JP2013512265A - 化合物の制御送達及び持続送達のためのシルク粒子 - Google Patents
化合物の制御送達及び持続送達のためのシルク粒子 Download PDFInfo
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- JP2013512265A JP2013512265A JP2012541353A JP2012541353A JP2013512265A JP 2013512265 A JP2013512265 A JP 2013512265A JP 2012541353 A JP2012541353 A JP 2012541353A JP 2012541353 A JP2012541353 A JP 2012541353A JP 2013512265 A JP2013512265 A JP 2013512265A
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- 229960004982 vinblastine sulfate Drugs 0.000 description 1
- AQTQHPDCURKLKT-JKDPCDLQSA-N vincristine sulfate Chemical compound OS(O)(=O)=O.C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C=O)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 AQTQHPDCURKLKT-JKDPCDLQSA-N 0.000 description 1
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- UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 1
- 229960004355 vindesine Drugs 0.000 description 1
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- FKBHRUQOROFRGD-IELIFDKJSA-N vinorelbine Chemical compound C1N(CC=2[C]3C=CC=CC3=NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC FKBHRUQOROFRGD-IELIFDKJSA-N 0.000 description 1
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- 229960002166 vinorelbine tartrate Drugs 0.000 description 1
- GBABOYUKABKIAF-IWWDSPBFSA-N vinorelbinetartrate Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC(C23[C@H]([C@@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-IWWDSPBFSA-N 0.000 description 1
- GXFAIFRPOKBQRV-GHXCTMGLSA-N viomycin Chemical compound N1C(=O)\C(=C\NC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)C[C@@H](N)CCCN)CNC(=O)[C@@H]1[C@@H]1NC(=N)N[C@@H](O)C1 GXFAIFRPOKBQRV-GHXCTMGLSA-N 0.000 description 1
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- 235000019165 vitamin E Nutrition 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 229940011671 vitamin b6 Drugs 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
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- BCEHBSKCWLPMDN-MGPLVRAMSA-N voriconazole Chemical compound C1([C@H](C)[C@](O)(CN2N=CN=C2)C=2C(=CC(F)=CC=2)F)=NC=NC=C1F BCEHBSKCWLPMDN-MGPLVRAMSA-N 0.000 description 1
- 229960001771 vorozole Drugs 0.000 description 1
