Gîu-His-D-Z-NaI-Arg-1-NaI-Ala-
Cys)-Pr0-Pr0-Lys-Asp-ß-Ala-Arg-Arg-Arg-
Ar g-Arg-Arg-GIn-Arg-Arg-Arg-N Hz (SEQ
ND 17.7 1.49 ND
Bilesik EC5Üh MC1 -R Kb hMC3-R Kb hMC4-R EC50 hMCS-R
Ac-C(Cys-Glu-His-D-Z-Nal-Arg-Z-Nal-Ala-
Cys)-Pr0-Pro-Arg-Asp-jJ-AIa-Arg-Arg-Arg-
Arg-Arg-G]ri-Arg-Arg-Arg-NHz (SEQ TD
Ac-c(Cys-Clu-His-D-Z-Nal-Arg-Z-Nal-Ala-
Cys)-Pro-Pro-Lys-Asp-ß-AIa-Arg-Arg-Arg-
Arg-Arg-Gln-Arg-Arg-Arg-NI-Iz (SEQ ID
AC-C(Cys-C| u-His-D-Z-Na I-Arg-Z-NaI-Ala-
Cys)-Pro-Pro-Lys-Aspjfß-AIa-Arg-Arg-Arg-
Arg-Arg-AIg-Gln-Arg-Arg-Arg-NI-Iz (SEQ
AC-C(Cys-Glu-HiS-D-Z-Na I-Arg-Bal-Ala-
Cys)-Pro-Pro-Arg-Asp-_ß-Ala-Arg-Arg-Arg-
Arg-Arg-Arg-GIn-Arg-Arg-Arg-N Hz (SEQ
AC-C(Cys-Glu-HiS-D-Z-Nal-Arg-Bal-Ala-
Cys)-Pr0-Pro-Arg-Asp-jS-AlL-i-Arg-Arg-Arg-
Arg-Arg-CIn-Arg-Arg-Arg-NH: (SEQ ID
Ac-C(Cys-Glu-His-D-Z-Nal-Arg-Bal-Ala-
Cys)-Pro-Pro-Lys-Asp-ß-AIa-Arg-Arg-Arg-
Arg-Arg-Arg-GIn-Arg-Arg-Arg-NH: (SEQ
1D NO:83)
Ac-c(Cys-Glu-His-D-2-Na]-Arg-l-Nal-Ala-
Cyâ)-Pro-Pro-Lys-AspjS-Ala-Arg-Arg-Lys-
ArgýArgýGlnýArgýArgýArgýN Hz (SEQ ID
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-NaI-Ala-
Cys)-Pro-Pro-Lys-Aspß-Ah-Arg-Lys-Arg-
Arg-Arg-Gln-Arg-Arg-Arg-NI-Iz (SEQ ID 33-1 65-1 1 5-3
Ac-c(Cys-GIu-His-D-Z-Nal-Arg-2-Nal-Ala-
Cys)-Pro-Pr0-Lys-Asp-ß-Ala-Arg-Arg-Lys-
Arg-Arg-GJn-Arg-Arg-Arg-NHz (SEQ ID
AC-C(Cys-Glu-His-D-2-N aJ-Arg-2-N 'al-Ala-
Cys)-Pro-Pro-Lys-Asp-ß-AIa-Tyr-Cly-Arg-
Arg-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NH:
(SEQ 1D NO:90)
Ac-C(Cys-Glu-I-Iis-D-2-Nal-Arg-2-Nal-Ala-
Cys)-Pr0-Pr0-Lys-Asp-ß-Ala-Cly-Arg-Arg-
Lys-Arg-Arg-Gln-Arg-Arg-Arg-NI-Iz (SEQ
Ac-c(Cys-Glu-His-D-2-Na1-Arg-2-Nal-Ala-
Cys)-Pro-Pro-Lys-Asp-ß-AIa-GIy-Arg-Lys-
Arg-Arg-Arg-Gln-Arg-Arg-Arg-NI-h (SEQ
Ac-Nle-C(Cys-D-Ala-His-D-Phe-Arg-Trp-
Gln-Arg-Arg-Arg-Nl-lz (SEQ 1D NO: 139)
Bilesik EC50hMC1 -R Kb hMC3-R Kb hMC4-R EC50 hMC5-R
Ac-c(Cys-Glu-His-D-2-Na1-Arg-2-Nal-A1a-
Cys)-PrO-Pro-Lys-Asp-ß-AIa-Tyr-CIy-Arg-
Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NI-L
(SEQ 1D NO:71)
AC-C(Cys-Clu-His-D-2-Nal-Arg-Trp-Ala-
Cys)-Pr0-Pr0-Lys-Asp-ßAla-Tyr-Cly-Arg-
Lys-Lys-Arg-Gin-Arg-Arg-Arg-Arg-NH:
(SEQ ID NO:75)
Ac-C(CyS-CIu-His-D-2-Na l-Arg-Trp-Ala-
Cys)-Pr0-Pro-Lys-Asp-ß-Ala-Tyr-Gly-Arg-
Lys-Lys-GIn-Arg-Arg-Arg-Arg-A rg-N Hz
(SEQ 1D NO:76)
Ac-c(Cys-GIu-His-D-2-NaI-Arg-Trp-Ala-
Cys)-Pr0-Pro-Lys-Asp-ß-Ala-Tyr-Gly-Arg-
Lys-Gln-Lys-Arg-Arg-Arg-Arg-Arg-NHz
(SEQ ID NO:77)
AC-C(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-
Cys)-Pro-Pro-Lys-Asp-_ß-Ala-Tyr-Cly-Arg-
Lys-Lys-Arg-A rg-Arg-A rg-Gi n-A rg-NHz
(SEQ ID NO:78)
Ac-c(Cys-Glu-His-D-Z-Nal-Arg-Trp-Ala-
CyS)-P ro-Pro-LyS-Asp-ß-AIa-Tyr-GIy-Arg-
Lys-Lys-Arg-Arg-Arg-CIn-Arg-Arg-N Hz
(SEQ ID NO:85)
AC-c(Cys-GlLi-His-D-2-Na1-Arg-Trp-Ala-
Cys)-Pro-Pro-Lys-Asp-_ß-Ala-Tyr-Gly-Arg-
Gin-Lys-Lys-Arg-Arg-Arb-Arg-Arg-NHz 12'0 13'7 9'38
AC-C(CyS-Clu-His-D-2-Nal-Arg-Trp-Ala-
CyS)-Pr0-Pro-LyS-ASp-ß-Ala-Tyr-Cly-Arg-
NH2(SEQ ID NO:87)
Ac-c(Cys-Clu-His-D-Z-Nal-Arg-1-NaI-Ala-
Cys)-Pr0-Pro-Lys-Asp-jS-Ala-Tyr-Gly-Arg-
Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-NI-L 43'3 215 5'87
Ac-c(Cys-GIu-His-D-2-Nal-Arg-BaI-Ala-
Cys)-Pro-Pro-Lys-Asp-ji-AIa-TypcIy-Arg-
Lys- Lys-Arg-Arg-C In-Arg-Arg-Arg-N Hz
(SEQ ID NO:71)
ND = belirli degil
Tablo 10B
Bile ik EC50 EC50 EC50 EC50
AC-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-
Cys)-(Doc)2-Tyr-Gly-Arg-Lys-Lys-Arg-
Bilesik
Ac-Nle-C(Cys-D-Ala-His-D-Phe-Arg-Trp-
Cys)-_ß-Ala-Tyr-Gly-Arg-Lys-Lys-Arg-Gln-
Arg-Arg-Arg-Arg-NHz (SEQ 1D No:137)
Ac-Nle-c(Cys-D-Aia-Hi's-D-Phe-Arg-Trp-
Cys)-j3-Ala-Gly-Arg-Arg-Arg-Arg-Arg-Gln-
Arg-Arg-Arg-Nl-lz (SEQ 1D NO: 1 36)
Ac-Nle-C(Cys-D-Ala-His-D-Phe-Arg-Trp-
Cys)-_13-Ala-Arg-Arg-Arg-Arg-Arg-Gln-Arg-
Ark-Arg-NHz (SEQ 1D No:138)
Bilesik
Ac-c(Cys-G1u-Hi s-D-2-Na 1 -Ar g-Z-Nal -ß-
AIa-Cys)-Pro-Pro-Lys-Asp-NH: (SEQ TD
N 02270)
AC-C(Cys-Gl u-His-D-Q-Nal -A rg-Z-NaI-Ai b-
Cys)-Pr0-Pro-Lys-Asp-NH2 (SEQ ID
Ac-C(Cys-Glu-His-D-2~Nal-Arg-1~Nal~Ala-
Cys)-Pro-Pr0-Lys-Asp-_ß-Ala-Tyr-Gly-Arg-
Arg-Lys-Arg-Arg-G In-Arg-Arg-Arg-N Hz
(SEQ ID NO:95)
Ac-c(Cys~G1u-His-D-2-Na1-Arg-1 ~Nal-A]a~
Cys)-Pro-Pr0-Lys-Asp-ß-Ala-Tyr-Cly-Arg-
Ly s-Arg-Arg-Arö-Cln-Arg-Arg-AIg-N H:
(SEQ ID NO:96)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-i -Nal-Ala-
Cys)-Pro-Pr0-Lys-Asp:IS-Ala-Gly-Arg-Arg-
LyS-Arg-Arg-GIn-Arg-Arg-Arsj-N Hz (SEQ
1D NO:97)
ACIC(CySIGliiýHisýDQýNalýAr 5,1 *NalýAla*
CyS)-PrO-PrO-LyS-Asp-ß-Ala-Gly-Arg-Lys-
Arg-Arg-Arg-Gln-Arg-Arg-Arg-NI-h(SEQ
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-
Cys)- Pro- Pro-Lys-Aspîii-Ala-Arg- Lys-Arg-
Arg-Arg-Gln-Arg-Arg-Arg-NI-Iz (SEQ ID
Ac-c(Cys-Clu-His-D-2-N al-Arg-Z-N 'al-Ala-
Cys)-Pro-Pr0-Lys-Asp-ß-A]a-Tyr-Gly-Arg-
Lys-Arg-Arg-Arg-Gln-Arg-Arg-Arg-N Hz
(SEQ ID No:101)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-BaI-Ala-
Cys)-Pro-Pro-Lys-Asp-ß-Ala-Arg-LyS-Arb-
Arg-Arg-Cln-Arg-Arg-Arg-NI-Iz (SEQ ID
0.481
ECsohMC1-
0.964
Kb hMC3- Kb hMC4- ECsohMC5-
Büegk R
AC-C(Cys-Glu-His-D-Z-Nal-Arg-Bal-Ala-
Cys)-Pr0-Pro-Lys-Asp-ß-Ala-Tyr-Gly-Arg-
NH2(SEQ ID No:100)
Ac-c(Cys-Glu-His-D-Z-Nal-Arg-Bal-Ala-
Cys)-Pr0-Pro-Lys-Asp-ß-Ala-Tyr-Gly-Arg-
Lys-Arg-Arg-Arg-Gln-Arg-Arg-Arg-NHz
(SEQ 1D No:101)
Ac-c(Cys-G1u-His-D-2-Na1-Arg-Bal-Ala-
Cys)- Pro-Pro-Lys-Asp-ß-Ala-Cly-Arg-Arg-
Lys-AIg-Arg-Ghi-Arg-Arg-Arg-NI-b (SEQ
1D NO:102)
AC*C(CySIG1LIIHISIDý2ýN alýArgýBalýAlaý
Cys)ýProýProýLysýAspîßýAlaýArgýArgýLysý
Arg-Arg-Cln-Arg-Arg-Arg-NHzßEQ ID
Ac-c(Cys-G1u-His-D-Z-Nal-Arg-Bal -Ala-
Cys)-Pr0-Pr0-Lys-Asp-ß-Ala-Gly-Arg-Lys-
Arg-Arg-Arg-C1n-Arg-Ar g-Arg-NHz (SEQ
1D N O: 1 03)
ND = belirli degil
Bilesik EC50
Ac-NIe-c(Cys-D-AIa-His-D-Phe-Arg-Trp-
CyS)-ß-AIa-Tyr-Gly-Arg-Arg-Lys-Arg-Arg-
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Ai'g-Trp-
C ys)-_ß-Ala-Tyr-Gly-Arg-Lys-Arg-Arg-Arg- 7.57
GlnýArgýArgýArgýNl-Iz (SEQ 1D No:142)
Ac-Nle-c(Cys-D-A1a-His-D-Phe-Arg-Trp-
Cys)-ß-Ala-Gly-Arg-Arg-Lys-Arg-Arg-
AC-Nle-C(Cys-D-A1'a-HiS-D-Phe-Arg-Trp-
CysHÃIAla7G]yýArgýLysýArgýArgýArg* 2, 81
GIn-Arg-Arg-Arg-NH: (SEQ ID No:142)
AC-Nle-C(Cys-D-A1a-His-D-Phe-Arg-Trp-
CyS)-j3-A1a-Arg-Arg-LyS-Arg-Arg-Gln- 1 _ 86
Arg-Arg-Arg-NHZ (SEQ 1D No:143)
AC-Nle-C(Cys-D-A1a-His-D-Phe-Arg-Trp-
Cys)-ß-AI a-Arg-Lys~Arg-Arg-Arg-CIn- 206
Ai'g-Arg-Arg-NHz (SEQ ID No:144)
ECsohMC1-
0.422
0.600
0.260
0.298
0.367
0.394
Kb hMC3- Kb hMC4- EC50hMCS-
TABLO 11 - Formi_il (1) Örneklerivle ilgili Hi_icre ici Siklik A_MP (cA_MP) Seviyeleri
Tablo 1 1 A
Formül (V) Bilesikleri EC50hMC1 ECsohMCS EC50hMC4 ECsohMCS
C[Hydantoin(C(O)-(Cys-D-Ala))-His-D-Phe- 218 5 42
Arg-Trp-Cys]-NI-Ii (SEQ ID No:271) ' ' '
C[Hydantoin(C(O)-(Glu-D-Ala))-His-D-Phe- 22 3 3 62
Arg~Trp-Lys]-NH2 (SEQ lD No:276) - ` ' -
C[Hydant01n(C(O)-(GILi-D-Ala))-His-D-Phe- 39 2 4 9 4
Arg-Trp-Om]-NH2 (SEQ lD No:276) - ' ` -
C[Hydan toin(C(O)-(Glu-D-AIa))-His-D-Phe-
c[Hydantoin(C(O)-(Asp-D-Ala))-His-D-
C[Hydant0in(C(O)-(Asp-D-Ala))-His-D- _ 49 3 2 12 _
Phe-Arg-Trp-Dap]-NHz (SEQ ID No:273) ' '
Formül (VI) Bilesikleri ECsohMC1 ECsohMCS ECsohMC4 ECsohMCS
Hydantoin(C(O)-(Nle-Gly))-c(Cys-Glu-His-
Hydantoin(C(O)-(G1y-Gly))-c(Cys-Glu-His- >
Hydantoin(C(O)-(A6C-NlB))-C(Cys-D-A_la-
HisýDýPheýArgýTrpýCys)INH2 (SEQ 1D - 4.89 1 .80 -
Hydantoin(C(O)-(D-Ala-Nle))-c(Cys-D-Ala-
His-D-Phe-Arg-Trp-Cys)-NHz (SEQ ID - 2.56 1 .47 -
Hydantoiri(C(O)-(Va1-N1e))-c(Cys-D-A1a-
His-D-Phe-Arg-Trp-Cy5)-NT-l2 (SEQ TD - 4.61 0.977 -
Hydantoin(C(O)-(Leu-N1e))-c(Cys-D-Ala-
His-D-Phe-Arg-Trp-Cys)-NHi (SEQ ID - 9.68 1.83 -
Hydantoin(C(O)-(Cha-Nle))-c(Cys-D-Ala-
His-D-Phe-Arg-Trp-Cys)-NI-h (SEQ 1D - 9.97 13.9 -
Hydantoin(C(O)-(Cly-Gly))-c(Cys-D-Ala-
Hydantoin(C(O)-(N 1e-G1y))-C(Cys-D-Ala-
Hydantoin(C(O)-(C]y-C1y))-C(Cys-D-Ala-
Formül (VI) Bilesikleri EC50hMC1 EC50hMC3 EC50hMC4 ECsohMCS
Hydantoîn(C(O)-(Ala-Gly))-C(Cys-D-Ala-
Hyda 11 to] n (C(O)-(D-Ala-GIy))-c(Cys-D-Al a-
Hydantoin(C(O)-(D-Arg-G1y))-c(Cys-G1Li-
Hydantoin(C(O)-(Cly-D-Arg))-C(CyS-Glu-
Hydantoin(C(0)-(Arg-Gly))-C(Cys-G1u-His-
Hydantoin(C(O)-(Gly-Arg))-c(Cys-Glu-l-lis-
D-Phe-Arg-Trp-CysyNHz (SEQ 1D No:285)
Hydantoin(C(O)-(AIg-Gly))-c(Cys-D-A1a-
Hydantoin(C(0)-(D-Arg-G1y))-C(CyS-D-
Hydantoi'n(C(O)-(C]y-D-Arg))-C(Cys-D-
Hyda ntoi'n(C(O)-(GIy-Arg))-c(Cys-D-Ala-
Hydanto'm(C(O)-(Arg-Cly))-c(Cys-D-Ala-
TABLO 11C
Formül (VII) Bilesikleri ECsohMC1 ECsohMC3 EC5ohMC4 ECsohMCö
c[Hydantoin(C(O)-(Aib-Cys))-D-Ala-His-D-
Phe-Arg-Trp-Cys]-NI-Ii (SEQ ID No:290)
C[Hydantoin(C(O)-(VaI-Cys))-D-A1a-His-D-
Phe-Arg-Trp-Cys]-NH: (SEQ ID No:290)
C[Hydantoin(C(O)-(Leu-Cys))-D-AIa-His-D-
Phe-Arg-Trp-Cys]-NI-Iz (SEQ ID No:290)
C[Hydantoln(C(O)-(Ile-Cys))-D-Ala-His-D-
Phe-Arg-Trp-Cys]-NH2 (SEQ ID No:290)
c[Hydantoin(C(0)*(A6cýCys))ýDýAlaýI-IISIDI
Phe-Arg-Trp-Cys]-NH2 (SEQ ID No:290)
C[Hydantoin(C(O)-(Gly-Cys))-Glu-His-D-
Phe-Arg-Trp-Cys]-NI-12 (SEQ ID NO:291)
6.28 0.407 -
- 3.77 0.214 -
- 4.72 0.428 -
- 8.51 1.85 -
- 5.66 1.72 -
TABLO 12 Secilen Bilesiklerle ilgili -cA_MP ßivo-analiz Verileri
Bilesik EC5OhMC1-R ECsohMCS-R EC50hMC4-R EC50hMC5-R
Ac-Ty r-Arg-c(Cys-D-Al 3- H i s-D-
AC-2-NaI-Arg-c(Cys-D-Ala-His-D-
Ac-l-Nal-Arg-C(Cys-D-Ala-His-D-
Ac~Trp-Arg~c(Cys-D-Ala-His-D-
V_ücut ici (In Vivo) Çalismalari
Mevcut patent hakki bildiriminin bilesiklerinin asagidaki prosedürlere uygun olarak, insülin
direnci ve /veya vücut agirligi üzerindeki etkisi test edilebilir ve edilmistir. Teknikte uzman bir
kisi, patent hakki bildirimi bilesiklerinin insülin direnci ve / veya vücut agirligi üzerindeki
etkisini tahlil etmek için burada tarif edilenlere benzer prosedürlerin kullanilabilecegini
bilecektir.
Vücut Içi (in Vivo) çalismalariyla test edilen melanokortin reseptörleri aktive edici Iigand
bilesikleri asagidakilerdir (Tablo 13):
Ligand Kodu Yapi
Bilesik A Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NHz SEO ID NO:50
Bilesik B Hidantoin(C(O)-(Arg-Gly))-c(Cys-GIu-His-D-Phe-Arg-Trp-Cys)-NHz (SEO ID No:278)
Sprague Dawley cinsi erkek siçanlar (250 9) ayri kafeslerde ve 12 : 12 saat aydinlik :
karanlik kosullarda tutulmustur. Siçanlar, deney baslamadan önce 18 saat süre ile aç
birakilmis, hayvanlara istenildigi kadar su verilmistir. 0 zamaninda, siçanlara 100 nmoI/kg
dozda seçilen bilesikler deri altina (sc) enjekte edilmis veya tasiyici ile ve yiyecekler ile
birlikte verilmistir. Enjeksiyondan yaklasik 2, 4 ve 6 saat sonra bireysel besin tüketimi
ölçülmüstür. Patent hakki bildiriminin seçilen bilesikleri ile ilgili veriler Sekil 1 'de rapor
edilmistir.
Kronik besleme deneyleri
veya yüksek yag içeren diyet (400 g; Research Diets 12451) ile beslenen Sprague Dawley
cinsi erkek siçanlar, ayri kafeslerde ve 12 : 12 saat aydinlik : karanlik kosullarda, istenildigi
kadar yiyecek ve su verilerek tutulmustur. Siçanlara anestezi uygulanmis ve deri altina mini
bir geçisim pompasi implanti takilmistir (Alzet, Cupertino, CA). Pompalar ile günde 75, 300
veya 1200 nmol/kg dozda veya 7 gün tasiyici ile A Bilesigi veya B Bilesigi verilmistir. Bireysel
vücut agirligi ve besin tüketimi günlük olarak ölçülmüstür.
7.ci günde siçanlara anestezi uygulanmis ve boynun sag tarafina atriyal kanül takilmistir. 8.ci
günde iv glikoz tolerans testi yapilmis ve -10 ve 0 zamanlarinda heparinize edilmis siringalar
ile kan örnekleri alinmistir. 0 zamaninda kan örneginin alinmasindan hemen sonra, siçanlara
kalici kanül vasitasi ile glikoz (1 g/kg) enjekte edilmistir. Müteakip kan örnekleri 2.5, 5, 10, 20
ve 40 dakika sonra alinmistir. Glikoz ve (Diagnostic Chemicals Limited) ve insülin (Alpco)
plazma seviyeleri piyasadan temin edilen kitler ile belirlenmistir. Sonuçlar, Sekil 2A ila D ve
Glikoz tolerans testleri
Deney baslamadan önce 12 hafta süre ile normal diyet (30 g; Research Diets 12450) ile veya
fareler ayri kafeslerde ve 12 : 12 saat aydinlik : karanlik kosullarda, istenildigi kadar yiyecek
ve su verilerek muhafaza edilmistir. Farelere anestezi uygulanmis ve deri altina mini bir
geçisim pompasi implanti takilmistir (Alzet, Cupertino, CA). Pompalar ile günde 200, 600
veya 1800 nmol/kg dozda veya 14 gün boyunca tasiyici ile A Bilesigi verilmistir. 14.cü günde
fareler 18 saat süre ile veya gece boyunca aç birakilmistir. 15.ci günde farelere (2 g/kg) ip
glikoz enjekte edilerek glikoz toleransi testi yapilmistir. Glikoz enjeksiyonundan sonra 0, 15,
, 60 ve 180.ci dakikalarda kuyruk çubugu ile kan örnekleri alinmis ve kandaki glikoz
seviyesi Accu-Chek glukometre kullanilarak ölçülmüstür. Sonuçlar Sekil 4 'te
gösterilmektedir.
Erkek, Lep°b/LepOb fareler (50 9) grup halinde 12 : 12 saat aydinlik : karanlik kosullarda,
istenildigi kadar yiyecek ve su verilerek tutulmustur. Fareler, 18 saat süre ile veya gece
boyunca aç birakilmis ve bir ip glikoz tolerans testi yapilmistir. Farelere -15 dakikalarda 6.4
pmol/kg dozda A Bilesigi enjekte edilmis ve kuyruk çubugu ile kan örnegi alinmistir. Farelere
çubuguyla kan örnekleri alinmis ve Glukometre Elite XL (Bayer Corporation) kullanilarak
kandaki glikoz seviyesi ölçülmüstür. Sonuçlar Sekil 5 ”te gösterilmektedir.
Verilis ve Kullanilis
Bu patent hakki bildiriminin peptidleri farmasötik olarak kabul edilebilir tuzlar seklinde
verilebilir. Bu tür tuzlarin örnekleri, organik asitler (örnegin Iaktik, maleik, sitrik, malik,
askorbik, süksinik, benzoik, metansülfonik, toluensülfonik veya pamoik asit), inorganik asitler
(örnegin hidroklorik asit, sülfürik asit veya fosforik asit) ve polimerik asitler (örnegin tannik
asit, karboksimetil selülöz, polilaktik, poliglikolik veya polilaktik-glikolik asit kopolimerleri) ile
olusan tuzlari içerir, ancak bunlar ile sinirli degildir. Mevcut patent hakki bildiriminin peptid
tuzunu yapmanin tipik bir yöntemi teknikte iyi bilinmektedir ve standart tuz alisveris metotlari
ile gerçeklestirilebilir. Buna uygun olarak, mevcut patent hakki bildiriminin TFA peptid tuzu
(TFA tuzu hazirlayici HPLC kullanilarak, tampon çözelti ihtiva eden TFA ile ayristirilarak
peptidin saflastirilmasi sonucunda elde edilir) peptid az miktarda 0.25 N sulu asetik asit
solüsyonda eritilerek asetat tuzu gibi bir baska tuza dönüstürülebilir. Sonuç olarak, elde
edilen çözelti semi-prep HPLC kolona (Zorbax®, 0.5 saat
süre ile 0.1 N amonyum asetat sulu solüsyon; (2) 0.5 saat süre ile 0.25 N asetik asit sulu
solüsyon; ve (3) 4 mI/dakika akis hizinda (A solüsyonu 0.25 N asetik asit sulu solüsyon; B
solüsyonu asetonitriI/su 80:20 içinde 0.25 N asetik asit) dogrusal gradyan (30 dakikanin
üzerinde B solüsyonunun % 20 ila % 100 'ü) ile çözeltiden ayristirilir. Peptid ihtiva eden
fraksiyonlar toplanir ve kuruyana kadar Iiyofilize edilir.
Teknikte uzman kisiler tarafindan iyi bilindigi üzere, peptitlerin melanokortin reseptörü (MC-
R) agonistinin veya antagonistinin aktivitesi ile birlikte bilinen ve potansiyel kullanimlari çesitli
ve çok sayidadir; dolayisi ile agonist etkisine tepki göstermek amaci ile bu patent hakki
bildiriminin bilesiklerinin verilmesi, melanokortinle ayni etkileri gösterebilir ve melanokortin
gibi kullanilir.
Buna göre, mevcut patent hakki bildirimi kapsaminda etken madde olarak farmasötik olarak
kabul edilen tasiyici ile birlikte formül (I) bilesiklerinden asgari birisinden olusan farmasötik
bilesimi içerir.
Bu patent hakki bildiriminin bilesimindeki etken maddenin dozaji degisebilir; bunun ile birlikte,
etken maddenin uygun dozaj formunun elde edilebilecegi miktarda olmasi gerekir. Seçilen
dozaj, verilme seklinde ve tedavi süresinde istenen terapötik etkiye baglidir. Genel olarak, bu
patent hakki bildiriminin aktiviteleri ile ilgili etkili dozaj, tek doz olarak veya birden fazla doza
araligindadir.
Bu patent hakki bildiriminin bilesikleri agizdan, parenteral (örnegin, kas içine, periton içine,
damar içine veya deri altina enjeksiyon veya implant), nazal, vajinal, rektal, dil alti veya topik
yollar ile verilebilir ve her verme yolu için uygun dozaj formlarini saglayan farmasötik olarak
kabul edilebilen tasiyicilar ile formüle edilebilir.
Agizdan verilen kati dozaj formlari kapsülleri, tabletleri, haplari, tozlari ve granülleri içerir. Bu
kati dozaj formlarinda, aktif bilesik sakaroz, Iaktoz veya nisasta gibi farmasötik olarak kabul
edilebilen en az bir etkisiz (inert) tasiyici ile karistirilir. Söz konusu dozaj formlari ayrica,
normal uygulama olarak, söz konusu etkisiz seyrelticiler disinda ilave olarak, örnegin
magnezyum stearat gibi kaydirici maddeleri içerebilir. Kapsüller, tabletler ve haplarda, dozaj
formunda ayni zamanda tampon maddeler de bulunabilir. Tabletler ve haplar ilave olarak
enterik kaplama maddeleri ile hazirlanabilir.
Agizdan verilen sivi dozaj formlari farmasötik olarak kabul edilen emülsiyonlari, çözeltileri,
süspansiyonlari, suruplari, ilgili teknolojide yaygin olarak kullanilan su gibi etkisiz seyrelticileri
içeren iksirleri içerir. Söz konusu etkisiz seyrelticilerin yani sira, bilesim ayrica sulandirici
maddeler, emülsiyonlastirici ve askida tutan maddeler ve tatlandirici, aroma veren ve koku
verici maddeler gibi adjuvanlar (yardimci maddeler) içerebilir.
Bu patent hakki bildirimi uygun olarak parenteral yol ile verilen preparatlar steril sulu veya
susuz çözeltileri, süspansiyonlari veya emülsiyonlari içerir. Susuz çözücü veya tasiyici
maddelere örnek olarak propilen glikol, polietilen glikol, zeytinyagi, misir yagi gibi bitkisel
yaglar, jelatin ve etil oleat gibi enjekte edilebilen organik esterler verilebilir. Söz konusu dozaj
formlari ayrica koruyucu, sulandirici, emülsiyonlastirici ve yayici maddeler gibi adjuvanlari
da içerebilir. Preparatlar, örnegin bakteri tutucu bir filtreyle filtre edilerek, bilesime sterize
edici maddeler ilave ederek, bilesimlere isin uygulayarak veya bilesimleri isitarak sterilize
edilebilir. Preparatlar ayrica kullanilmadan hemen önce steril suda veya enjekte edilebilen bir
baska steril ortamda çözünen steril kati bilesimler seklinde de üretilebilir.
Rektal veya vajinal yol ile verilen bilesimler tercihli bir sekilde, etken maddeye ilave olarak
kakao yagi veya supozituvar (fitil mumu gibi) ilaç katkilarini içeren fitillerdir.
Nazal veya dil alti yol ile verilen bilesimler de teknikte iyi bilinen standart ilaç katkilari ile
hazirlanir.
Ayrica, bu patent hakki bildiriminin bilesigi asagidaki patent ve patent basvurularinda tarif
edilenler gibi yavas salinimli bilesimlerin içinde verilebilir. ABD Patent No. 5,672,659
yayininda yavas salinimli bilesimlerin biyoaktif madde ve polyesterden olustugu
anlatilmaktadir. ABD Patent No. 5,595,760 yayininda yavas salinimli bilesimlerin jellesebilir
sekilde biyoaktif maddeden olustugu anlatilmaktadir. ABD Patent No. 5,821,221 yayininda
yavas salinimli bilesimlerin polimerik yavas salinimli bilesimlerin biyoaktif madde ve
kitosandan olustugu anlatilmaktadir. ABD Patent No. 5,916,883 yayininda yavas salinimli
bilesimlerin biyoaktif madde ve siklodekstrinden olustugu anlatilmaktadir.