- XLMPPFTZALNBFS-INIZCTEOSA-N vorozole Chemical compound C1([C@@H](C2=CC=C3N=NN(C3=C2)C)N2N=CN=C2)=CC=C(Cl)C=C1 XLMPPFTZALNBFS-INIZCTEOSA-N 0.000 description 1
- XOSXWYQMOYSSKB-UHFFFAOYSA-L water blue Chemical compound [Na+].[Na+].[O-]S(=O)(=O)C1=C(N)C(C)=CC(C(=C2C=CC(C=C2)=NC=2C=CC(=CC=2)S([O-])(=O)=O)C=2C=CC(NC=3C=CC(=CC=3)S(O)(=O)=O)=CC=2)=C1 XOSXWYQMOYSSKB-UHFFFAOYSA-L 0.000 description 1
- NQWBFQXRASPNLB-UHFFFAOYSA-N wine lactone Chemical compound C1CC(C)=CC2OC(=O)C(C)C21 NQWBFQXRASPNLB-UHFFFAOYSA-N 0.000 description 1
- 239000001018 xanthene dye Substances 0.000 description 1
- RKUQLAPSGZJLGP-UHFFFAOYSA-N xibenolol Chemical compound CC1=CC=CC(OCC(O)CNC(C)(C)C)=C1C RKUQLAPSGZJLGP-UHFFFAOYSA-N 0.000 description 1
- 229950001124 xibenolol Drugs 0.000 description 1
- NLIVDORGVGAOOJ-MAHBNPEESA-M xylene cyanol Chemical compound [Na+].C1=C(C)C(NCC)=CC=C1C(\C=1C(=CC(OS([O-])=O)=CC=1)OS([O-])=O)=C\1C=C(C)\C(=[NH+]/CC)\C=C/1 NLIVDORGVGAOOJ-MAHBNPEESA-M 0.000 description 1
- ORZHVTYKPFFVMG-UHFFFAOYSA-N xylenol orange Chemical compound OC(=O)CN(CC(O)=O)CC1=C(O)C(C)=CC(C2(C3=CC=CC=C3S(=O)(=O)O2)C=2C=C(CN(CC(O)=O)CC(O)=O)C(O)=C(C)C=2)=C1 ORZHVTYKPFFVMG-UHFFFAOYSA-N 0.000 description 1
- 229940051021 yellow-fever virus Drugs 0.000 description 1
- 229960004010 zaleplon Drugs 0.000 description 1
- HUNXMJYCHXQEGX-UHFFFAOYSA-N zaleplon Chemical compound CCN(C(C)=O)C1=CC=CC(C=2N3N=CC(=C3N=CC=2)C#N)=C1 HUNXMJYCHXQEGX-UHFFFAOYSA-N 0.000 description 1
- 238000000733 zeta-potential measurement Methods 0.000 description 1
- 229950007802 zidometacin Drugs 0.000 description 1
- 229960002791 zimeldine Drugs 0.000 description 1
- OYPPVKRFBIWMSX-SXGWCWSVSA-N zimeldine Chemical compound C=1C=CN=CC=1C(=C/CN(C)C)\C1=CC=C(Br)C=C1 OYPPVKRFBIWMSX-SXGWCWSVSA-N 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- 229940043810 zinc pyrithione Drugs 0.000 description 1
- PICXIOQBANWBIZ-UHFFFAOYSA-N zinc;1-oxidopyridine-2-thione Chemical compound [Zn+2].[O-]N1C=CC=CC1=S.[O-]N1C=CC=CC1=S PICXIOQBANWBIZ-UHFFFAOYSA-N 0.000 description 1
- KYNBIEFLVXTQTO-UHFFFAOYSA-L zinc;phenyl sulfate Chemical compound [Zn+2].[O-]S(=O)(=O)OC1=CC=CC=C1.[O-]S(=O)(=O)OC1=CC=CC=C1 KYNBIEFLVXTQTO-UHFFFAOYSA-L 0.000 description 1