DIZI LISTESI
<110> FRANSA BILIMSEL ARASTIRMALAR VE UYGULAMALAR TOPLULUGU
LOUISIANA EYALET ÜNIVERSITESI VE TARIM VE MEKANIK KOLEJI DENETIM
Halem, Heather
Culler, Michael
Butler, Andrew
<120> INSÜLIN DUYARLILIGININ TEDAVISINDE MELANOKORTINLERIN
KULLANIMI
<130> 183P/PCT2
<160> 293
<170> Patent versiyonu 3.5
<210> 1
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-Ala veya 1-amino-i-siklohekzankarboksilik asit (A6c)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDASYON
<400> 1
xaa Asp His xaa Arg Trp xaa Lys
<210> 2
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis NIe
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 6-aminohekzan0ik asit (Ahx) veya 5-aminopentanoik asit (Apn)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDASYON
<400> 2
Xaa Cys His Xaa Arg Trp Xaa Cys
<210> 3
<211> 9
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Phe
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = Ala, beta-Ala veya 4-amin0bütrik asit (Gaba)
<220>
<221> MISC_FEATU RE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MOD_RES
<222>(9›49)
<223> AMIDASYON
<400> 3
Xaa Cys His Xaa Arg Trp Xaa Xaa Thr
<210> 4
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (AC) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 5-aminopentanoik asit (Apn)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDASYON
<400> 4
Xaa Asp His Xaa Arg Trp Xaa Lys
<210> 5
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1 )..(1)
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-aminobütrik asit (Gaba)
<220>
<221> MOD_RES
<222>(8yi8)
<223> AMIDASYON
<400> 5
xaa Asp His Xaa Arg Trp Xaa Lys
<210> 6
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MlSC_FEATURE
<222> (1)..(1)
<223> Xaa = D-beta-(2-naftiII)Ala (D-2-Nal), beta-siklohekzilAla (Cha) veya Nle, tümü
asil Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> SikIIk
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-amin0bütrik asit (Gaba)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDASYON
<400> 6
Xaa Asp His Xaa Arg Trp Xaa Lys
<210> 7
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa =D-Ala, beta-Ala, 4-aminobütrik asit (Gaba), alfa-aminoizobütrik asit (Aib)
veya Gly
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDASYON
<400> 7
Xaa Cys Xaa His Xaa Arg Trp Cys
<210> 8
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (2)..(2)
<223> Xaa = D-Cys
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = Ala,D-Ala, beta-Ala, 4-amin0bütrik asit (Gaba), alfa-aminoizobütrik asit
(Aib) veya Gly
<220>
<221> MlSC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDASYON
<400> 8
xaa Xaa Xaa His Xaa Arg Trp Cys
<210> 9
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa :D-Ala, beta-Ala, 4-aminobütrik asit (Gaba), alfa-aminoizobütrik asit (Aib)
veya Gly
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDASYON
<400> 9
Xaa Cys Xaa His Xaa Arg Trp xaa
<210> 10
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (2)..(2)
<223> Xaa = D-Cys
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = Ala, D-Ala, beta-Ala, 4-aminobütrik asit (Gaba) veya alfa-aminoizobütrik
asit (Aib)
<220>
<221>AMSC_FEATURE
<222>(5yi5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDASYON
<400> 10
Xaa Xaa Xaa His Xaa Arg Trp Xaa
<210> 11
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = oktahidroindol-2-karboksilik asit (Oic), sikloheksilGly (Chg), homo-
sikloheksilAla (hCha), D-Cha,nipekotik asit (Nip), hPro, hLeu, Phe, D-Phe. D-Chg,
hPhe, beta-homoMet, veya 4-amin0bütrik asit (Gaba), tümü asil Ac) ile modifiye
edilmis
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MlSC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-amin0bütrik asit (Gaba)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDASYON
<400> 11
Xaa Asp His Xaa Arg Trp Xaa Lys
<210> 12
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = beta-sikloheksilAla (Cha) n-bütanoil ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-amin0bütrik asit (Gaba)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDASYON
<400> 12
Xaa Asp His Xaa Arg Trp Xaa Lys
<210> 13
<211>8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = homo-sikloheksilAla (hCha), Leu, homo-Leu (hLeu) veya Phe, tümü asil
Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MlSC_FEATURE
<222> (6)..(6)
<223> Xaa = D-Trp
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDASYON
<400> 13
xaa Asp His Xaa Arg xaa Ala Lys
<210> 14
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MlSC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = D-Trp
<220>
<221>RMSC_FEATURE
<222>(7yi7)
<223> Xaa = D-Ala, beta-Ala, 4-aminobütrikasit (Gaba), 7-amin0heptanoik asit (Aha)
veya 5-amin0pentanoik asit (Apn)
<220>
<221> MOD_RES
<222>(8)(8)
<223> AMIDASYON
<400> 14
<210> 15
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222>(1yi1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = D-Trp
<220>
<221>RMSC_FEATURE
<222>(7yi7)
Xaa Asp His Xaa Arg Xaa Xaa Lys
<223> Xaa = 5-aminopentanoik asit (Apn), 4-aminobütrik asit (Gaba), 6-
aminohekzanoik asit (Ahx), beta-Ala, veya D-Ala
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDASYON
<400> 15
Xaa Cys His Xaa Arg Xaa Xaa Cys
<210> 16
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MlSC_FEATURE
<222> (5)..(5)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = Trp, beta-(2-naftil)Ala (2-Nal) veya beta-(1-naftil)Ala (1-Nal)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDASYON
<400> 16
Xaa Cys Xaa His Xaa Arg Xaa Cys
<210> 17
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = N-bütanoil ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-(2-naftiI)AIa (2-Nal) veya Trp
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDASYON
<400> 17
Xaa Cys Xaa His Xaa Arg Xaa Cys
<210> 18
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-(2-naftiI)AIa (2-Nal), beta-(1-naftil)AIa (1-Nal) veya 3-benzotienilAla
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDASYON
<400> 18
Xaa Cys Xaa His Xaa Arg Xaa Cys
<210> 19
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MlSC_FEATURE
<222> (7)..(7)
<223> Xaa = D-Ala
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDASYON
<400> 19
Xaa Asp His Xaa Arg Trp Xaa Lys
<210> 20
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-beta-Z-naftiIAla (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 3-benzotienilAla (Bal)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDASYON
<400> 20
Xaa Cys Xaa His Xaa Arg Xaa Cys
<210> 21
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (2)..(2)
<220>
<221> MlSC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDASYON
<400> 21
Xaa Xaa Xaa His Xaa Arg Trp Cys
<210> 22
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis NIe
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (2)..(2)
<223> Xaa = Cys veya penisillamin (Pen)
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MlSC_FEATURE
<222> (8)..(8)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDASYON
<400> 22
xaa xaa xaa His xaa Arg Trp xaa
<210> 23
<211> 9
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MlSC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Phe
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MlSC_FEATU RE
<222> (5)..(5)
<223> Xaa = homo-Arg (hArg)
<220>
<221> MlSC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-Ala
<220>
<221> MlSC_FEATURE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MOD_RES
<222> (9)..(9)
<223> AMIDASYON
<400> 23
Xaa Cys His Xaa Xaa Trp Xaa Xaa 'rhr
<210> 24
<211> 9
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Phe
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-(Et)Tyr
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = Arg veya homo-Arg (hArg)
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MOD_RES
<222> (9)..(9)
<223> AMIDASYON
<400> 24
Xaa Cys His Xaa Xaa Trp Xaa Xaa Thr
<210> 25
<211> 9
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Phe
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MOD_RES
<222> (9)..(9)
<223> AMIDASYON
<400> 25
Xaa Cys His Xaa Arg Xaa Xaa Xaa Thr
<210> 26
<211> 9
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Phe
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe veya D-(Et)Tyr
<220>
<221> MlSC_FEATURE
<222> (5)..(5)
<223> Xaa = homo-Arg (hArg)
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MOD_RES
<222> (9)..(9)
<223> AMIDASYON
<400> 26
Xaa Cys His Xaa Xaa Xaa Xaa Xaa Thr
<210> 27
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MlSC_FEATURE
<222> (7)..(7)
<223> Xaa = 5-aminopentanoik asit (Apn)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDASYON
<400> 27
Xaa Cys His Xaa Arg Trp Xaa Cys
<210> 28
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = Trp veya 3-benzotieniIAla (Bal)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDASYON
<400> 28
Xaa Asp Xaa His Xaa Arg Xaa Lys
<210> 29
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MlSC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = penisillamin (Pen) veya Cys
<220>
<221> MOD_RES
<222> (8)..(8)
<223> C-terminus serbest asittir
<400> 29
Xaa Cys Xaa His Xaa Arg Trp Xaa
<210> 30
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-alfa-aminobütrik asit (D-Abu), D-Val, D-lle, D-Leu, D-tert-Leu (D-Tle)
veya D-beta-sikloheksilAla (D-Cha)
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDASYON
<400> 30
Xaa Cys Xaa His Xaa Arg Trp Cys
<210> 31
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (2)..(2)
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-aminobütrik asit (Gaba)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDASYON
<400> 31
Xaa Xaa His Xaa Arg Trp Xaa Cys
<210> 32
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (2)..(2)
<223> Xaa = Cys veya penisillamin (Pen)
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MlSC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-aminobütrik asit (Gaba)
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<220>
<221> MOD_RES
<222>(8lls)
<223> AMIDASYON
<400> 32
Xaa Xaa His Xaa Arg Trp Xaa Xaa
<210> 33
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MlSC_FEATURE
<222> (1)..(1)
<223> Xaa = Leu, beta-sikloheksilAla (Cha). Ile, Phe, Val veya beta-(2-naftil)AIa (2-
Nal), tümü asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-amin0bütrik asit (Gaba)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDASYON
<400> 33
Xaa Cys His Xaa Arg Trp Xaa Cys
<210> 34
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle veya Phe
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-aminobütrik asit (Gaba)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDASYON
<400> 34
Xaa Cys His Xaa Arg Trp Xaa Cys
<210> 35
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis NIe
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = beta-(3-piridi|)Ala (3-Pal)
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-aminobütrik asit (Gaba)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDASYON
<400> 35
Xaa Cys Xaa Xaa Arg Trp Xaa Cys
<210> 36
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MlSC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MOD_RES
<222> (8)..(8)
<223> C-terminus serbest asittir
<400> 36
Xaa Cys Xaa His Xaa Arg Trp Cys
<210> 37
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (AC) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = D-Trp
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-amin0bütrik asit (Gaba)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDASYON
<400> 37
Xaa Cys His Phe Arg Xaa Xaa Cys
<210> 38
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)AIa (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = Ala veya beta-Ala
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDASYON
<400> 38
Xaa Asp His Xaa Arg Trp Xaa Lys
<210> 39
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221>ETKIALANI
<222>(2y48)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-amin0bütrik asit (Gaba) veya 6-aminohekzan0ik asit (Ahx)
<220>
<221> MOD_RES
<222>(8ll8)
<223> AMIDASYON
<400> 39
Xaa Cys His Xaa Arg Trp Xaa Cys
<210> 40
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATU RE
<222> (1)..(1)
<223> Xaa = homo-Phe (hPhe) veya beta-sikloheksilAla (Cha), her ikisi de asil (Ac)
ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MlSC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-aminobütrik asit (Gaba)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDASYON
<400> 40
Xaa Asp His Xaa Arg Trp Xaa Lys
<210> 41
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MlSC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-Ala veya 5-aminopentan0ik asit (Apn)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> C-terminus serbest asittir
<400> 41
Xaa Asp His Xaa Arg Trp Xaa Lys
<210> 42
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MlSC_FEATURE
<222> (7)..(7)
<223> Xaa = 6-amin0hekzanoik asit (Ahx) veya 5-aminopentan0ik asit (Apn)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> C-terminus serbest asittir
<400> 42
xaa Cys His Xaa Arg Trp Xaa Cys
<210> 43
<211> 9
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MlSC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Phe
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MlSC_FEATU RE
<222> (7)..(7)
<223> Xaa = Ala, beta-Ala veya 4-amin0bütrik asit (Gaba)
<220>
<221> MlSC_FEATURE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MOD_RES
<222> (9)..(9)
<223> C-terminus serbest asittir
<400> 43
Xaa Cys His Xaa Arg Trp Xaa Xaa Thr
<210> 44
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<, D-Cha, homo-
sikloheksilAla (hCha), D-Chg veya homo-Phe (hPhe), tümü asil (Ac) ile modifiye
edilmis
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-amin0bütrik asit (Gaba)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> C-terminus serbest asittir
<400> 44
Xaa Asp His Xaa Arg Trp Xaa Lys
<210> 45
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = D-Trp
<220>
<221> MlSC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-aminobütrik asit (Gaba), 6-aminohekzanoik asit (Ahx), beta-Ala veya
<220>
<221> MOD_RES
<222> (8)..(8)
<223> C-terminus serbest asittir
<400> 45
xaa Cys His Xaa Arg Xaa Xaa Cys
<210> 46
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü ligandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222>(7ylî)
<223> Xaa =Trp, beta-(2-naftil)Ala (2-Nal), beta-(1-naftil)Ala (1-Nal) veya 3-
benzotienilalanin (Bal)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> C-terminus serbest asittir
<400> 46
Xaa Cys Xaa His Xaa Arg Xaa Cys
<210> 47
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221>RMSC_FEATURE
<222>(1ll1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222>(2yls)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (2)..(2)
<220>
<221> MlSC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MOD_RES
<222> (8)..(8)
<223> C-terminus serbest asittir
<400> 47
Xaa Xaa Xaa His Xaa Arg Trp Cys
<210> 48
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis NIe
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-aminobütrik asit (Gaba)
<220>
<221> MlSC_FEATURE
<222> (8)..(8)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> C-terminus serbest asittir
<400> 48
xaa Cys His xaa Arg Trp Xaa xaa
<210> 49
<211>8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (AC) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222>(5ll5)
<223> Xaa = D-beta-(2-naftiI)Ala (D-2-Nal)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDASYON
<400> 49
Arg Cys Xaa His Xaa Arg Trp Cys
<210> 50
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Arg veya D-Arg, her ikisi de asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MlSC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDASYON
<400> 50
Xaa Cys Xaa His Xaa Arg Trp Cys
<210> 51
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Arg veya Arg, her ikisi de asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDASYON
<400> 51
Xaa Cys Xaa His Xaa Arg Trp Xaa
<210> 52
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Arg veya Arg, her ikisi de asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MlSC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-amin0bütrik asit (Gaba)
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDASYON
<400> 52
Xaa Cys His Xaa Arg Trp Xaa Xaa
<210> 53
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Arg veya Arg, her ikisi de asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDASYON
<400> 53
Xaa Asp His Xaa Arg Trp Ala Lys
<210> 54
<211> 9
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MlSC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(9)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MlSC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = Gly, D-Ala, beta-Ala, 4-aminobütrik asit (Gaba) veya 5-aminopentan0ik
asit (Apn)
<220>
<221> MOD_RES
<222> (9)..(9)
<223> AMIDASYON
<400> 54
Xaa Cys Xaa His Xaa Arg Trp Xaa Cys
<210> 55
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222>(6ylö)
<223> Xaa = Trp veya beta-(2-naftil)alanin (2-Nal)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDASYON
<400>55
Cys Glu His Xaa Arg Xaa Ala Cys
<210> 56
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (2)..(2)
<223> Xaa = D-Ala
<220>
<221> MlSC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = Trp veya beta-(2-naftil)Ala (2-Nal)
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDASYON
<400> 56
Cys Xaa His Xaa Arg Xaa Ala Cys
<210> 57
<211> 9
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis NIe
<220>
<221> ETKI ALANI
<222> (2)..(9)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = Ala, beta-Ala veya 4-amin0bütrik asit (Gaba)
<220>
<221> MOD_RES
<222> (9)..(9)
<223> AMIDASYON
<400> 57
Xaa Cys Xaa His Xaa Arg Trp Xaa Cys
<210> 58
<211> 9
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(9)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATU RE
<222> (7)..(7)
<223> Xaa = 3-benzotienilAla (Bal)
<220>
<221> MOD_RES
<222> (9)..(9)
<223> AMIDASYON
<400> 58
Xaa Asp Xaa His Xaa Arg Xaa Ala Lys
<210> 59
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Glu
<220>
<221> MlSC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDASYON
<400> 59
Xaa Cys Xaa His Xaa Arg Trp Cys
<210> 60
<211> 18
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (12)..(12)
<223> Xaa = Nle
<220>
<221> ETKI ALANI
<222> (13)..(18)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (15)..(15)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MOD_RES
<222> (18)..(18)
<223> AMIDASYON
<400> 60
<210> 61
<211> 19
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (12)..(12)
<223> Xaa = 8-amino-3,6-di0ksaoktanoik asit (Doc)
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = Nle
<220>
<221> ETKI ALANI
<222> (14)..(19)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (16)..(16)
<223> Xaa = D-beta-(2-naftiI)Ala (D-2-Nal)
<220>
<221> MOD_RES
<222>(19)(19)
<223> AMIDASYON
<400> 61
<210> 62
<211> 19
<212> PRT
<213> Yapay Dizi
Tyr Gly Arg Lys Lys Arg Arg Gln Arg Arg Arg Xaa Asp His Xaa Arq
Tyr Giy Arg Lys Lys Arg Arg Gln Arg Arg Arg Xaa Xaa Asp His Xaa
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle veya Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(7)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (19)..(19)
<223> AMIDASYON
<400> 62
Xaa Asp His Xaa Arg Trp Lys Xaa Tyr Giy Arg Lys Lys Arg Arg Gin
1 5 10 15
<210> 63
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle
<220>
<221> ETKI ALANI
<222> (2)..(7)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (8)..(9)
<223> Xaa = 8-amin0-3,6-dioksa0ktanoik asit (Doc)
<220>
<221> MOD_RES
<222>(20y420)
<223> AMIDASYON
<400> 63
Xaa Asp His Xaa Arg Trp Lys Xaa Xaa Tyr Gly Arg Lys Lys Arg Arg
l 5 10 15
Gln Arg Arg Arg<210> 64
<211> 22
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigaridi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis NIe
<220>
<221> ETKI ALANI
<222> (2)..(7)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MOD_RES
<222> (22)..(22)
<223> AMIDASYON
<400> 64
Xaa Asp His Xaa Arg Trp Lys Pro Pro Lys Asp Tyr Gly Arg Lys Lys
1 5 10 15
<211> 23
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)AIa (D-2-Nal)
<220>
<221> MOD_RES
<222> (23)..(23)
<223> AMIDASYON
<400> 65
Cys Glu His xaa Arg Trp Giy Cys Pro Pro Lys Asp Tyr Gly Arg Lys
l 5 10 15
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221› ETKI ALANI
<222> (2)..(7)
<223> Siklik
<220>
<221› MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftiI)AIa (D-2-Nal)
<220>
<221› MlSC_FEATURE
<222> (8)..(9)
<223> Xaa = beta-Ala
<220>
<221› MOD_RES
<222> (20)..(20)
<223> AMIDASYON
<400> 66
Xaa Asp His Xaa Arg Trp Lys Xaa Xaa Tyr Giy Arg Lys Lys Arg Arg
1 5 10 15
<210> 67
<211> 23
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221› MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (AC) ile modifiye edilmis Nle
<220>
<221› ETKI ALANI
<222> (2)..(7)
<223> Siklik
<220>
<221› MISC_FEATU RE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (12)..(12)
<223> Xaa = 8-amin0-3,6-di0ksa0ktanoik asit (Doc)
<220>
<221> MOD_RES
<222> (23)..(23)
<223> AMIDASYON
<400> 67
Xaa Asp His Xaa Arg Trp Lys Pro Pro Lys Asp Xaa Tyr Gly Arg Lys
1 5 10 15
<211> 24
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> MISC_FEATU RE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)AIa (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = 8-amino-3,6-di0ksaoktan0ik asit (Doc)
<220>
<221> MOD_RES
<222> (24)..(24)
<223> AMIDASYON
<400> 68
Cys Glu His Xaa Arg Trp Giy Cys Pro Pro Lys Asp Xaa Tyr Giy Arg
1 5 10 15
<211> 24
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221>ETKIALANI
<222>(1y48)
<223> Siklik
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)AIa (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala veya 8-amino-3,ö-dioksaoktanoik asit (Doc)
<220>
<221> MOD_RES
<222>(24yl24)
<223> AMIDASYON
<400> 69
Cys Glu His Xaa Arg Trp Ala Cys Pro Pro Lys Asp Xaa Tyr Gly Arg
1 5 10 15
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(7)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (8)..(9)
<223> Xaa = 8-amin0-3,6-dioksaoktanoik asit (Doc)
<220>
<221> MOD_RES
<222> (20)..(20)
<223> AMIDASYON
<400> 70
Xaa Asp His Xaa Arg Trp Lys Xaa Xaa Tyr Giy Arg Lys Lys Arg Arg
J. 5 10 15
Gln Arg Arg Arg<210> 71
<211> 24
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (AC) ile modifiye edilmis
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = beta-(2-naftiI)AIa (2-Nal), beta-(1-naftiI)AIa (1-Nal) veya 3-benzotienilAIa
<220>
<221> MlSC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (24)..(24)
<223> AMIDASYON
<400> 71
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Tyr Gly Arg
<211> 22
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (AC) ile modifiye edilmis
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (22)..(22)
<223> AMIDASYON
<400> 72
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Arg Arg Arg
<211> 23
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigaridi
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = beta-2-naftilAla (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<220>
<221> MISC_FEATU RE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (23)..(23)
<223> AMIDASYON
<400> 73
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp xaa Giy Arg Arg
<211> 24
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = 3-benzotienilAla (Bal)
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (24)..(24)
<223> AMIDASYON
<400> 74
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Tyr Gly Arg
1 5 10 15
<211> 24
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (24)..(24)
<223> AMIDASYON
<400> 75
Cys Glu His Xaa Arg Trp Ala Cys Pro Pro Lys Asp Xaa Tyr Gly Arg
1 5 10 15
<210> 76
<211> 24
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> MISC_FEATU RE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (24)..(24)
<223> AMIDASYON
<400> 76
Cys Glu His Xaa Arg Trp Ala Cys Pro Pro Lys Asp Xaa Tyr Giy Arg
1 5 10 15
<211> 24
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MlSC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (24)..(24)
<223> AMIDASYON
<400> 77
Cys Glu His Xaa Arg Trp Ala Cys Pro Pro Lys Asp Xaa Tyr Gly Arg
1 5 10 15
<211> 24
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> MISC_FEATU RE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (24)..(24)
<223> AMIDASYON
<400> 78
Cys Glu His Xaa Arg Trp Ala Cys Pro Pro Lys Asp Xaa Tyr Gly Arg
<210> 79
<211> 24
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftiI)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (15)..(15)
<223> Xaa = alfa-aminoizobütrik asit (Aib)
<220>
<221> MOD_RES
<222> (24)..(24)
<223> AMIDASYON
400> 79
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Tyr Xaa Arg
1 5 10 15
<211> 22
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> MISC_FEATU RE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)AIa (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = beta-(1-naftiI)AIa (1-Nal)
<220>
<221> MISC_FEATURE
<222> (11)..(11)
<223> Xaa = Arg veya Lys
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (22)..(22)
<223> AMIDASYON
<400> 80
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Xaa Asp Xaa Arg Arg Arg
1 5 10 15
<211> 23
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> MISC_FEATU RE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)AIa (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Beta-(1-naftiI)AIa (1-Nal) veya beta-(2-naftiI)AIa (2-Nal)
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (23)..(23)
<223> AMIDASYON
<400> 81
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Arg Arg Arg
<211> 22
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü ligandi
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)AIa (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = beta-(2-naftil)Ala (2-Nal)
<220>
<221> MISC_FEATURE
<222> (11)..(11)
<223> Xaa = Arg veya Lys
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (22)..(22)
<223> AMIDASYON
<400> 82
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Xaa Asp Xaa Arg Arg Arg
<211> 23
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (AC) ile modifiye edilmis
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(Z-naftiI)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = 3-benzotienilAla (Bal)
<220>
<221> MISC_FEATURE
<222> (11)..(11)
<223> Xaa = Arg veya Lys
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (23)..(23)
<223> AMIDASYON
<400> 83
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Xaa Asp Xaa Arg Arg Arg
<211> 22
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (AC) ile modifiye edilmis
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(Z-naftiI)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = 3-benzotienilAla (Bal)
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (22)..(22)
<223> AMIDASYON
<400> 84
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Arg Asp Xaa Arg Arg Arg
1 5 10 15
<211> 24
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221>ETKIALANI
<222>(1y48)
<223> Siklik
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)AIa (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222>(24yl24)
<223> AMIDASYON
<400> 85
Cys Glu His Xaa Arg Trp Ala Cys Pro Pro Lys Asp Xaa Tyr Gly Arg
1 5 10 15
<211> 24
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> MlSC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (24)..(24)
<223> AMIDASYON
<400> 86
Cys Glu His Xaa Arg Trp Ala Cys Pro Pro Lys Asp Xaa Tyr Giy Arg
1 5 10 15
<211> 24
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222>(24y424)
<223> AMIDASYON
<400> 87
Cys Giu His Xaa Arg Trp Ala Cys Pro Pro Lys Asp Xaa Tyr Gly Arg
1 5 10 15
<211> 22
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü ligandi
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATU RE
<222> (6)..(6)
<223> Beta-(1-naftil)Ala (1-Nal) veya beta-(2-naftiI)Ala (2-Nal)
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (22)..(22)
<223> AMIDASYON
<400> 88
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Arg Arg Lys
<211> 22
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> MISC_FEATU RE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)AIa (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = beta-(1-naftiI)AIa (1-Nal)
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (22)..(22)
<223> AMIDASYON
<400> 89
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Arg Lys Arg
<211> 24
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (AC) ile modifiye edilmis
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(Z-naftiI)Ala (D-2-Nal)
<220>
<221> MISC_FEATU RE
<222> (6)..(6)
<223> Xaa = beta-(2-naftiI)AIa (2-Nal)
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (24)..(24)
<223> AMIDASYON
<400> 90
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Tyr Gly Arg
1 5 10 15
<210> 91
<211> 23
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftiI)AIa (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = beta-(2-naftiI)AIa (2-Nal)
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (23)..(23)
<223> AMIDASYON
<400> 91
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Gly Arg Arg
1 5 10 15
Lys Arg Arg Gln Arg Arg Arg10
<210> 92
<211> 23
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATU RE
<222> (6)..(6)
<223> Xaa = beta-(2-naftil)AIa (2-Nal) veya beta-(1-naftiI)AIa (1-Nal)
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (23)..(23)
<223> AMIDASYON
<400> 92
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Gly Arg Lys
1 5 10 15
<211> 22
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = beta-(1-naftiI)AIa (1-Nal)
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (22)..(22)
<223> AMIDASYON
<400> 93
Cys Glu His Xaa Arg xaa Ala Cys Pro Pro Lys Asp xaa Arg Arg Lys
1 5 10 15
<211> 22
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MlSC_FEATURE
<222> (6)..(6)
<223> Xaa = beta-(1-naftil)Ala (1-Nal)
<220>
<221> MlSC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (22)..(22)
<223> AMIDASYON
<400> 94
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Arg Lys Arg
1 5 10 15
<211> 24
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(8)
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = beta-(1-naftiI)AIa (1-Nal)
<220>
<221> MlSC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (24)..(24)
<223> AMIDASYON
<400> 95
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Tyr Gly Arg
1 5 10 15
<211> 24
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = beta-(1-naftil)Ala (1-Nal)
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222>(24y424)
<223> AMIDASYON
<400> 96
Cys Giu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Tyr Gly Arg
1 5 10 15
<211> 23
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü ligaridi
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATU RE
<222> (6)..(6)
<223> Xaa = beta-(1-naftiI)Ala (1-Nal)
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (23)..(23)
<223> AMIDASYON
<400> 97
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Giy Arg Arg
<211> 22
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> MISC_FEATU RE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)AIa (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = beta-(2-naftiI)AIa (2-Nal)
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (22)..(22)
<223> AMIDASYON
<400> 98
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Arg Arg Lys
<211> 22
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(Z-naftiI)Ala (D-2-Nal)
<220>
<221> MISC_FEATU RE
<222> (6)..(6)
<223> Xaa = beta-(2-naftiI)AIa (2-Nal)
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (22)..(22)
<223> AMIDASYON
<400> 99
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Arg Lys Arg
1 5 10 15
<210> 100
<211> 24
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftiI)AIa (D-2-Nal)
<220>
<221> MISC_FEATU RE
<222> (6)..(6)
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (24)..(24)
<223> AMIDASYON
<400> 100
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Tyr Gly Arg
1 5 10 15
<210> 101
<211> 24
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATU RE
<222> (6)..(6)
<223> Xaa = beta-(2-naftil)AIa (2-Nal) veya 3-benzotienilAIa (Bal)
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (24)..(24)
<223> AMIDASYON
<400> 101
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Tyr Gly Arg
1 5 10 15
<211> 23
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (23)..(23)
<223> AMIDASYON
<400> 102
Cys Glu His xaa Arg Xaa Ala Cys Pro Pro Lys Asp xaa Gly Arg Arg
1 5 10 15
<211> 23
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MlSC_FEATURE
<222> (6)..(6)
<223> Xaa = beta-(2-naftil)AIa (2-Nal) veya 3-benzotienilAla (Bal)
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (23)..(23)
<223> AMIDASYON
<400> 103
Cys Giu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Gly Arg Lys
1 5 10 15
<211> 22
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<220>
<221> MlSC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (22)..(22)
<223> AMIDASYON
<400> 104
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Arg Arg Lys
<211> 22
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MISC_FEATU RE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222>(22y422)
<223> AMIDASYON
<400> 105
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp Xaa Arg Lys Arg
<210> 106
<211> 24
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigaridi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (24)..(24)
<223> AMIDASYON
<400> 106
Cys Glu His Xaa Arg Trp Ala Cys Pro Pro Lys Asp xaa Tyr Gly Arg
1 5 10 15
<211> 24
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(Z-naftiI)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (24)..(24)
<223> AMIDASYON
<400> 107
Cys Glu His Xaa Arg Trp Ala Cys Pro Pro Lys Asp Xaa Tyr Gly Arg
1 5 10 15
<210> 108
<211> 24
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftiI)AIa (D-2-Nal)
<220>
<221> MlSC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (24)..(24)
<223> AMIDASYON
<400> 108
Cys Glu His Xaa Arg Trp Ala Cys Pro Pro Lys Asp Xaa 'I'yr Gly An;
1 5 10 15
<211> 24
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftiI)AIa (D-2-Nal)
<220>
<221> MlSC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (24)..(24)
<223> AMIDASYON
<400> 109
Cys Glu His Xaa Arg Trp Ala Cys Pro Pro Lys Asp Xaa Tyr Gly Arg
1 5 10 15
<211> 24
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MISC_FEATU RE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (24)..(24)
<223> AMIDASYON
<400> 110
Cys Glu His Xaa Arg Trp Ala Cys Pro Pro Lys Asp Xaa Tyr Gly Arg
<210> 111
<211> 24
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (AC) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MISC_FEATU RE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)AIa (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (24)..(24)
<223> AMIDASYON
<400> 111
Cys Glu His Xaa Arg Trp Ala Cys Pro Pro Lys Asp Xaa Tyr Gly Arg
1 5 10 15
<211> 24
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222>(1)(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)AIa (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (24)..(24)
<223> AMIDASYON
<400> 112
Cys Glu His Xaa Arg Trp Ala Cys Pro Pro Lys Asp Xaa Tyr Gly Arg
1 5 10 15
<211> 22
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (11)..(11)
<223> Xaa = Lys veya Arg
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (22)..(22)
<223> AMIDASYON
<400> 113
Cys Glu His Xaa Arg Trp Ala Cys Pro Pro Xaa Asp Xaa Arg Arg Arg
1 5 10 15
<211> 24
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (AC) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MlSC_FEATURE
<222> (11)..(11)
<223> Xaa = Lys veya Arg
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (24)..(24)
<223> AMIDASYON
<400> 114
Cys Glu His Xaa Arg Trp Ala Cys Pro Pro Xaa Asp Xaa Tyr Gly Arg
1 5 10 15
<211> 23
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (11)..(11)
<223> Xaa = Lys veya Arg
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (23)..(23)
<223> AMIDASYON
<400> 115
Cys Glu His Xaa Arg Trp Ala Cys Pro Pro Xaa Asp Xaa Arg Arg Arg
1 5 10 15
<211> 25
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(Z-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATU RE
<222> (11)..(11)
<223> Xaa = Lys veya Arg
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (25)..(25)
<223> AMIDASYON
<400> 116
Cys Glu His Xaa Arg Trp Ala Cys Pro Pro Xaa Asp Xaa Tyr Giy Arg
1 5 10 15
<210> 117
<211> 22
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = beta-(1-naftiI)AIa (1-Nal)
<220>
<221> MISC_FEATU RE
<222> (11)..(11)
<223> Xaa = Lys veya Arg
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (22)..(22)
<223> AMIDASYON
<400> 117
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Xaa Asp Xaa Arg Arg Arg
<211> 23
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = beta-(1-naftiI)AIa (1-Nal)
<220>
<221> MISC_FEATU RE
<222> (11)..(11)
<223> Xaa = Lys veya Arg
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (23)..(23)
<223> AMIDASYON
<400> 118
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Xaa Asp Xaa Arg Arg Arg
<211> 23
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = beta-(1-naftiI)AIa (1-Nal)
<220>
<221> MISC_FEATU RE
<222> (11)..(11)
<223> Xaa = Lys veya Arg
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (23)..(23)
<223> AMIDASYON
<400> 119
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Xaa Asp Xaa Arg Arg Arg
<211> 24
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> Asil ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = beta-(1-naftiI)AIa (1-Nal)
<220>
<221> MISC_FEATU RE
<222> (11)..(11)
<223> Xaa = Lys veya Arg
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (24)..(24)
<223> AMIDASYON
<400> 120
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Xaa Asp Xaa Tyr Giy Arg
<211> 25
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = beta-(1-naftiI)AIa (1-Nal)
<220>
<221> MISC_FEATU RE
<222> (11)..(11)
<223> Xaa = Lys veya Arg
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (25)..(25)
<223> AMIDASYON
<400> 121
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Xaa Asp Xaa Tyr Giy Arg
1 5 10 15
<210> 122
<211> 25
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = beta-(1-naftiI)AIa (1-Nal)
<220>
<221> MISC_FEATU RE
<222> (11)..(11)
<223> Xaa = Lys veya Arg
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (25)..(25)
<223> AMIDASYON
<400> 122
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Xaa Asp Xaa Tyr Giy Arg
1 5 10 15
<210> 123
<211> 22
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = beta-(2-naftiI)AIa (2-Nal)
<220>
<221> MISC_FEATU RE
<222> (11)..(11)
<223> Xaa = Lys veya Arg
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (22)..(22)
<223> AMIDASYON
<400> 123
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Xaa Asp Xaa Arg Arg Arg
<211> 23
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = beta-(2-naftiI)AIa (2-Nal)
<220>
<221> MISC_FEATU RE
<222> (11)..(11)
<223> Xaa = Lys veya Arg
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (23)..(23)
<223> AMIDASYON
<400> 124
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Xaa Asp Xaa Arg Arg Arg
<211> 23
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = beta-(2-naftiI)AIa (2-Nal)
<220>
<221> MISC_FEATU RE
<222> (11)..(11)
<223> Xaa = Lys veya Arg
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (23)..(23)
<223> AMIDASYON
<400> 125
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Xaa Asp Xaa Arg Arg Arg
<211> 24
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = beta-(2-naftiI)AIa (2-Nal)
<220>
<221> MISC_FEATU RE
<222> (11)..(11)
<223> Xaa = Lys veya Arg
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (24)..(24)
<223> AMIDASYON
<400> 126
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Xaa Asp Xaa Tyr Giy Arg
<211> 25
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = beta-(2-naftiI)AIa (2-Nal)
<220>
<221> MISC_FEATU RE
<222> (11)..(11)
<223> Xaa = Lys veya Arg
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (25)..(25)
<223> AMIDASYON
<400> 127
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Xaa Asp Xaa Tyr Giy Arg
1 5 10 15
<210> 128
<211> 25
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = beta-(2-naftiI)AIa (2-Nal)
<220>
<221> MISC_FEATU RE
<222> (11)..(11)
<223> Xaa = Lys veya Arg
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (25)..(25)
<223> AMIDASYON
<400> 128
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Xaa Asp Xaa Tyr Giy Arg
1 5 10 15
<210> 129
<211> 22
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = 3-benzotienilAIa (Bal)
<220>
<221> MISC_FEATU RE
<222> (11)..(11)
<223> Xaa = Lys veya Arg
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (22)..(22)
<223> AMIDASYON
<400> 129
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Xaa Asp Xaa Arg Arg Arg
<211> 23
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = 3-benzotienilAIa (Bal)
<220>
<221> MISC_FEATU RE
<222> (11)..(11)
<223> Xaa = Lys veya Arg
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (23)..(23)
<223> AMIDASYON
<400> 130
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Xaa Asp Xaa Arg Arg Arg
<211> 23
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = 3-benzotienilAIa (Bal)
<220>
<221> MISC_FEATU RE
<222> (11)..(11)
<223> Xaa = Lys veya Arg
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (23)..(23)
<223> AMIDASYON
<400> 131
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Xaa Asp Xaa Arg Arg Arg
<211> 23
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = 3-benzotienilAIa (Bal)
<220>
<221> MISC_FEATU RE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (23)..(23)
<223> AMIDASYON
<400> 132
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Lys Asp xaa Giy Arg Arg
<211> 24
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATU RE
<222> (6)..(6)
<223> Xaa = 3-benzotienilAla (Bal)
<220>
<221> MISC_FEATURE
<222> (11)..(11)
<223> Xaa = Lys veya Arg
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (24)..(24)
<223> AMIDASYON
<400> 133
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Xaa Asp Xaa 'I'yr Gly Arg
<211> 25
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(Z-naftiI)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = 3-benzotienilAla (Bal)
<220>
<221> MISC_FEATURE
<222> (11)..(11)
<223> Xaa = Lys veya Arg
<220>
<221> MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221› MOD_RES
<222> (25)..(25)
<223> AMIDASYON
<400> 134
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Xaa Asp Xaa Tyr Gly Arg
1 5 10 15
<210> 135
<211> 25
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221› ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221› MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221› MISC_FEATURE
<222> (6)..(6)
<220>
<221› MlSC_FEATURE
<222> (11)..(11)
<223> Xaa = Lys veya Arg
<220>
<221› MISC_FEATURE
<222> (13)..(13)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (25)..(25)
<223> AMIDASYON
<400> 135
Cys Glu His Xaa Arg Xaa Ala Cys Pro Pro Xaa Asp Xaa Tyr Gly Arg
1 5 10 15
<210> 136
<211> 21
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = 8-amin0-3,6-di0ksaoktanoik asit (Doc)
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = 8-amino-3,6-di0ksaoktan0ik asit (Doc) veya bulunmayan
<220>
<221> MOD_RES
<222>(21yl21)
<223> AMIDASYON
<400> 136
Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Tyr Gly Arg Lys Lys Arg
1 5 10 15
<210> 137
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (20)..(20)
<223> AMIDASYON
<400> 137
Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Tyr Gly Arg Lys Lys Arg Gln
1 5 10 15
<211> 19
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221› MlSC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222>(2)(8)
<223> Siklik
<220>
<221› MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221› MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221› MISC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221› MISC_FEATURE
<222> (10)..(10)
<223> Xaa = Gly veya bulunmayan
<220>
<221› MOD_RES
<222> (19)..(19)
<223> AMIDASYON
<400> 138
Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Arg Arg Arg Arg Arg Gln
<210> 139
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis NIe
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MlSC_FEATURE
<222> (10)..(10)
<223> Xaa = Tyr veya bulunmayan
<220>
<221> MOD_RES
<222> (20)..(20)
<223> AMIDASYON
<400> 139
Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Gly Arg Arg Arg Arg Arg
Sin Arg Arg Arg<210> 140
<211> 20
<212> PRT
213› Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MlSC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222>(2)(8)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MlSC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MlSC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (20)..(20)
<223> AMIDASYON
<400> 140
Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Gly Arg Arg Arg Arg Arg Gln
<210> 141
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MlSC_FEATU RE
<222> (1)..
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..
<223> Xaa = D-Ala
<220>
<221> MISC_FEATU RE
<222> (5)..
<223> Xaa = D-Phe
<220>
<221> MISC_FEATU RE
<222> (9)..
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = Tyr veya bulunmayan
<220>
<221> MOD_RES
<222> (20)..(20)
<223> AMIDASYON
<400> 141
Xaa Cys Xaa His Xaa Arg 'I'rp Cys Xaa Xaa Gly Arg Arg Lys Arg Arg
J. 5 10 15
Gln Arg Arg Arg10
<210> 142
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MlSC_FEATU RE
<222> (1)..
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222>(2y.
<223> Siklik
<220>
<221> MISC_FEATU RE
<222>(3y.
<223> Xaa = D-Ala
<220>
<221> MISC_FEATU RE
<222>(5y.
<223> Xaa = D-Phe
<220>
<221> MISC_FEATU RE
<222>(9).