- 229950009268 zinostatin Drugs 0.000 description 1
- 229960001360 zolmitriptan Drugs 0.000 description 1
- UTAZCRNOSWWEFR-ZDUSSCGKSA-N zolmitriptan Chemical compound C=1[C]2C(CCN(C)C)=CN=C2C=CC=1C[C@H]1COC(=O)N1 UTAZCRNOSWWEFR-ZDUSSCGKSA-N 0.000 description 1
- 229960001475 zolpidem Drugs 0.000 description 1
- ZAFYATHCZYHLPB-UHFFFAOYSA-N zolpidem Chemical compound N1=C2C=CC(C)=CN2C(CC(=O)N(C)C)=C1C1=CC=C(C)C=C1 ZAFYATHCZYHLPB-UHFFFAOYSA-N 0.000 description 1
- 229960003414 zomepirac Drugs 0.000 description 1
- ZXVNMYWKKDOREA-UHFFFAOYSA-N zomepirac Chemical compound C1=C(CC(O)=O)N(C)C(C(=O)C=2C=CC(Cl)=CC=2)=C1C ZXVNMYWKKDOREA-UHFFFAOYSA-N 0.000 description 1
- UBQNRHZMVUUOMG-UHFFFAOYSA-N zonisamide Chemical compound C1=CC=C2C(CS(=O)(=O)N)=NOC2=C1 UBQNRHZMVUUOMG-UHFFFAOYSA-N 0.000 description 1
- 229960002911 zonisamide Drugs 0.000 description 1
- WHNFPRLDDSXQCL-UAZQEYIDSA-N α-msh Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(N)=O)NC(=O)[C@H](CO)NC(C)=O)C1=CC=C(O)C=C1 WHNFPRLDDSXQCL-UAZQEYIDSA-N 0.000 description 1
- OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 description 1
- 150000003952 β-lactams Chemical class 0.000 description 1
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Abstract
【選択図】なし
Description
i)少なくとも2つの同一の反復単位を含むシルクポリペプチド、好ましくはスパイダーシルクポリペプチドを1つ又は複数含むシルク粒子、好ましくはスパイダーシルク粒子を準備する工程と、
ii)上記シルク粒子、好ましくはスパイダーシルク粒子を、水溶性であり、約50Da〜約20kDaの分子量を有する少なくとも1つの化合物とインキュベートする工程と、
を含む、化合物が装填されたシルク粒子、好ましくはスパイダーシルク粒子を製造する方法に関する。
a)少なくとも2つの同一の反復単位を含むシルクポリペプチド、好ましくはスパイダーシルクポリペプチドを1つ又は複数含む水溶液を準備する工程と、
b)該シルクポリペプチド、好ましくはスパイダーシルクポリペプチドの凝集を誘起し、シルク粒子、好ましくはスパイダーシルク粒子を形成する、誘起する工程と、
c)該シルク粒子、好ましくはスパイダーシルク粒子を相分離により分離する工程と、
により作製する。
i)GPGXX(配列番号3)(ここでXは任意のアミノ酸であり、好ましいそれぞれの場合で独立してA、S、G、Y、P及びQからなる群から選択される)、
ii)GGX(ここでXは任意のアミノ酸であり、好ましいそれぞれの場合で独立してY、P、R、S、A、T、N及びQからなる群から選択される)、及び
iii)Ax(ここでxは5〜10の整数である)
からなる群から選択されるコンセンサス配列を少なくとも1つ含む。
i)GPGXX(配列番号3)(ここでXは任意のアミノ酸であり、好ましくはそれぞれの場合で独立してA、S、G、Y、P及びQからなる群から選択される)、
ii)GGX(ここでXは任意のアミノ酸であり、好ましくはそれぞれの場合で独立してY、P、R、S、A、T、N及びQからなる群から選択される)、及び
iii)Ax(ここでxは5〜10の整数である)
からなる群から選択されるコンセンサス配列を少なくとも1つ含む。
i)少なくとも2つの同一の反復単位を含むシルクポリペプチド、好ましくはスパイダーシルクポリペプチドを1つ又は複数含むシルク粒子、好ましくはスパイダーシルク粒子を準備する工程と、