<223> Xaa = beta-Ala
<220>
<221>RMSC_FEATURE
<222>(10yi10)
<223> Xaa = Tyr veya bulunmayan
<220>
<22t>MOD_RES
<222>(20yi20)
<223> AMI
<400> 142
<210> 143
<211> 18
DASYON
Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Giy Arg Lys Arg Arg Arg10
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221› ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221› MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221› MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221› MISC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221› MOD_RES
<222> (18)..(18)
<223> AMIDASYON
<400> 143
Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Arg Arg Lys Arg Arg Gln Arg
<210> 144
<211> 18
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221>ETKIALANI
<222>(2yls)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (18)..(18)
<223> AMIDASYON
<400>144
Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Arg Lys Arg Arg Arg Gln Arg
1 5 10 15
<210> 145
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MlSC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (20)..(20)
<223> AMIDASYON
<400> 145
Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Tyr Gly Arg Lys Lys Arg Gln
1 5 10 15
<210> 146
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATU RE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MlSC_FEATURE
<222> (9)..(9)
<223> Xaa = 8-amino-3,6-dioksa0ktanoik asit (Doc)
<220>
<221> MOD_RES
<222> (20)..(20)
<223> AMIDASYON
<400> 146
Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Ty:: Gly Arg Lys Lys Arg Arg
J. 5 10 15
<210> 147
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATU RE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MlSC_FEATURE
<222> (10)..(10)
<223> Xaa = Tyr veya bulunmayan
<220>
<221> MOD_RES
<222> (20)..(20)
<223> AMIDASYON
<400> 147
Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Gly Arg Arg Arg Arg Arg
J. 5 10 15
<210> 148
<211> 19
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATU RE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MlSC_FEATURE
<222> (10)..(10)
<223> Xaa = beta-Ala veya bulunmayan
<220>
<221> MOD_RES
<222> (19)..(19)
<223> AMIDASYON
<400> 148
Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Arg Arg Arg Arg Arg Gln
<210> 149
<211> 21
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222>(1yi1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (9)..(10)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (11)..(11)
<223> Xaa = Tyr veya bulunmayan
<220>
<221> MOD_RES
<222>(21y421)
<223> AMIDASYON
<400> 149
Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Xaa Gly Arg Arg Arg Arg
1 5 10 15
Arg Gln Arg Arg Arg<210> 150
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü ligandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = 8-amin0-3,6-di0ksa0ktanoik asit (Doc)
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = Tyr veya bulunmayan
<220>
<221> MOD_RES
<222>(20y420)
<223> AMIDASYON
<400> 150
Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Gly Arg Arg Arg Arg Arg
J. 5 10 15
<210> 151
<211> 19
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = 8-amin0-3,6-di0ksa0ktanoik asit (Doc)
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = 8-amin0-3,6-dioksa0ktanoik asit (Doc) veya bulunmayan
<220>
<221> MOD_RES
<222>(19y419)
<223> AMIDASYON
<400> 151
Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Arg Arg Arg Arg Arg 6111
1 5 10 15
<210> 152
<211> 21
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222>(2y48)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATU RE
<222> (9)..(10)
<223> Xaa = 8-amin0-3,6-dioksa0ktanoik asit (Doc)
<220>
<221> MISC_FEATURE
<222> (11)..(11)
<223> Xaa = Tyr veya bulunmayan
<220>
<221> MOD_RES
<222> (21)..(21)
<223> AMIDASYON
<400> 152
Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Xaa Gly Arg Arg Arg Arg
1 5 10 15
Arg Gln Arg Arg Arg<210> 153
<211> 21
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATU RE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = Tyr veya bulunmayan
<220>
<221> MOD_RES
<222> (21)..(21)
<223> AMIDASYON
<400> 153
Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Gly Arg Arg Arg Arg Arg
1 5 10 15
<210> 154
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATU RE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = beta-Ala veya bulunmayan
<220>
<221> MOD_RES
<222> (20)..(20)
<223> AMIDASYON
<400> 154
Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Arg Arg Arg Arg Arg Gin
1 5 10 15
<211> 22
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATU RE
<222> (9)..(10)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (11)..(11)
<223> Xaa = Tyr veya bulunmayan
<220>
<221> MOD_RES
<222> (22)..(22)
<223> AMIDASYON
<400> 155
Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Xaa Gly Arg Arg Arg Arg
1 5 10 15
<211> 21
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATU RE
<222> (9)..(9)
<223> Xaa = 8-amin0-3,6-dioksa0ktanoik asit (Doc)
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = Tyr veya bulunmayan
<220>
<221> MOD_RES
<222> (21)..(21)
<223> AMIDASYON
<400> 156
Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Gly Arg Arg Arg Arg Arg
1 5 10 15
<210> 157
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATU RE
<222> (9)..(9)
<223> Xaa = 8-amin0-3,6-dioksa0ktanoik asit (Doc)
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = 8-amino-3,6-dioksaoktan0ik asit (Doc) veya bulunmayan
<220>
<221> MOD_RES
<222> (20)..(20)
<223> AMIDASYON
<400> 157
Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Arg Arg Arg Arg Arg Gin
1 5 10 15
<211> 22
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATU RE
<222> (9)..(10)
<223> Xaa = 8-amin0-3,6-dioksa0ktanoik asit (Doc)
<220>
<221> MISC_FEATURE
<222> (11)..(11)
<223> Xaa = Tyr veya bulunmayan
<220>
<221> MOD_RES
<222> (22)..(22)
<223> AMIDASYON
<400> 158
Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Xaa Gly Arg Arg Arg Arg
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-aminobütrik asit (Gaba)
<220>
<221> MISC_FEATU RE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (20)..(20)
<223> AMIDASYON
<400> 159
Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Tyr Giy Arg Arg Arg Arg Arg
Sin Arg Arg Arg<210> 160
<211> 18
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-aminobütrik asit (Gaba)
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (18)..(18)
<223> AMIDASYON
<400> 160
Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Arg Arg Arg Arg Arg Gin Arg
<210> 161
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (20)..(20)
<223> AMIDASYON
<400> 161
Xaa Asp His Xaa Arg Trp Ala Lys Xaa Ty: Gly Arg Arg Arg Arg Arg
<210>162
<211>18
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (18)..(18)
<223> AMIDASYON
<400> 162
Xaa Asp His Xaa Arg Trp Ala Lys Xaa Arg Arg Arg Arg Arg Gln Arg
1 5 10 15
<210> 163
<211> 18
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MlSC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221› ETKI ALANI
<222>(2le)
<223> Siklik
<220>
<221› MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221› MlSC_FEATURE
<222> (8)..(8)
<223> Xaa = beta-Ala
<220>
<221› MISC_FEATURE
<222> (9)..(9)
<223> Xaa = Gly veya bulunmayan
<220>
<221› MOD_RES
<222>(18yll8)
<223> AMIDASYON
<400> 163
Xaa Asp His Xaa Arg Trp Lys Xaa Xaa Arg Arg Arg Arg Arg Gln Arg
<210> 164
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221› MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221› ETKI ALANI
<222> (2)..(7)
<223> Siklik
<220>
<221> MISC_FEATU RE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = beta-Ala
<220>
<221> MlSC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala veya bulunmayan
<220>
<221> MOD_RES
<222> (20)..(20)
<223> AMIDASYON
<400> 164
Xaa Asp His Xaa Arg Trp Lys Xaa Xaa Ty:: Gly Arg Arg Arg Arg Arg
J. 5 10 15
<210>165
<211>19
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(7)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATU RE
<222> (8)..(10)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = Gly veya bulunmayan
<220>
<221> MOD_RES
<222>(19)(19)
<223> AMIDASYON
<400> 165
Xaa Asp His Xaa Arg Trp Lys Xaa Xaa Xaa Arg Arg Arg Arg Arg Gln
1 5 10 15
<210> 166
<211> 19
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(7)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = 8-amino-3,6-dioksaoktan0ik asit (Doc)
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = Tyr veya bulunmayan
<220>
<221> MOD_RES
<222> (19)..(19)
<223> AMIDASYON
<400> 166
Xaa Asp His Xaa Arg Trp Lys Xaa Xaa Gly Arg Arg Arg Arg Arg Gln
1 5 10 15
<210> 167
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(7)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (8)..(9)
<223> Xaa = 8-amino-3,6-dioksa0ktan0ik asit (Doc)
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = Tyr veya bulunmayan
<220>
<221> MOD_RES
<222> (20)..(20)
<223> AMIDASYON
<400> 167
Xaa Asp His Xaa Arg Trp Lys Xaa Xaa Xaa Gly Arg Arg Arg Arg Arg
l 5 10 15
Gln Arg Arg Arg<210> 168
<211> 18
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MlSC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222>(2)(7)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MlSC_FEATURE
<222> (8)..(8)
<223> Xaa = 8-amino-3,6-di0ksaoktanoik asit (Doc)
<220>
<221> MlSC_FEATURE
<222> (9)..(9)
<223> Xaa = 8-amin0-3,6-dioksa0ktanoik asit (Doc) veya bulunmayan
<220>
<221> MOD_RES
<222> (18)..(18)
<223> AMIDASYON
<400> 168
Xaa Asp His Xaa Arg Trp Lys Xaa Xaa Arg Arg Arg Arg Arg Gln Arg
1 5 10 15
<210> 169
<211>19
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221› ETKI ALANI
<222> (2)..(7)
<223> Siklik
<220>
<221› MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221› MISC_FEATURE
<222> (8)..(8)
<223> Xaa = beta-Ala
<220>
<221› MISC_FEATURE
<222> (9)..(9)
<223> Xaa = Gly veya bulunmayan
<220>
<221› MOD_RES
<222> (19)..(19)
<223> AMIDASYON
<400> 169
Xaa Asp His Xaa Arg Trp Lys Xaa Xaa Arg Arg Arg Arg Arg Gln Arg
1 5 10 15
<210> 170
<211> 21
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220> _
<221> ETKI ALANI
<222> (2)..(7)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala veya bulunmayan
<220>
<221> MOD_RES
<222> (21)..(21)
<223> AMlDASYON
<400> 170
Xaa Asp His Xaa Arg Trp Lys Xaa Xaa Tyr Giy Arg Arg Arg Arg Arg
l 5 10 15
<210> 171
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi Için kullanilan melanokortin reseptörü ligandi
<220>
<221> MISC_FEATURE
<222>(1yl1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(7)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MlSC_FEATURE
<222> (8)..(9)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = Gly veya bulunmayan
<220>
<221> MOD_RES
<222> (20)..(20)
<223> AMIDASYON
<400> 171
Xaa Asp His Xaa Arg Trp Lys Xaa Xaa Xaa Arg Arg Arg Arg Arg Gln
1 5 10 15
<211> 19
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis NIe
<220>
<221> ETKI ALANI
<222> (2)..(7)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = 8-amin0-3,6-di0ksaoktan0ik asit (Doc)
<220>
<221> MlSC_FEATURE
<222> (9)..(9)
<223> Xaa = Gly veya bulunmayan
<220>
<221> MOD_RES
<222> (19)..(19)
<223> AMIDASYON
<400> 172
Xaa Asp His Xaa Arg Trp Lys Xaa Xaa Arg Arg Arg Arg Arg Gln Arg
1 5 10 15
<210> 173
<211> 21
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(7)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = 8-amino-3,6-di0ksa0ktan0ik asit (Doc)
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = 8-amin0-3,6-di0ksa0ktanoik asit (Doc) veya bulunmayan
<220>
<221> MOD_RES
<222> (21)..(21)
<223> AMIDASYON
<400> 173
Xaa Asp His Xaa Arg Trp Lys Xaa Xaa Tyr Gly Arg Arg Arg Arg Arg
<210> 174
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(7)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (8)..(9)
<223> Xaa = 8-amino-3,6-di0ksaoktan0ik asit (Doc)
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = Gly veya bulunmayan
<220>
<221> MOD_RES
<222> (20)..(20)
<223> AMIDASYON
<400> 174
xaa Asp His Xaa Arg Trp Lys Xaa Xaa Xaa Arg Arg Arg Arg Arg Gin
<210> 175
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (20)..(20)
<223> AMIDASYON
<400> 175
Xaa Asp His Xaa Arg Trp Xaa Lys Xaa Tyr Gly Arg Arg Arg Arg Arg
l 5 10 15
Gln Arg Arg Arg<210> 176
<211> 18
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MlSC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222>(2118)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MlSC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-Ala
<220>
<221> MlSC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (18)..(18)
<223> AMIDASYON
<400> 176
Xaa Asp His Xaa Arg Trp Xaa Lys Xaa Arg Arg Arg Arg Arg Gln Arg
1 5 10 15
<210> 177
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222>(7ii7)
<223> Xaa = B-aminohekzanoik asit (Ahx)
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (20)..(20)
<223> AMIDASYON
<400> 177
Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Tyr Gly Arg Arg Arg Arg Arg
1 5 10 15
Gln Arg Arg Arg<210> 178
<211> 18
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 6-amin0hekzanoik asit (Ahx)
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (18)..(18)
<223> AMIDASYON
<400> 178
Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Arg Arg Arg Arg Arg Gln Arg
1 5 10 15
<210> 179
<211> 21
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Phe
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MlSC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (21)..(21)
<223> AMIDASYON
<400> 179
Xaa Cys His Xaa Arg Trp Xaa Xaa Thr Xaa Tyr Gly Arg Arg Arg Arg
<210> 180
<211> 19
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Phe
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MlSC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (19)..(19)
<223> AMIDASYON
<400> 180
Xaa Cys His Xaa Arg Trp Xaa Xaa Thr Xaa Arg Arg Arg Arg Arg Gin
<210> 181
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 5-amin0pentanoik asit (Apn)
<220>
<221> MlSC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (20)..(20)
<223> AMIDASYON
<400> 181
Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Tyr Giy Arg Arg Arg Arg Arg
1 5 10 15
<210> 182
<211> 18
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221› MISC_FEATURE
<222>(7›47)
<223> Xaa = 5-amin0pentanoik asit (Apn)
<220>
<221› MISC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221› MOD_RES
<222>(18y418)
<223> AMIDASYON
<400> 182
Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Arg Arg Arg Arg Arg Gln Arg
<210> 183
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221>RMSC_FEATURE
<222>(1yi1)
<, veya Nle, tümü
<220>
<221>ETKIALANI
<222>(2y48)
<223> Siklik
<220>
<221› MlSC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221› MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-amin0bütrik asit (Gaba)
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222>(20y420)
<223> AMIDASYON
<400> 183
Xaa Asp His Xaa Arg Trp Xaa Lys Xaa Tyr Gly Arg Arg Arg Arg Arg
<210> 184
<211> 18
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = beta-sikloheksiIAla (Cha) veya homo-sikloheksilAIa (hCha), her ikisi de
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-aminobütrik asit (Gaba)
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (18)..(18)
<223> AMIDASYON
<400> 184
Xaa Asp His Xaa Arg Trp Xaa Lys Xaa Arg Arg Arg Arg Arg Gln Arg
<210> 185
<211> 18
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222>(1yi1)
<223> Xaa = Nle veya sikloheksilGIy (Chg), her ikisi de asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-aminobütrik asit (Gaba)
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (18)..(18)
<223> AMIDASYON
<400> 185
Xaa Asp His Xaa Arg Trp Xaa Lys Xaa Arg Arg Arg Arg Arg Gln Arg
<210> 186
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = sikloheksilGly (Chg) veya homo-sikloheksilAla (hCha), her ikisi de asil
(MMbmwmwewmß
<220>
<221>ETKIALANI
<222>(2yis)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221>RMSC_FEATURE
<222>(7ii7)
<223> Xaa = 4-amin0bütrik asit (Gaba)
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222>(20y420)
<223> AMIDASYON
<400> 186
Xaa Asp His Xaa Arg Trp Xaa Lys Xaa Tyr Gly Arg Arg Arg Arg Arg
<210> 187
<211> 21
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MlSC_FEATURE
<222> (1)..(1)
<223> Xaa = homo-sikloheksilAla (hCha) asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATU RE
<222> (7)..(7)
<223> Xaa = 4-aminobütrik asit (Gaba)
<220>
<221> MISC_FEATURE
<222> (9)..(10)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (21)..(21)
<223> AMIDASYON
<400> 187
Xaa Asp His Xaa Arg Trp Xaa Lys Xaa Xaa Tyr Gly Arg Arg Arg Arg
Arg Gln Arg Arg Arg<210> 188
<211> 19
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = homo-sikloheksiIAla (hCha) asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-aminobütrik asit (Gaba)
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = beta-Ala veya bulunmayan
<220>
<221> MOD_RES
<222> (19)..(19)
<223> AMIDASYON
<400> 188
xaa Asp His Xaa Arg Trp Xaa Lys Xaa Xaa Arg Arg Arg Arg Arg Gin
1 5 10 15
<210> 189
<211> 21
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = homo-sikloheksilAIa (hCha) asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-amin0bütrik asit (Gaba)
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = 8-amino-3,6-dioksa0ktan0ik asit (Doc)
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = 8-amino-3,6-dioksaoktanoik asit (Doc) veya bulunmayan
<220>
<221> MOD_RES
<222> (21)..(21)
<223> AMIDASYON
<400> 189
Xaa Asp His Xaa Arg Trp Xaa Lys Xaa Xaa Tyr Gly Arg Arg Arg Arg
1 5 10 15
Arg Gln Arg Arg Arg<210> 190
<211> 19
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = homo-sikloheksilAIa (hCha) asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-amin0bütrik asit (Gaba)
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = 8-amino-3,6-dioksaoktan0ik asit (Doc)
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = 8-amino-3,6-dioksaoktanoik asit (Doc) veya bulunmayan
<220>
<221> MOD_RES
<222> (19)..(19)
<223> AMIDASYON
<400> 190
Xaa Asp His Xaa Arg Trp Xaa Lys Xaa Xaa Arg Arg Arg Arg Arg Gln
1 5 10 15
<210> 191
<211> 22
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATU RE
<222> (1)..(1)
<223> Xaa = homo-sikloheksilAIa (hCha) asil (Ac) ile modifiye edilmis
<220>
<221>ETKIALANI
<222>(2yls)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MlSC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-amin0bütrik asit (Gaba)
<220>
<221> MlSC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MlSC_FEATURE
<222> (10)..(10)
<223> Xaa = beta-Ala veya bulunmayan
<220>
<221> MOD_RES
<222>(2zyl22)
<223> AMIDASYON
<400> 191
Xaa Asp His Xaa Arg Trp Xaa Lys Xaa Xaa Tyr Gly Arg Arg Arg Arg
1 5 10 15
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MlSC_FEATU RE
<222> (1)..(1)
<223> Xaa = homo-sikloheksilAIa (hCha) asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MlSC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-amin0bütrik asit (Gaba)
<220>
<221> MlSC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MlSC_FEATURE
<222> (10)..(10)
<223> Xaa = beta-Ala veya bulunmayan
<220>
<221> MOD_RES
<222> (20)..(20)
<223> AMIDASYON
<400> 192
Xaa Asp His Xaa Arg Trp Xaa Lys Xaa Xaa Arg Arg Arg Arg Arg 6111
1 5 10 15
<210> 193
<211> 22
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MlSC_FEATURE
<222> (1)..(1)
<223> Xaa = homo-sikloheksilAIa (hCha) asil (Ac) ile modifiye edilmis
<220>
<221>ETKIALANI
<222>(2yls)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MlSC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-amin0bütrik asit (Gaba)
<220>
<221> MlSC_FEATURE
<222> (9)..(9)
<223> Xaa = 8-amino-3,6-di0ksaoktanoik asit (Doc)
<220>
<221> MlSC_FEATURE
<222> (10)..(10)
<223> Xaa = 8-amino-3,6-di0ksaoktanoik asit (Doc) veya bulunmayan
<220>
<221> MOD_RES
<222>(2zyl22)
<223> AMIDASYON
<400> 193
Xaa Asp His Xaa Arg Trp Xaa Lys Xaa Xaa Tyr Gly Arg Arg Arg Arg
1 5 10 15
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MlSC_FEATU RE
<222> (1)..(1)
<223> Xaa = homo-sikloheksilAIa (hCha) asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MlSC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-amin0bütrik asit (Gaba)
<220>
<221> MlSC_FEATURE
<222> (9)..(9)
<223> Xaa = 8-amino-3,6-di0ksaoktanoik asit (Doc)
<220>
<221> MlSC_FEATURE
<222> (10)..(10)
<223> Xaa = 8-amino-3,6-di0ksaoktanoik asit (Doc) veya bulunmayan
<220>
<221> MOD_RES
<222> (20)..(20)
<223> AMIDASYON
<400> 194
Xaa Asp His Xaa Arg Trp Xaa Lys Xaa Xaa Arg Arg Arg Arg Arg Gln
1 5 10 15
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MlSC_FEATU RE
<222> (1)..(1)
<223> Xaa = D-sikloheksilGly (D-Chg) asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MlSC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-amin0bütrik asit (Gaba)
<220>
<221> MlSC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (20)..(20)
<223> AMIDASYON
<400> 195
Xaa Asp His Xaa Arg Trp Xaa Lys Xaa Tyr Gly Arg Arg Arg Arg Arg
J. 5 10 15
Gln Arg Arg Arg<210> 196
<211> 18
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü ligandi
<220>
<221> MlSC_FEATURE
<222> (1)..(1)
<223> Xaa = D-sikloheksilGly (D-Chg) asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222>(2yis)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MlSC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-aminobütrik asit (Gaba)
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (18)..(18)
<223> AMIDASYON
<400> 196
Xaa Asp His Xaa Arg Trp Xaa Lys Xaa Arg Arg Arg Arg Arg Gln Arg
1 5 10 15
<210> 197
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MlSC_FEATURE
<222> (1)..(1)
< ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-aminobütrik asit (Gaba)
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222>(20y420)
<223> AMIDASYON
<400> 197
Xaa Asp His Xaa Arg Trp Xaa Lys Xaa Tyr Gly Arg Arg Arg Arg Arg
1 5 10 15
<210> 198
<211> 18
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi Için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
< ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-aminobütrik asit (Gaba)
<220>
<221> MISC_FEATU RE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (18)..(18)
<223> AMIDASYON
<400> 198
Xaa Asp His Xaa Arg Trp Xaa Lys Xaa Arg Arg Arg Arg Arg Gln Arg
1 5 10 15
<210> 199
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MlSC_FEATURE
<222> (6)..(6)
<223> Xaa = D-Trp
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 5-aminopentanoik asit (Apn) veya ö-aminohekzanoik asit (Ahx)
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (20)..(20)
<223> AMIDASYON
<400> 199
Xaa Cys His Xaa Arg Xaa Xaa Cys Xaa Tyr Gly Arg Arg Arg Arg Arg
l 5 10 15
<210> 200
<211> 18
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (6).. (6)
<223> Xaa = D-Trp
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 5-aminopentanoik asit (Apn) veya ö-aminohekzanoik asit (Ahx)
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (18)..(18)
<223> AMIDASYON
<400> 200
<210> 201
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222>(1yi1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = D-Trp
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
Xaa Cys His Xaa Arg Xaa Xaa Cys Xaa Arg Arg Arg Arg Arg Gln Arg
<222>(20yl20)
<223> AMIDASYON
<400> 201
Xaa Cys His Xaa Arg Xaa Xaa Cys Xaa Tyr Gly Arg Arg Arg Arg Arg
<210> 202
<211> 18
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = D-Trp
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (18)..(18)
<223> AMIDASYON
<400> 202
xaa Cys His xaa Arg xaa xaa Cys xaa Arg Arg Arg Arg Arg Gin Arg
<210> 203
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MlSC_FEATURE
<222> (8)..(8)
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = Tyr veya bulunmayan
<220>
<221> MOD_RES
<222> (20)..(20)
<223> AMIDASYON
<400> 203
Xaa Cys Xaa His Xaa Arg Trp Xaa Xaa Xaa Gly Arg Arg Arg Arg Arg
<210> 204
<211> 21
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<220>
<221> MISC_FEATURE
<222> (9)..(10)
<223> Xaa = beta-Ala
<220>
<221› MISC_FEATURE
<222>(11yi11)
<223> Xaa = Tyr veya bulunmayan
<220>
<221› MOD_RES
<222>(21y421)
<223> AMIDASYON
<400> 204
Xaa Cys Xaa His Xaa Arg Trp Xaa Xaa Xaa Xaa Giy Arg Arg Arg Arg
<210> 205
<211> 19
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221› MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221› ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221› MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221› MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221› MISC_FEATURE
<222> (8)..(8)
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = beta-Ala veya bulunmayan
<220>
<221> MOD_RES
<222> (19)..(19)
<223> AMIDASYON
<400> 205
Xaa Cys Xaa His Xaa Arg Trp Xaa Xaa Xaa Arg Arg Arg Arg Arg Gln
<210> 206
<211> 19
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221>AMSC_FEATURE
<222>(5yl5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = 8-amin0-3,6-dioksa0ktan0ik asit (Doc)
<220>
<221> MlSC_FEATURE
<222> (10)..(10)
<223> Xaa = Gly veya bulunmayan
<220>
<221> MOD_RES
<222> (19)..(19)
<223> AMIDASYON
<400> 206
Xaa Cys Xaa His Xaa Arg Trp Xaa Xaa Xaa Arg Arg Arg Arg Arg Gin
1 5 10 15
<210> 207
<211> 21
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATU RE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<220>
<221> MlSC_FEATURE
<222> (9)..(9)
<223> Xaa = 8-amino-3,6-dioksa0ktanoik asit (Doc)
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = &amino-3,6-di0ksaoktanoik asit (Doc) veya bulunmayan
<220>
<221> MOD_RES
<222> (21)..(21)
<223> AMIDASYON
<400> 207
Xaa Cys Xaa His Xaa Arg Trp Xaa Xaa Xaa Tyr Giy Arg Arg Arg Arg
1 5 10 15
<210> 208
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATU RE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MlSC_FEATURE
<222> (8)..(8)
<220>
<221> MISC_FEATURE
<222> (9)..(10)
<223> Xaa = &amino-3,6-di0ksaoktanoik asit (Doc)
<220>
<221> MISC_FEATURE
<222> (11)..(11)
<223> Xaa = Gly veya bulunmayan
<220>
<221> MOD_RES
<222> (20)..(20)
<223> AMIDASYON
<400> 208
Xaa Cys Xaa His Xaa Arg Trp Xaa Xaa Xaa Xaa Arg Arg Arg Arg Arg
Gln Arg Arg Arg<210> 209
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Phe
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222>(4yi4)
<223> Xaa = D-(Et)Tyr
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-Ala
<220>
<221> MlSC_FEATURE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = Tyr veya bulunmayan
<220>
<221> MOD_RES
<222> (20)..(20)
<223> AMIDASYON
<400> 209
Xaa Cys His Xaa Arg Trp Xaa Xaa Xaa Xaa Gly Arg Arg Arg Arg Arg
i 5 10 15
<210> 210
<211> 18
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Phe
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-(Et)Tyr
<220>
<221> MlSC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (18)..(18)
<223> AMIDASYON
<400> 210
Xaa Cys His Xaa Arg Trp Xaa Xaa Xaa Arg Arg Arg Arg Arg Gln Arg
<210> 211
<211> 19
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Phe
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-(Et)Tyr
<220>
<221> MlSC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (19)..(19)
<223> AMIDASYON
<400> 211
Xaa Cys His Xaa Arg Trp Xaa Xaa Xaa Arg Arg Arg Arg Arg Gin Arg
<210> 212
<211> 21
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Phe
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-(Et)Tyr
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-Ala
<220>
<221> MlSC_FEATURE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MISC_FEATURE
<222> (9)..(10)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (21)..(21)
<223> AMIDASYON
<400> 212
Xaa Cys His Xaa Arg Trp Xaa Xaa Xaa Xaa Tyr Giy Arg Arg Arg Arg
<210> 213
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Phe
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222>(4yi4)
<223> Xaa = D-(Et)Tyr
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-Ala
<220>
<221> MlSC_FEATURE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MISC_FEATURE
<222> (9)..(10)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (11)..(11)
<223> Xaa = Gly veya bulunmayan
<220>
<221> MOD_RES
<222> (20)..(20)
<223> AMIDASYON
<400> 213
Xaa Cys His Xaa Arg Trp Xaa Xaa Xaa Xaa Xaa Arg Arg Arg Arg Arg
i 5 10 15
<210> 214
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Phe
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-(Et)Tyr
<220>
<221> MlSC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = 8-amino-3,6-dioksaoktan0ik asit (Doc)
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = Tyr veya bulunmayan
<220>
<221> MOD_RES
<222> (20)..(20)
<223> AMIDASYON
<400> 214
Xaa Cys His Xaa Arg Trp Xaa Xaa Xaa Xaa Gly Arg Arg Arg Arg Arg
l 5 10 15
Gln Arg Arg Arg<210> 215
<211> 21
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATU RE
<222> (1)..(1)
<223> Xaa = D-Phe
<220>
<221>ETKIALANI
<222>(2)(8)
<223> Siklik
<220>
<221> MlSC_FEATU RE
<222> (4)..(4)
<223> Xaa = D-(Et)Tyr
<220>
<221> MISC_FEATU RE
<222> (7)..(7)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATU RE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MISC_FEATU RE
<222>(gyx10)
<223> Xaa = 8-amino-3,6-dioksaoktarioik asit (Doc)
<220>
<221> MISC_FEATU RE
<222>(11y411)
<223> Xaa = Tyr veya bulunmayan
<220>
<221› MOD_RES
<222> (21)..(21)
<223> AMIDASYON
<400> 215
Xaa Cys His Xaa Arg Trp Xaa Xaa Xaa Xaa Xaa Gly Arg Arg Arg Arg
<210> 216
<211> 19
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Phe
<220>
<221> ETKI ALANI
<222>(2yis)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-(Et)Tyr
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATU RE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MISC_FEATURE
<222>(9)(9)
<220>
<221>RMSC_FEATURE
<222>(10y410)
<223> Xaa = 8-amin0-3,6-dioksaoktanoik asit (Doc) veya bulunmayan
<220>
<221> MOD_RES
<222>(19y419)
<223> AMIDASYON
<400> 216
Xaa Cys His Xaa Arg Trp Xaa Xaa Xaa Xaa Arg Arg Arg Arg Arg Glri
<210> 217
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Phe
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATU RE
<222> (4)..(4)
<223> Xaa = D-(Et)Tyr
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = 8-amino-3,6-di0ksaoktan0ik asit (Doc)
<220>
<221> MISC_FEATURE
<222>(10yi10)
<223> Xaa = 8-amin0-3,6-di0ksaoktanoik asit (Doc) veya bulunmayan
<220>
<221> MOD_RES
<222> (20)..(20)
<223> AMIDASYON
<400> 217
Xaa Cys His Xaa Arg Trp Xaa Xaa Xaa Xaa Arg Arg Arg Arg Arg Gln
<211> 22
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Phe
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-(Et)Tyr
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = homo-Arg (hArg)
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (11)..(11)
<223> Xaa = beta-Ala veya bulunmayan
<220>
<221> MOD_RES
<222> (22)..(22)
<223> AMIDASYON
<400> 218
Xaa Cys His Xaa Xaa Trp Xaa Xaa Thr Xaa Xaa Tyr Gly Arg Arg Arg
1 5 10 15
<210> 219
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Phe
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-(Et)Tyr
<220>
<221> MISC_FEATU RE
<222> (5)..(5)
<223> Xaa = homo-Arg (hArg)
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATU RE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (11)..(11)
<223> Xaa = beta-Ala veya bulunmayan
<220>
<221> MOD_RES
<222> (20)..(20)
<223> AMIDASYON
<400> 219
Xaa Cys His Xaa Xaa Trp Xaa Xaa Thr Xaa Xaa Arg Arg Arg Arg Arg
<210> 220
<211> 19
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Phe
<220>
<221>ETKIALANI
<222>(2)(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-(Et)Tyr
<220>
<221> MISC_FEATU RE
<222> (5)..(5)
<223> Xaa = homo-Arg (hArg)
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MlSC_FEATURE
<222> (10)..(10)
<223> Xaa = 8-amino-3,6-di0ksaoktanoik asit (Doc)
<220>
<221> MOD_RES
<222> (19)..(19)
<223> AMIDASYON
<400> 220
Xaa Cys His Xaa Xaa Trp Xaa Xaa Thr Xaa Arg Arg Arg Arg Arg Sin
1 5 10 15
<210> 221
<211> 22
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Phe
<220>
<221> ETKI ALANI
<222>(2)48)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-(Et)Tyr
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = homo-Arg (hArg)
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-Ala
<220>
<221> MlSC_FEATURE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = &amino-3,6-di0ksaoktanoik asit (Doc)
<220>
<221> MISC_FEATURE
<222> (11)..(11)
<223> Xaa = 8-amino-3,6-di0ksaoktanoik asit (Doc) veya bulunmayan
<220>
<221> MOD_RES
<222> (22)..(22)
<223> AMIDASYON
<400> 221
Xaa Cys His Xaa Xaa Trp Xaa Xaa Thr Xaa Xaa Tyr Gly Arg Arg Arg
l 5 10 15
<211> 23
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Phe
<220>
<221> ETKI ALANI
<222>(2y48)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-(Et)Tyr
<220>
<221> MlSC_FEATURE
<222> (5)..(5)
<223> Xaa = homo-Arg (hArg)
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (11)..(11)
<223> Xaa = beta-Ala veya bulunmayan
<220>
<221> MOD_RES
<222> (23)..(23)
<223> AMIDASYON
<400> 222
Xaa Cys His Xaa. Xaa. Trp Xaa Xaa Thr Xaa Xaa Tyr Gly Arg Arg Arg
<210> 223
<211> 21
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Phe
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-(Et)Tyr
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = homo-Arg (hArg)
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = beta-Ala
<220>
<221> MlSC_FEATURE
<222> (11)..(11)
<223> Xaa = beta-Ala veya bulunmayan
<220>
<221> MOD_RES
<222> (21)..(21)
<223> AMIDASYON
<400> 223
Xaa Cys His Xaa Xaa Trp Xaa Xaa Thr Xaa Xaa Arg Arg Arg Arg Arg
l 5 10 15
<210> 224
<211> 23
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MlSC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Phe
<220>
<221> ETKI ALANI
<222>(2)(8)
<223> Siklik
<220>
<221>nmsc_FEATURE
<222>(4yi4)
<223> Xaa = D-(Et)Tyr
<220>
<221> MlSC_FEATURE
<222> (5)..(5)
<223> Xaa = homo-Arg (hArg)
<220>
<221> MlSC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-Ala
<220>
<221> MlSC_FEATURE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MlSC_FEATURE
<222> (10)..(10)
<223> Xaa = 8-amino-3,6-di0ksaoktan0ik asit (Doc)
<220>
<221>RMSC_FEATURE
<222> (11)..(11)
<223> Xaa = 8-amin0-3,6-dioksa0ktanoik asit (Doc) veya bulunmayan
<220>
<221> MOD_RES
<222> (23)..(23)
<223> AMIDASYON
<400> 224
Xaa Cys His Xaa Xaa Trp Xaa Xaa Thr Xaa Xaa Tyr Giy Arg Arg Arg
1 5 10 15
<211> 21
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222>(1yx1)
<223> Xaa = D-Phe
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-(Et)Tyr
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = homo-Arg (hArg)
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATU RE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = 8-amino-3,6-di0ksaoktan0ik asit (Doc)
<220>
<221> MlSC_FEATURE
<222> (11)..(11)
<223> Xaa = 8-amino-3,6-dioksa0ktanoik asit (Doc) veya bulunmayan
<220>
<221> MOD_RES
<222> (21)..(21)
<223> AMIDASYON
<400> 225
Xaa Cys His Xaa Xaa Trp Xaa Xaa Thr Xaa Xaa Arg Arg Arg Arg Arg
J. 5 10 15
<210> 226
<211> 22
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Phe
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-(Et)Tyr
<220>
<221> MISC_FEATU RE
<222> (5)..(5)
<223> Xaa = homo-Arg (hArg)
<220>
<221> MlSC_FEATURE
<222> (6)..(6)
<220>
<221> MlSC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-Ala
<220>
<221> MlSC_FEATURE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MlSC_FEATURE
<222> (10)..(10)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (22)..(22)
<223> AMIDASYON
<400> 226
Xaa Cys His Xaa Xaa Xaa Xaa Xaa Thr Xaa Tyr Gly Arg Arg Arg Arg
1 5 10 15
<211> 22
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MlSC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Phe
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-(Et)Tyr
<220>
<221> MlSC_FEATURE
<222> (5)..(5)
<223> Xaa = homo-Arg (hArg)
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATU RE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (11)..(11)
<223> Xaa = beta-Ala veya bulunmayan
<220>
<221> MOD_RES
<222> (22)..(22)
<223> AMIDASYON
400> 227
Xaa Cys His Xaa Xaa Xaa Xaa Xaa Thr Xaa Xaa Tyr Giy Arg Arg Arg
<210> 228
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MlSC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Phe
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (4)..(4)
<223> Xaa = D-(Et)Tyr
<220>
<221> MlSC_FEATU RE
<222> (5)..(5)
<223> Xaa = homo-Arg (hArg)
<220>
<221> MlSC_FEATURE
<222> (6)..(6)
<220>
<221> MlSC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-Ala
<220>
<221> MlSC_FEATURE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MlSC_FEATURE
<222> (10)..(10)
<223> Xaa = beta-Ala
<220>
<221> MlSC_FEATURE
<222> (11)..(11)
<223> Xaa = beta-Ala veya bulunmayan
<220>
<221> MOD_RES
<222> (20)..(20)
<223> AMIDASYON
<400> 228
xaa Cys His xaa Xaa xaa xaa xaa Thr xaa xaa Arg Arg Arg Arg Arg
Sin Arg Arg Arg<210> 229
<211> 21
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Phe
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-(Et)Tyr
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = homo-Arg (hArg)
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<220>
<221> MISC_FEATU RE
<222> (7)..(7)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MlSC_FEATURE
<222> (10)..(10)
<223> Xaa = 8-amino-3,6-dioksa0ktanoik asit (Doc)
<220>
<221> MOD_RES
<222> (21)..(21)
<223> AMIDASYON
<400> 229
Xaa Cys His Xaa Xaa Xaa Xaa Xaa Thr Xaa Tyr Gly Arg Arg Arg Arg
1 5 10 15
Arg Gln Arg Arg Arl?