ii)上記シルク粒子、好ましくはスパイダーシルク粒子を、好ましくは水溶性であり、及び/又は約50Da〜約20kDaの分子量を有する少なくとも1つの化合物とインキュベートする工程と、
を含む、これから本質的になる、又はこれからなる、化合物が装填されたシルク粒子、好ましくはスパイダーシルク粒子を製造する方法に関する。
アラチヌラ・ヒツギンシ(Arachnura higginsi)、アラネウス・サークリスパルサス(Araneuscirculissparsus)、ニワオニグモ、アルギオープ・ピクタ(Argiope picta)、スジコガネグモ(Banded Garden Spider)(アルギオープ・トリファシアタ(Argiopetrifasciata))、マダラジョロウグモ(Batik Golden Web Spider)(ネフィラ・アンチポディアナ(Nephila antipodiana))、ベッカリズテントスパイダー(Beccari'sTent Spider)(シルトホラ・ベッカリ(Cyrtophora beccarii))、オオトリノフンダマシ(Bird-dropping Spider)(セラエニア・エクスカバタ(Celaeniaexcavata))、トゲグモ(Black-and-WhiteSpiny Spider)(ガステラカンタ・クフリイ(Gasteracantha kuhlii))、キマダラコガネグモ(Black-and-yellow Garden Spider)(アルギオープ・アウランチア(Argiope aurantia))、ナゲナワグモ(Bolas Spider)(オルダリウス・フルカツス(Ordgarius furcatus))、イセキグモ(Bolas Spiders -Magnificent Spider)(オルガリウス・マグニフィカス(Ordgarius magnificus))、イエオニグモ(Brown Sailor Spider)(ネオスコナ・ナウチカ(Neosconanautica))、チャアシグモ(Brown-Legged Spider)(ネオスコナ・ルホフェモラタ(Neoscona rufofemorata))、キャップドブラックヘッディドスパイダー(CappedBlack-Headed Spider)(ジギエラ・カリプトラタ(Zygiella calyptrata))、ミツカドオニグモ(Common Garden Spider)(パラウィキア・デハアニ(Parawixia dehaani))、キタドヨウグモ(Common Orb Weaver)(ネオスコナ・オキサンセンシス(Neosconaoxancensis))、クラブライクスパイニーオーブウェーバー(Crab-like Spiny OrbWeaver)(ガステラカンタ・カンクリホルミス(エリプソイデス)(Gasteracanthacancriformis(elipsoides)))、オオナガトゲトゲグモ(Curved Spiny Spider)(ガステラカンタ・アルクアタ(Gasteracanthaarcuata))、シルトホラ・モルセンシス(Cyrtophora moluccensis)、シルトホラ・パルナシア(Cyrtophora parnasia)、ドロホンス・コニフェラ(Dolophonesconifera)、ドロホンス・ツリゲラ(Dolophones turrigera)、ドリアズスパイニースパイダー(Doria's Spiny Spider)(ガステラカンタ・ドリアエ(Gasteracanthadoriae))、チブサトゲグモ(Double-Spotted Spiny Spider)(ガステラカンタ・マモサ(Gasteracantha mammosa))、キヌアミグモ(Double-TailedTent Spider)(シルトホラ・エキサンテマチカ(Cyrtophora exanthematica))、アクレペリア・セロペギア(Aculeperia ceropegia)、エリオホラ・プスツロサ(Eriophorapustulosa)、フラットアネプション(Flat Anepsion)(アネプション・デプレシウム(Anepsion depressium))、フォースパインドジュエルスパイダー(Four-spinedJewel Spider)(ガステラカンタ・クアドリスピノーサ(Gasteracantha quadrispinosa))、ガーデンオーブウェブスパイダー(Garden OrbWeb Spider)(エリオホラ・トランスマリナ(Eriophora transmarina))、ジャイアントライケンオーブウェーバー(Giant Lichen Orbweaver)(アラネウス・ビセンテナリウス(Araneusbicentenarius))、ジョロウグモ(Golden Web Spider)(ネフィラ・マクラタ(Nephila maculata))、ハッセルツスパイニースパイダー(Hasselt'sSpiny Spider)(ガステラカンタ・ハッセルティ(Gasteracantha hasseltii))、テゲナリア・アトリカ(Tegenaria atrica)、ヘウロデス・ツリタ(Heurodes turrita)、アイランドサイクローサスパイダー(IslandCyclosa Spider)(サイクローサ・インスラナ(Cyclosa insulana))、ジュエルスパイダー又はスパイニースパイダー(アストラカンタ・マイナックス(Astracantha minax))、キドニーガーデンスパイダー(KidneyGarden Spider)(アラネウス・ミチフィカス(Araneus mitificus))、ラグライジズガーデンスパイダー(Laglaise's Garden Spider)(エリオビキシア・ラグライセイ(Eriovixialaglaisei))、ロングベリードサイクローサスパイダー(Long-Bellied CyclosaSpider)(サイクローサ・ビフィダ(Cyclosa bifida))、マラバルジョロウグモモドキ(Malabar Spider)(ネフィレンギス・マラバレンシス(Nephilengysmalabarensis))、マルチカラードセントアンドリュースクロススパイダー(Multi-ColouredSt Andrew's Cross Spider)(アルギオープ・ベルシカラー(Argiopeversicolor))、ケハイグモ(Ornamental Tree-Trunk Spider)(ヘレンニア・オルナチシマ(Herennia ornatissima))、ナガマルコガネグモ(Oval St.Andrew's Cross Spider)(アルギオープ・アエムラ(Argiope aemula))、ハラビロスズミグモ(Red Tent Spider)(シルトホラ・ウニカラー(Cyrtophoraunicolor))、ロシアンテントスパイダー(Russian Tent Spider)(シルトホラ・ヒルタ(Cyrtophora hirta))、カラフトオニグモ(SaintAndrew's Cross Spider)(アルギオープ・ケイセルリンギ(Argiope keyserlingi))、ハツリグモ(Scarlet Acusilas)(アクシラス・コシネウス(Acusilascoccineus))、ギンコガネグモ(Silver Argiope)(アルギオープ・アルゲンタタ(Argiope argentata))、スパイニーバックドオーブウェーバー(SpinybackedOrbweaver)(ガステラカンタ・カンクリホルミス(Gasteracantha cancriformis))、スポッテドオーブウェーバー(Spotted Orbweaver)(ネオスコナ・ドミシリオルム(Neosconadomiciliorum))、セントアンドリュースクロス(St. Andrews Cross)(アルギオープ・アエテリア(Argiope aetheria))、カラフトオニグモ(アルギオープ・ケイセルリンギ)、ゲホウグモ(Tree-Stump Spider)(ポルチス・イレピヅス(Poltys illepidus))、サンカクグモ(Triangular Spider)(アルキス・クラバツス(Arkys clavatus))、サンカクグモ(アルキス・ランセアリウス(Arkyslancearius))、フタトゲグモ(Two-spinedSpider)(ポエシロパキス・アウストララシア(Poecilopachys australasia))、ジョロウグモ種、例えばアメリカジョロウグモ、アフリカジョロウグモ(Nephila senegalensis)及びマダガスカルジョロウグモ(Nephilamadagascariensis)。スパイダーシルク配列はハイイロゴケグモ(brown widowspiders)(ラトロデクツス・ゲオメトリクス(Latrodectus geometricus))、クロゴケグモ(black widow spiders)又はハイイロゴケグモ(grey widow spiders)等のゴケグモから誘導することもできる。
a)1つ又は複数の合成反復シルクタンパク質、例えばスパイダーシルクタンパク質の配列、及び/又は
b)1つ又は複数の真の非反復シルクタンパク質、例えばスパイダーシルクタンパク質の配列
を含み得る。
モジュールA:GPYGPGASAA AAAAGGYGPG SGQQ(配列番号20)、
モジュールC:GSSAAAAAAA ASGPGGYGPE NQGPSGPGGY GPGGP(配列番号21)、
モジュールQ:GPGQQGPGQQ GPGQQGPGQQ(配列番号22)、
モジュールK:GPGGAGGPYGPGGAGGPYGPGGAGGPY(配列番号23)、
モジュールsp:GGTTIIEDLD ITIDGADGPITISEELTI(配列番号24)、
モジュールX:GGAGGAGGAG GSGGAGGS(配列番号27)及び
モジュールY:GPGGAGPGGY GPGGSGPGGY GPGGSGPGGY(配列番号28)。