<210> 230
<211> 22
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Phe
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-(Et)Tyr
<220>
<221> MISC_FEATU RE
<222> (5)..(5)
<223> Xaa = homo-Arg (hArg)
<220>
<221> MlSC_FEATURE
<222> (6)..(6)
<220>
<221> MlSC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-Ala
<220>
<221> MlSC_FEATURE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MlSC_FEATURE
<222> (10)..(10)
<223> Xaa = 8-amino-3,6-di0ksaoktanoik asit (Doc)
<220>
<221> MOD_RES
<222> (22)..(22)
<223> AMIDASYON
<400> 230
Xaa Cys His Xaa Xaa Xaa Xaa Xaa Thr Xaa Tyr Gly Arg Arg Arg Arg
1 5 10 15
<211> 22
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MlSC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Phe
<220>
<221> ETKI ALANI
<222>(2)(8)
<223> Siklik
<220>
<221> MISC_FEATU RE
<222> (4)..(4)
<223> Xaa = D-(Et)Tyr
<220>
<221> MlSC_FEATU RE
<222> (5)..(5)
<223> Xaa = homo-Arg (hArg)
<220>
<221› MISC_FEATU RE
<222> (6)..(6)
<220>
<221> MISC_FEATU RE
<222> (7)..(7)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATU RE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MISC_FEATU RE
<222> (10)..(11)
<220>
<221› MOD_RES
<222> (22)..(22)
<223> AMIDASYON
<400> 231
Xaa. Cys His Xaa Xaa Xaa Xaa Xaa Thr Xaa Xaa Tyr Gly Arg Arg Arg
<210> 232
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Phe
<220>
<221> ETKI ALANI
<222>(2yis)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-(Et)Tyr
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = homo-Arg (hArg)
<220>
<221> MISC_FEATU RE
<222> (6)..(6)
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MISC_FEATURE
<222>(10y410)
<223> Xaa = 8-amino-3,6-di0ksa0ktanoik asit (Doc)
<220>
<221> MISC_FEATURE
<222>(11y411)
<223> Xaa = 8-amin0-3,6-dioksaoktanoik asit (Doc) veya bulunmayan
<220>
<221> MOD_RES
<222>(20yi20)
<223> AMIDASYON
<400> 232
Xaa Cys His Xaa Xaa Xaa Xaa Xaa Thr Xaa Xaa Arg Arg Arg Arg Arg
<210> 233
<211> 21
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(9)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (21)..(21)
<223> AMIDASYON
<400> 233
<210> 234
<211> 19
Xaa Cys Xaa His Xaa Arg Trp Gly Cys Xaa Ty:: Gly Arg Arg Arg Arg
1 5 10 15
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MlSC_FEATU RE
<222> (1)..
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..
<223> Siklik
<220>
<221> MISC_FEATU RE
<222> (3)..
<223> Xaa = D-Ala
<220>
<221> MISC_FEATU RE
<222> (5)..
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (19)..(19)
<223> AMI
<400> 234
<210> 235
<211> 21
DASYON
Xaa Cys Xaa His Xaa Arg Trp Gly Cys Xaa Arg Arg Arg Arg Arg Gln
1 5 10 15
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATU RE
<222> (1)..(1)
<223> Xaa = NIe
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATU RE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATU RE
<222> (7)..(7)
<223> Xaa = 5-aminopentanoik asit (Apn)
<220>
<221> MISC_FEATU RE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATU RE
<222> (10)..(10)
<223> Xaa = beta-Ala veya bulunmayan
<220>
<221> MOD_RES
<222> (21)..(21)
<223> AMIDASYON
<400> 235
Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Xaa Tyr Gly Arg Arg Arg Arg
<210> 236
<211> 19
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 5-aminopentanoik asit (Apn)
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = beta-Ala veya bulunmayan
<220>
<221> MOD_RES
<222> (19)..(19)
<223> AMIDASYON
<400> 236
Xaa Cys His Xaa Arg Trp xaa Cys Xaa Xaa Arg Arg Arg Arg Arg Gin
1 5 10 15
<210> 237
<211> 22
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 5-amin0pentanoik asit (Apn)
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = beta-Ala veya bulunmayan
<220>
<221> MOD_RES
<222> (22)..(22)
<223> AMIDASYON
<400> 237
Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Xaa Tyr Gly Arg Arg Arg Arg
1 5 10 15
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 5-amin0pentanoik asit (Apn)
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = beta-Ala veya bulunmayan
<220>
<221> MOD_RES
<222> (20)..(20)
<223> AMIDASYON
<400> 238
Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Xaa Arg Arg Arg Arg Arg Gln
1 5 10 15
<211> 21
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 5-amin0pentanoik asit (Apn)
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = 8-amino-3,6-dioksaoktan0ik asit (Doc)
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = 8-amino-3,6-dioksaoktanoik asit (Doc) veya bulunmayan
<220>
<221> MOD_RES
<222> (21)..(21)
<223> AMIDASYON
<400> 239
Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Xaa Tyr Gly Arg Arg Arg Arg
1 5 10 15
Arg Gln Arg Arg Arg<210> 240
<211> 19
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 5-amin0pentanoik asit (Apn)
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = 8-amino-3,6-dioksaoktan0ik asit (Doc)
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = 8-amino-3,6-dioksaoktanoik asit (Doc) veya bulunmayan
<220>
<221> MOD_RES
<222> (19)..(19)
<223> AMIDASYON
<400> 240
Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Xaa Arg Arg Arg Arg Arg Gln
1 5 10 15
<210> 241
<211> 22
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATU RE
<222> (1)..(1)
<223> Xaa = Nle
<220>
<221>ETKIALANI
<222>(2yxs)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MlSC_FEATURE
<222> (7)..(7)
<223> Xaa = 5-amin0pentan0ik asit (Apn)
<220>
<221> MlSC_FEATURE
<222> (9)..(9)
<223> Xaa = 8-amino-3,6-di0ksaoktanoik asit (Doc)
<220>
<221> MlSC_FEATURE
<222> (10)..(10)
<223> Xaa = 8-amino-3,6-di0ksaoktanoik asit (Doc) veya bulunmayan
<220>
<221> MOD_RES
<222>(22)(22)
<223> AMIDASYON
<400> 241
Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Xaa Tyr Giy Arg Arg Arg Arg
1 5 10 15
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MlSC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MlSC_FEATURE
<222> (7)..(7)
<223> Xaa = 5-aminopentanoik asit (Apn)
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = 8-amin0-3,6-dioksaoktanoik asit (Doc)
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = 8-amino-3,6-dioksaoktan0ik asit (Doc) veya bulunmayan
<220>
<221> MOD_RES
<222> (20)..(20)
<223> AMIDASYON
<400> 242
Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Xaa Arg Arg Arg Arg Arg Gln
1 5 10 15
<211> 21
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (AC) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Leu
<220>
<221> MlSC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = beta-Ala veya bulunmayan
<220>
<221> MOD_RES
<222> (21)..(21)
<223> AMIDASYON
<400> 243
Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Tyr Gly Arg Arg Arg Arg
1 5 10 15
Arg Gln Arg Arg Arg<210> 244
<211> 19
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (AC) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATU RE
<222> (3)..(3)
<223> Xaa = D-Leu
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = beta-Ala veya bulunmayan
<220>
<221> MOD_RES
<222>(19)(19)
<223> AMlDASYON
<400> 244
Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Arg Arg Arg Arg Arg Gin
1 5 10 15
<210> 245
<211> 21
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü ligandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (AC) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Leu
<220>
<221> MlSC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = &amino-3,6-di0ksaoktanoik asit (Doc)
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = 8-amino-3,6-di0ksaoktanoik asit (Doc) veya bulunmayan
<220>
<221> MOD_RES
<222> (21)..(21)
<223> AMIDASYON
<400> 245
Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Tyr Gly Arg Arg Arg Arg
1 5 10 15
Arg Gln Arg Arg Arg<210> 246
<211> 19
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (AC) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Leu
<220>
<221> MlSC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = 8-amin0-3,6-di0ksaoktanoik asit (Doc)
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = 8-amino-3,6-di0ksa0ktanoik asit (Doc) veya bulunmayan
<220>
<221> MOD_RES
<222> (19)..(19)
<223> AMIDASYON
<400> 246
Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Arg Arg Arg Arg Arg Gln
1 5 10 15
<210> 247
<211> 22
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Leu
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MlSC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = beta-Ala veya bulunmayan
<220>
<221> MOD_RES
<222> (22)..(22)
<223> AMIDASYON
<400> 247
Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Tyr Giy Arg Arg Arg Arg
1 5 10 15
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Leu
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MlSC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = beta-Ala veya bulunmayan
<220>
<221> MOD_RES
<222> (20)..(20)
<223> AMIDASYON
<400> 248
Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Arg Arg Arg Arg Arg Gln
1 5 10 15
<210> 249
<211> 22
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Leu
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MlSC_FEATURE
<222> (9)..(9)
<223> Xaa = 8-amino-3,6-dioksa0ktanoik asit (Doc)
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = &amino-3,6-di0ksaoktanoik asit (Doc) veya bulunmayan
<220>
<221> MOD_RES
<222> (22)..(22)
<223> AMIDASYON
<400> 249
Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Tyr Giy Arg Arg Arg Arg
1 5 10 15
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATU RE
<222> (3)..(3)
<223> Xaa = D-Leu
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MlSC_FEATURE
<222> (9)..(9)
<223> Xaa = 8-amino-3,6-dioksa0ktanoik asit (Doc)
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = &amino-3,6-di0ksaoktanoik asit (Doc) veya bulunmayan
<220>
<221> MOD_RES
<222> (20)..(20)
<223> AMIDASYON
<400> 250
Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Arg Arg Arg Arg Arg Gln
1 5 10 15
<211> 21
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATU RE
<222> (3)..(3)
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MlSC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = beta-Ala veya bulunmayan
<220>
<221> MOD_RES
<222> (21)..(21)
<223> AMIDASYON
<400> 251
Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Tyr Giy Arg Arg Arg Arg
1 5 10 15
Arg Gln Arg Arg Arg<210> 252
<211> 19
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATU RE
<222> (3)..(3)
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MlSC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = beta-Ala veya bulunmayan
<220>
<221> MOD_RES
<222> (19)..(19)
<223> AMIDASYON
<400> 252
Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Arg Arg Arg Arg Arg Gln
1 5 10 15
<210> 253
<211> 21
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MlSC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis NIe
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-beta-sikloheksilAla (D-Cha)
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = 8-amin0-3,6-dioksa0ktanoik asit (Doc)
<220>
<221> MlSC_FEATURE
<222> (10)..(10)
<223> Xaa = 8-amino-3,6-dioksa0ktanoik asit (Doc) veya bulunmayan
<220>
<221> MOD_RES
<222> (21)..(21)
<223> AMIDASYON
<400> 253
Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Ty: Giy Arg Arg Arg Arg
1 5 10 15
Arg Gln Arg Arg Arg<210> 254
<211> 19
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (AC) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATU RE
<222> (3)..(3)
<223> Xaa = beta-sikloheksilAla (D-Cha)
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = 8-amin0-3,6-dioksa0ktanoik asit (Doc)
<220>
<221> MlSC_FEATURE
<222> (10)..(10)
<223> Xaa = 8-amino-3,6-dioksa0ktanoik asit (Doc) veya bulunmayan
<220>
<221> MOD_RES
<222> (19)..(19)
<223> AMIDASYON
<400> 254
Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Arg Arg Arg Arg Arg Gin
1 5 10 15
<210> 255
<211> 22
<212> PRT
213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MlSC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-beta-sikloheksilAla (D-Cha)
<220>
<221> MISC_FEATU RE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MlSC_FEATURE
<222> (10)..(10)
<220>
<221> MOD_RES
<222> (22)..(22)
<223> AMIDASYON
<400> 255
Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Tyr Gly Arg Arg Arg Arg
<210> 256
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-beta-sikloheksilAla (D-Cha)
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = beta-Ala veya bulunmayan
<220>
<221> MOD_RES
<222>(20y420)
<223> AMIDASYON
<400> 256
Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Arg Arg Arg Arg Arg Gin
<211> 22
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis NIe
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-beta-sikloheksilAla (D-Cha)
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = 8-amin0-3,6-di0ksa0ktanoik asit (Doc)
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = 8-amin0-3,6-dioksa0ktanoik asit (Doc) veya bulunmayan
<220>
<221> MOD_RES
<222>(22y422)
<223> AMIDASYON
<400> 257
Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Tyr Gly Arg Arg Arg Arg
1 5 10 15
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Asil (Ac) ile modifiye edilmis Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-beta-sikloheksilAla (D-Cha)
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = 8-amin0-3,6-di0ksa0ktanoik asit (Doc)
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = 8-amin0-3,6-dioksa0ktanoik asit (Doc) veya bulunmayan
<220>
<221> MOD_RES
<222> (20)..(20)
<223> AMIDASYON
<400> 258
Xaa Cys Xaa His Xaa Arg Trp Cys Xaa Xaa Arg Arg Arg Arg Arg Gin
1 5 10 15
<211> 21
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATU RE
<222> (7)..(7)
<223> Xaa = 4-amin0bütrik asit (Gaba)
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = beta-Ala veya bulunmayan
<220>
<221> MOD_RES
<222> (21)..(21)
<223> AMIDASYON
<400> 259
Arg Gln Arg Arg Arg<210> 260
<211> 19
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATU RE
<222> (7)..(7)
<223> Xaa = 4-amin0bütrik asit (Gaba)
Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Xaa Tyr Gly Arg Arg Arg Arg
10 15
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = beta-Ala veya bulunmayan
<220>
<221> MOD_RES
<222>(19y419)
<223> AMIDASYON
<400> 260
Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Xaa Arg Arg Arg Arg Arg 6111
<210> 261
<211> 22
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle
<220>
<221> ETKI ALANI
<222>(2y48)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-aminobütrik asit (Gaba)
<220>
<221> MISC_FEATU RE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = beta-Ala veya bulunmayan
<220>
<221> MOD_RES
<222> (22)..(22)
<223> AMIDASYON
<400> 261
Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Xaa Tyr Gly Arg Arg Arg Arg
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MlSC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-aminobütrik asit (Gaba)
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = beta-Ala veya bulunmayan
<220>
<221> MOD_RES
<222> (20)..(20)
<223> AMIDASYON
400> 262
Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Xaa Arg Arg Arg Arg Arg Sin
1 5 10 15
<210> 263
<211> 21
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MlSC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-amin0bütrik asit (Gaba)
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = 8-amino-3,6-di0ksaoktan0ik asit (Doc)
<220>
<221> MISC_FEATU RE
<222> (10)..(10)
<223> Xaa = 8-amin0-3,6-dioksa0ktanoik asit (Doc) veya bulunmayan
<220>
<221> MOD_RES
<222> (21)..(21)
<223> AMIDASYON
<400> 263
Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Xaa Tyr Giy Arg Arg Arg Arg
Arg Gln Arg Arg Arg<210> 264
<211> 19
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-aminobütrik asit (Gaba)
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = 8-amino-3,6-di0ksaoktan0ik asit (Doc)
<220>
<221> MISC_FEATU RE
<222> (10)..(10)
<223> Xaa = 8-amin0-3,6-dioksa0ktanoik asit (Doc) veya bulunmayan
<220>
<221> MOD_RES
<222> (19)..(19)
<223> AMIDASYON
<400> 264
Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Xaa Arg Arg Arg Arg Arg Gln
1 5 10 15
<210> 265
<211> 22
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MlSC_FEATURE
<222> (7)..(7)
<223> Xaa = 4-aminobütrik asit (Gaba)
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = 8-amino-3,6-dioksaoktan0ik asit (Doc)
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = 8-amino-3,6-di0ksa0ktari0ik asit (Doc) veya bulunmayan
<220>
<221> MOD_RES
<222> (22)..(22)
<223> AMIDASYON
<400> 265
Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Xaa Tyr Gly Arg Arg Arg Arg
1 5 10 15
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Nle
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATU RE
<222> (7)..(7)
<223> Xaa = 4-amin0bütrik asit (Gaba)
<220>
<221> MISC_FEATURE
<222> (9)..(9)
<223> Xaa = 8-amino-3,6-di0ksaoktan0ik asit (Doc)
<220>
<221> MISC_FEATURE
<222> (10)..(10)