モジュールAC:GPYGPGASAA AAAAGGYGPG CGQQ(配列番号29)、
モジュールAK:GPYGPGASAA AAAAGGYGPG KGQQ(配列番号30)、
モジュールCC:GSSAAAAAAA ASGPGGYGPE NQGPCGPGGY GPGGP(配列番号31)、
モジュールCK1:GSSAAAAAAA ASGPGGYGPE NQGPKGPGG Y GPGGP(配列番号32)、
モジュールCK2:GSSAAAAAAA ASGPGGYGPK NQGPSGPGGY GPGGP(配列番号33)及び
モジュールCKC:GSSAAAAAAA ASGPGGYGPK NQGPCGPGGY GPGGP(配列番号34)。
TAGCYS1:GCGGGGGGSGGGG(配列番号35)、
TAGCYS2:GCGGGGGG(配列番号36)、
TAGCYS3:GCGGSGGGGSGGGG(配列番号37)、
TAGLYS1:GKGGGGGGSGGGG(配列番号38)及び
TAGLYS2:GKGGGGGG(配列番号39)。
酸に対して:log D=log P−log(1+10pH−pKa)、及び
塩基に対して:log D=log P−log(1+10pKa-pH)。
a)少なくとも2つの同一の反復単位を含むシルクポリペプチド、好ましくはスパイダーシルクポリペプチドを1つ又は複数含む水溶液を準備する工程と、
b)該シルクポリペプチド、好ましくはスパイダーシルクポリペプチドの凝集を誘起し、シルク粒子、好ましくはスパイダーシルク粒子を形成する、誘起する工程と、
c)該シルク粒子、好ましくはスパイダーシルク粒子を相分離により分離する工程と、
により作製する。
カプセル封入効率(w/w%)=(粒子中の化合物の量/最初に添加した化合物)×100
カプセル封入効率=0.1g/0.15g=0.66=66%
例えば「装填率」は以下のデータを用いて10%と算出される:シルク粒子の表面及びマトリクスと非共有結合した化合物の量:0.1g、最初に添加した化合物の量:1.0g。
装填率=0.1g/1.0g=0.1=10%
i)GPGXX(配列番号3)(ここでXは任意のアミノ酸であり、好ましくはそれぞれの場合で独立してA、S、G、Y、P及びQからなる群から選択される)、
ii)GGX(ここでXは任意のアミノ酸であり、好ましくはそれぞれの場合で独立してY、P、R、S、A、T、N及びQからなる群から選択される)、
iii)Ax(ここでxは5〜10の整数である)
からなる群から選択されるコンセンサス配列を少なくとも1つ、好ましくは1つ含む、少なくとも2つの同一の反復単位を含む、これから本質的になる、又はこれからなる。
(i)アミノ酸配列として、好ましくはこの順番でGPGAS(配列番号5)、AAAAAA(配列番号13)、GGY及びGPGSG(配列番号6)、
(ii)アミノ酸配列として、好ましくはこの順番でAAAAAAAA(配列番号15)、GPGGY(配列番号7)、GPGGY(配列番号7)及びGPGGP(配列番号8)、
(iii)アミノ酸配列として、GPGQQ(配列番号4)、GPGQQ(配列番号4)、GPGQQ(配列番号4)及びGPGQQ(配列番号4)、
(iv)アミノ酸配列として、好ましくはこの順番でGPGGA(配列番号9)、GGP、GPGGA(配列番号9)、GGP、GPGGA(配列番号9)及びGGP、
(v)アミノ酸配列として、好ましくはこの順番でAAAAAAAA(配列番号15)、GPGQG(配列番号40)及びGGR、
(vi)アミノ酸配列として、好ましくはこの順番でAAAAAAAA(配列番号15)、GPGGG(配列番号10)、GGR、GGN及びGGR、
(vii)アミノ酸配列として、好ましくはこの順番でGGA、GGA、GGA、GGS、GGA及びGGS、並びに/又は
(viii)アミノ酸配列として、好ましくはこの順番でGPGGA(配列番号9)、GPGGY(配列番号7)、GPGGS(配列番号11)、GPGGY(配列番号7)、GPGGS(配列番号11)及びGPGGY(配列番号7)
を含むか又はこれからなる反復単位を含む、これから本質的になる、又はこれからなる。
i)GPGXX(配列番号3)(ここでXは任意のアミノ酸であり、好ましくはそれぞれの場合で独立してA、S、G、Y、P及びQからなる群から選択される)、
ii)GGX(ここでXは任意のアミノ酸であり、好ましくはそれぞれの場合で独立してY、P、R、S、A、T、N及びQから選択され、より好ましくはそれぞれの場合で独立してY、P及びQから選択される)、及び
iii)Ax(ここでxは5〜10の整数である)
からなる群から選択されるコンセンサス配列を少なくとも1つ、好ましくは1つ含む。上で言及されたように、本発明によるシルクポリペプチドに含まれる反復単位のうち少なくとも2つが同一の反復単位である。
(i)アミノ酸配列として、好ましくはこの順番でGPGAS(配列番号5)、AAAAAA(配列番号13)、GGY及びGPGSG(配列番号6)を含む又はこれからなる反復単位、