<223> Xaa = 8-amin0-3,6-di0ksaoktanoik asit (Doc) veya bulunmayan
<220>
<221> MOD_RES
<222> (20)..(20)
<223> AMIDASYON
<400> 266
Xaa Cys His Xaa Arg Trp Xaa Cys Xaa Xaa Arg Arg Arg Arg Arg Gln
<210> 267
<211> 20
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Phe
<220>
<221> ETKI ALANI
<222> (2)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-(Et)Tyr
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-Ala
<220>
<221> MISC_FEATURE
<222> (8)..(8)
<223> Xaa = D-Cys
<220>
<221> MISC_FEATURE
<222> (9)..(10)
<223> Xaa = beta-Ala
<220>
<221> MOD_RES
<222> (20)..(20)
<223> AMIDASYON
<400> 267
xaa Cys His xaa Arg Trp xaa xaa xaa Xaa Arg Arg Arg Arg Arg Gin
1 5 10 15
<211> 12
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü ligandi
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (AC) ile modifiye edilmis
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<220>
<221> MOD_RES
<222> (12)..(12)
<223> AMIDASYON
<400> 268
Cys Glu His Xaa Arg Trp Gly Cys Pro Pro Lys Asp
<210> 269
<211> 12
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü ligandi
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> MlSC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = Trp, beta-(2-naftiI)Ala (2-Nal), beta-(1-naftiI)Ala (1 -Nal) veya 3-
benzotienilAla (Bal)
<220>
<221> MOD_RES
<222> (12)..(12)
<223> AMIDASYON
<400> 269
Cys Giu His xaa Arg xaa Aia Cys Pro Pro Lys Asp
<210> 270
<211> 12
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü ligandi
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MOD_RES
<222> (1)..(1)
<223> asil (Ac) ile modifiye edilmis
<220>
<221> MISC_FEATU RE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = beta-(2-naftiI)AIa (2-Nal)
<220>
<221> MlSC_FEATURE
<222> (7)..(7)
<223> Xaa = beta-Ala veya alfa-aminoizobütrik asit (Aib)
<220>
<221> MOD_RES
<222> (12)..(12)
<223> AMIDASYON
<400> 270
Cys Glu His Xaa Arg Xaa Xaa Cys Pro Pro Lys Asp
<210> 271
<211> 7
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> ETKI ALANI
<222> (1)..(7)
<223> Siklik
<220>
<221> MOD_RES
<222> (1)..(1)
<223> hidantoin(CO) ile modifiye edilmis
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Cys veya homosistein (hCys)
<220>
<221> MISC_FEATURE
<222> (2)..(2)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MOD_RES
<222>(7l47)
<223> AMIDASYON
<400> 271
<210> 272
<211> 7
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> ETKI ALANI
<222> (1)..(7)
<223> Siklik
<220>
<221> MOD_RES
<222> (1)..(1)
<223> hidantoin(CO) ile modifiye edilmis
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Cys veya homosistein (hCyS)
<220>
<221> MlSC_FEATURE
<222> (2)..(2)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MOD_RES
<222> (7)..(7)
<223> AMIDASYON
<400> 272
<210> 273
<211> 7
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> ETKI ALANI
<222> (1)..(7)
<223> Siklik
<220>
<221> MOD_RES
<222> (1)..(1)
<223> hidantoin(CO) ile modifiye edilmis
<220>
<221> MISC_FEATURE
<222> (2)..(2)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = Lys, ornitin (Orn), 2,4-diaminobütrik asit (Dab), veya 2,3-diamin0propi
yonik asit (Dap)
<220>
<221> MOD_RES
<222> (7)..(7)
<223> AMIDASYON
<400> 273
<210> 274
<211> 6
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> hidantoin(CO) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(6)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (2)..(2)
<, 1-amin0-1siklopentan
karboksilik asit (A50), 1-amino-1-sikloheksankarboksilik asit (AGC), 2-amin0indan-2-
karboksilik asit (Aic), veya Apc
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Phe
<220>
<221> MOD_RES
<222> (6)..(6)
<223> AMIDASYON
<400> 274
<210> 275
<211> 6
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> ETKI ALANI
<222> (1)..(6)
<223> Siklik
<220>
<221> MOD_RES
<222> (1)..(1)
<223> hidantoin(CO) ile modifiye edilmis
<220>
<221> MISC_FEATURE
<222> (2)..(2)
<, 1-amino-1sikl0pentan
karboksilik asit (A50), 1-amino-1-sikloheksankarboksilik asit (Aöc), 2-amin0indan-2-
karboksilik asit (Aic), veya Apc
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-beta-(2-naftil)AIa (D-2-Nal)
<220>
<221> MOD_RES
<222> (6)..(6)
<223> AMIDASYON
<400> 275
<210> 276
<211> 7
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> hidantoin(CO) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (1)..(7)
<223> Siklik
<221> MISC_FEATURE
<222> (2)..(2)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Phe
<220>
<221> MISC_FEATURE
<222> (7)..(7)
<223> Xaa = Lys, ornitin (Orn), 2,4-diamin0bütrik asit (Dab), veya 2,3-diamin0propi
yonik asit (Dap)
<220>
<221> MOD_RES
<222> (7)..(7)
<223> AMIDASYON
<400> 276
<210> 277
<211> 6
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> ETKI ALANI
<222> (1)..(6)
<223> Siklik
<220>
<221> MOD_RES
<222> (1)..(1)
<223> hidantoin(CO) ile modifiye edilmis
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Phe
<220>
<221> MOD_RES
<222> (6)..(6)
<223> AMlDASYON
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = Lys veya 2,3-diamin0propiyonik asit (Dap)
<400> 277
<210> 278
<211> 9
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MlSC_FEATURE
<222> (1)..(1)
<223> Xaa = Arg, norleucine (Nle), Gly, veya D-Arg
<220>
<221> MOD_RES
<222> (1)..(1)
<223> hidantoin(CO) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (3)..(9)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (6)..(6)
<223> Xaa = D-Phe
<220>
<221> MOD_RES
<222> (9)..(9)
<223> AMIDASYON
<400> 278
Xaa Gly Cys Glu His Xaa Arg Trp Cys
<210> 279
<211> 9
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MlSC_FEATU RE
<222> (1)..(1)
<223> Xaa = norleucine (Nle), Gly, Ala, D-Ala, alfa-aminoizobütrik asit (Aib), Val, Ile,
Leu, D-Arg, veya Arg
<220>
<221> MOD_RES
<222> (1)..(1)
<223> hidantoin(CO) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (3)..(9)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = D-Phe
<220>
<221> MOD_RES
<222> (9)..(9)
<223> AMIDASYON
<400> 279
Xaa Gly Cys Xaa His Xaa Arg Trp Cys
<210> 280
<211> 9
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MlSC_FEATURE
<222> (1)..(1)
<223> Xaa = norleucine (Nle) veya Gly
<220>
<221> MOD_RES
<222> (1)..(1)
<223> hidantoin(CO) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (3)..(9)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = D-Phe
<220>
<221> MlSC_FEATURE
<222> (9)..(9)
<220>
<221> MOD_RES
<222> (9)..(9)
<223> AMIDASYON
<400> 280
<210> 281
<211> 9
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = norleucine (Nle) veya Gly
<220>
<221> MOD_RES
<222> (1)..(1)
<223> hidantoin(CO) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (3)..(9)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = D-beta-(2-naftiI)AIa (D-2-Nal)
Xaa Gly Cys Xaa His Xaa Arg Trp Xaa
<220>
<221> MOD_RES
<222>(9›(9)
<223> AMIDASYON
<400> 281
xaa Gly Cys Glu His Xaa Arg Trp Cys
<210> 282
<211> 9
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = D-Arg veya Arg
<220>
<221> MOD_RES
<222> (1)..(1)
<223> hidantoin(CO) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (3)..(9)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Ala
<220>
<221> MlSC_FEATURE
<222> (6)..(6)
<223> Xaa = D-beta-(Z-naftil)AIa (D-2-Nal)
<220>
<221> MOD_RES
<222> (9)..(9)
<223> AMIDASYON
<400> 282
xaa Gly Cys Xaa His Xaa Arg Trp Cys
<210> 283
<211> 9
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MlSC_FEATURE
<222> (1)..(1)
<220>
<221> MOD_RES
<222> (1)..(1)
<223> hidantoin(CO) ile modifiye edilmis
<220>
<221> MlSC_FEATURE
<222> (2)..(2)
<223> Xaa = norleucine (Nle)
<220>
<221> ETKI ALANI
<222> (3)..(9)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (6)..(6)
<223> Xaa = D-Phe
<220>
<221> MOD_RES
<222> (9)..(9)
<223> AMIDASYON
<400> 283
Xaa Xaa Cys Glu His Xaa Arg Trp Cys
<210> 284
<211> 9
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> hidantoin(CO) ile modifiye edilmis
<220>
<221> MlSC_FEATURE
<222> (1)..(1)
<, Gly, Ala, D-Ala, Val, Leu,
beta-sikloheksilalanin (Cha), veya alfa-aminoizobütrik asit (Aib)
<220>
<221> MlSC_FEATURE
<222> (2).. (2)
<223> Xaa = norleucine (Nle)
<220>
<221> ETKI ALANI
<222> (3)..(9)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Ala
<220>
<221> MlSC_FEATURE
<222> (6)..(6)
<223> Xaa = D-Phe
<220>
<221> MOD_RES
<222> (9)..(9)
<223> AMIDASYON
<400> 284
Xaa Xaa Cys Xaa His xaa Arg Trp Cys
<210> 285
<211> 9
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> hidantoin(CO) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (3)..(9)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (6)..(6)
<223> Xaa = D-Phe veya D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MOD_RES
<222> (9)..(9)
<223> AMIDASYON
<400> 285
Gly Arg Cys Glu His Xaa Arg Trp Cys
<210> 286
<211> 9
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> hidantoin(CO) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (3)..(9)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Ala
<220>
<221> MlSC_FEATU RE
<222> (6)..(6)
<223> Xaa = D-Phe veya D-beta-(2-naftil)Ala (D-2-Nal)
<220>
<221> MOD_RES
<222>(9›(9)
<223> AMIDASYON
<400> 286
Giy Arg Cys Xaa His Xaa Arg Trp Cys
<210> 287
<211> 9
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> hidantoin(CO) ile modifiye edilmis
<220>
<221> MISC_FEATURE
<222> (2)..(2)
<223> Xaa = D-Arg
<220>
<221> ETKI ALANI
<222> (3)..(9)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = D-Phe
<220>
<221> MOD_RES
<222> (9)..(9)
<223> AMIDASYON
<400> 287
Gly Xaa Cys Glu His Xaa Arg Trp Cys
<210> 288
<211> 9
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> hidantoin(CO) ile modifiye edilmis
<220>
<221> MlSC_FEATURE
<222> (2)..(2)
<223> Xaa = D-Arg
<220>
<221> ETKI ALANI
<222> (3)..(9)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Ala
<220>
<221> MlSC_FEATU RE
<222> (6)..(6)
<223> Xaa = D-Phe veya D-beta-(Z-naftil)AIa (D-2-Nal)
<220>
<221> MOD_RES
<222>(9yl9)
<223> AMIDASYON
<400> 288
Giy Xaa Cys Xaa His Xaa Arg Trp Cys
<210> 289
<211> 9
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> hidantoin(CO) ile modifiye edilmis
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = norleucine (Nle)
<220>
<221> ETKI ALANI
<222> (3)..(9)
<223> Siklik
<220>
<221> MlSC_FEATURE
<222> (6)..(6)
<223> Xaa = D-Phe
<220>
<221> MOD_RES
<222> (9)..(9)
<223> AMIDASYON
<400> 289
Xaa Ala Cys Glu His Xaa Arg Trp Cys
<210>290
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MOD_RES
<222> (1)..(1)
<223> hidantoin(CO) ile modifiye edilmis
<220>
<221> MlSC_FEATURE
<222> (1)..(1)
<223> Xaa = norleucine (Nle), Ala. D-Ala, alfa-aminoizobütrik asit (Aib), Val, alfa-
aminobütrik asit (Abu), Leu, Ile, beta-sikloheksilalanin (Cha), 1-amin0-1-
sikloheksankarboksilik asit (Aöc), Phe veya Gly
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MISC_FEATURE
<222> (3)..(3)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDASYON
<400> 290
Xaa Cys Xaa His Xaa Arg Trp Cys
<210> 291
<211> 8
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> ETKI ALANI
<222> (1)..(8)
<223> Siklik
<220>
<221> MOD_RES
<222> (1)..(1)
<223> hidantoin(CO) ile modifiye edilmis
<220>
<221> MlSC_FEATURE
<222> (5)..(5)
<223> Xaa = D-Phe
<220>
<221> MOD_RES
<222> (8)..(8)
<223> AMIDASYON
<400> 291
Gly Cys Glu His xaa Arg Trp Cys
<210> 292
<211>9
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> MISC_FEATURE
<222> (1)..(1)
<223> Xaa = Tyr, beta-(2-naftil)alanin (2-Nal), beta-(1-naftil)alanin (1-Nal), Phe, Trp,
(8)-pentaflorofenilalanin (Pff), veya His, tümü asil (Ac) ile modifiye edilmis
<220>
<221> ETKI ALANI
<222> (3)..(9)
<223> cylic
<220>
<221> MISC_FEATURE
<222> (4)..(4)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = D-Phe
<220>
<221> MOD_RES
<222> (9)..(9)
<223> AMIDASYON
<400> 292
<210> 293
<211> 9
<212> PRT
<213> Yapay Dizi
<220>
<223> Insülin duyarliliginin tedavisi için kullanilan melanokortin reseptörü Iigandi
<220>
<221> ETKI ALANI
<222> (3)..(9)
<223> Siklik
<220>
<221> MISC_FEATURE
Xaa Arg Cys Xaa His Xaa Arg Trp Cys
<222> (4)..(4)
<223> Xaa = D-Ala
<220>
<221> MISC_FEATURE
<222> (6)..(6)
<223> Xaa = D-Phe
<220>
<221> MOD_RES
<222> (9)..(9)
<223> AMIDASYON
<400> 293
Claims (12)
1. Denekte insülin direncinin tedavisinde periferik yol ile verilen melanokortin reseptörü 4 agonisti kullanilmaktadir; burada söz konusu melanokortin reseptörü 4 agonisti: Hidantoin(C(O)-(Arg-Gly))-c(Cys-GIu-His-D-Phe-Arg-Trp-Cys)-NHz; SEQ ID No:278; veya farmasötik olarak kabul edilen tuzlaridir.
2. istem 1 'e göre kullanim için melanokortin reseptörü 4 agonisti olup, burada söz konusu denek obez veya fazla kiloludur.
3. istem 1 'e göre kullanim için melanokortin reseptörü 4 agonisti olup, burada söz konusu denek normal kilolu veya zayiftir.
4. Istem 2 veya 3 'e göre kullanim için melanokortin reseptörü 4 agonisti olup, burada söz konusu obez, fazla kilolu, normal kilolu veya zayif denek tip II diyabet hastasidir.
5. Istem 1 ila 4 ”ten herhangi birine göre kullanim için melanokortin reseptörü 4 agonisti olup, burada söz konusu periferik uygulama, agizdan, deri altina, periton içi, kas içi, damar içi, rektal, transdermal veya burun içi uygulamadir.
6. Istem 5 'e göre kullanim için melanokortin reseptörü 4 agonisti olup, burada söz konusu uygulama sürekli, saatte bir, günde dört kez, günde üç kez, günde iki kez, günde bir kez, gün asiri, haftada iki kez, haftada bir kez, iki haftada bir, ayda bir veya iki ayda bir veya daha uzun araliklar seklindedir.
7. Istem 6 'ya göre kullanim için melanokortin reseptörü 4 agonisti olup, burada söz konusu uygulama süreklidir.
8. Istem 6 'ya göre kullanim için melanokortin reseptörü 4 agonisti olup, burada söz konusu uygulama günde bir kezdir.
9. Istem 6 'ya göre kullanim için melanokortin reseptörü 4 agonisti olup, burada söz konusu uygulama haftada bir kezdir.
10. Istem 6 ,ya göre kullanim için melanokortin reseptörü 4 agonisti olup, burada söz konusu uygulama iki haftada bir kezdir.
11. istem 6 'ya göre kullanim için melanokortin reseptörü 4 agonisti olup, burada söz konusu uygulama ayda bir veya iki ayda birdir.
12. istem 1 ila 11 'den herhangi birine göre kullanim için melanokortin reseptörü 4 agonisti olup, burada söz konusu ihtiyaci olan denegin söz konusu insülin direncini tedavi etmek için melanokortin reseptörü 4 agonisti söz konusu uygulama periferik yol ile ayni zamanda ihtiyaç duyan denegin vücut agirligini da azaltir.
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| ES2618315T3 (es) * | 2007-05-25 | 2017-06-21 | Ipsen Pharma S.A.S. | Ligandos del receptor de melanocortina modificados con hidantoína |
| ES2690556T3 (es) | 2007-11-05 | 2018-11-21 | Ipsen Pharma S.A.S. | Uso de melanocortinas para tratar la sensibilidad a la insulina |
| EP2440572B1 (en) | 2009-06-08 | 2017-04-05 | Palatin Technologies, Inc. | Lactam-bridged melanocortin receptor-specific peptides |
| JP5805632B2 (ja) | 2009-06-08 | 2015-11-04 | パラティン テクノロジーズ, インコーポレイテッドPalatin Technologies, Inc. | メラノコルチン受容体に特異的なペプチド |
| IN2012DN01493A (tr) * | 2009-08-05 | 2015-06-05 | Ipsen Pharma Sas | |
| DK2473518T3 (en) * | 2009-08-31 | 2017-03-27 | Tensive Controls Inc | Stabilized melanocortin ligands |
| WO2011060352A1 (en) * | 2009-11-16 | 2011-05-19 | Ipsen Pharma S.A.S. | Pharmaceutical compositions of melanocortin receptor ligands |
| EA201290295A1 (ru) | 2009-11-23 | 2013-01-30 | Палатин Текнолоджиз, Инк. | Специфичные к рецептору меланокортина-1 линейные пептиды |
| BR112012011787B1 (pt) | 2009-11-23 | 2022-03-03 | Palatin Technologies, Inc | Peptídeo cíclico e composição farmacêutica |
| UA114088C2 (xx) | 2011-06-14 | 2017-04-25 | Лікарська композиція з пролонгованим вивільненням для ін'єкцій | |
| HRP20211950T1 (hr) * | 2011-12-29 | 2022-03-18 | Rhythm Pharmaceuticals, Inc. | Postupak liječenja poremećaja u vezi sa melanokortin-4 receptorom u heterozigotnim nosiocima |
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| JP6538025B2 (ja) | 2013-03-15 | 2019-07-03 | リズム・ファーマシューティカルズ・インコーポレイテッド | 医薬組成物 |
| US10314883B2 (en) | 2015-02-13 | 2019-06-11 | University Of Virginia Patent Foundation | Compositions and methods for regulating blood pressure |
| WO2017019952A1 (en) | 2015-07-29 | 2017-02-02 | University Of Virginia Patent Foundation | Compositions and methods for regulating leukocyte adhesion |
| WO2017049140A2 (en) | 2015-09-18 | 2017-03-23 | Wake Forest University Health Sciences | Angiotensin (1-7) analogs and methods relating thereto |
| US11124541B2 (en) * | 2016-10-18 | 2021-09-21 | Regents Of The University Of Minnesota | Chimeric melanocortin ligands and methods of use thereof |
| CA3102603A1 (en) | 2018-06-05 | 2019-12-12 | The Research Foundation For The State University Of New York | Method for passive wireless channel estimation in radio frequency network and apparatus for same |
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