(ii)アミノ酸配列として、好ましくはこの順番でAAAAAAAA(配列番号15)、GPGGY(配列番号7)、GPGGY(配列番号7)及びGPGGP(配列番号8)を含む又はこれからなる反復単位、
(iii)アミノ酸配列として、GPGQQ(配列番号4)、GPGQQ(配列番号4)、GPGQQ(配列番号4)及びGPGQQ(配列番号4)を含む又はこれからなる反復単位、
(iv)アミノ酸配列として、好ましくはこの順番でGPGGA(配列番号9)、GGP、GPGGA(配列番号9)、GGP、GPGGA(配列番号9)及びGGPを含む又はこれからなる反復単位、
(v)アミノ酸配列として、好ましくはこの順番でAAAAAAAA(配列番号15)、GPGQG(配列番号40)及びGGRを含む又はこれからなる反復単位、
(vi)アミノ酸配列として、好ましくはこの順番でAAAAAAAA(配列番号15)、GPGGG(配列番号10)、GGR、GGN及びGGRを含む又はこれからなる反復単位、
(vii)アミノ酸配列として、好ましくはこの順番でGGA、GGA、GGA、GGS、GGA及びGGSを含む又はこれからなる反復単位、並びに/又は
(viii)アミノ酸配列として、好ましくはこの順番でGPGGA(配列番号9)、GPGGY(配列番号7)、GPGGS(配列番号11)、GPGGY(配列番号7)、GPGGS(配列番号11)及びGPGGY(配列番号7)を含む又はこれからなる反復単位
を含む、これから本質的になる、又はこれからなる。
(i)反復単位として(GPGXX)n(配列番号3)(ここでXは任意のアミノ酸であり、好ましくはそれぞれの場合で独立してA、S、G、Y、P及びQから選択され、nは2、3、4、5、6、7、8又は9である)、
ii)反復単位として(GGX)n(ここでXは任意のアミノ酸であり、好ましくはそれぞれの場合で独立してY、P、R、S、A、T、N及びQから選択され、より好ましくはそれぞれの場合で独立してY、P及びQから選択され、nは2、3、4、5、6、7又は8である)、及び/又は
iii)反復単位として(Ax)n(ここでxは5〜10の整数であり、nは2、3、4、5、6、7、8、9又は10である)
を含む、これから本質的になる、又はこれからなる。上述のように、本発明によるシルクポリペプチドに含まれる反復単位のうち少なくとも2つは同一の反復単位である。
(i)式(C)mでは、配列番号21によるアミノ酸配列で表される、数「m」のCモジュール、すなわち8個〜48個のCモジュールが互いに組み合わせられ、
(ii)式(C)mNRzでは、配列番号21によるアミノ酸配列で表される、数「m」のCモジュール、すなわち8個〜48個のCモジュールが互いに組み合わせられ、上記Cモジュールはさらに、数「z」の非反復(NR)単位、すなわち1個〜3個の非反復(NR)単位、例えば配列番号41によるアミノ酸配列で表される非反復(NR)単位NR3又は配列番号42によるアミノ酸配列で表される非反復(NR)単位NR4と組み合わせられ、
(iii)式NRz(C)mでは、数「z」の非反復(NR)単位、すなわち1個〜3個の非反復(NR)単位、例えば配列番号41によるアミノ酸配列で表される非反復(NR)単位NR3又は配列番号42によるアミノ酸配列で表される非反復(NR)単位NR4が存在し(z=1)、又は互いに組み合わせられ(z=2又は3)、上記非反復(NR)単位(複数も可)はさらに、配列番号21によるアミノ酸配列で表される、数「m」のCモジュール、すなわち8個〜48個のCモジュールと組み合わせられ、
(iv)式(AQ)nでは、数「n」のAモジュールとQモジュールとの組み合わせ、すなわち6個〜24個のAモジュールとQモジュールとの組み合わせ(ここでモジュールAは配列番号20によるアミノ酸配列により表され、モジュールQは配列番号22によるアミノ酸配列により表される)が互いに組み合わされ、
(v)式(AQ)nNRzでは、数「n」のAモジュールとQモジュールとの組み合わせ、すなわち6個〜24個のAモジュールとQモジュールとの組み合わせ(ここでモジュールAは配列番号20によるアミノ酸配列により表され、モジュールQは配列番号22によるアミノ酸配列により表される)が互いに組み合わされ、上記AモジュールとQモジュールとの組み合わせはさらに、数「z」の非反復(NR)単位、すなわち1個〜3個の非反復(NR)単位、例えば配列番号41によるアミノ酸配列で表される非反復(NR)単位NR3又は配列番号42によるアミノ酸配列で表される非反復(NR)単位NR4と組み合わせられ、
(vi)式NRz(AQ)nでは、数「z」の非反復(NR)単位、すなわち1個〜3個の非反復(NR)単位、例えば配列番号41によるアミノ酸配列で表される非反復(NR)単位NR3又は配列番号42によるアミノ酸配列で表される非反復(NR)単位NR4が存在し(z=1)、又は互いに組み合わせられ(z=2又は3)、上記非反復(NR)単位(複数も可)はさらに、数「n」のAモジュールとQモジュールとの組み合わせ、すなわち6個〜24個のAモジュールとQモジュールとの組み合わせ(ここでモジュールAは配列番号20によるアミノ酸配列により表され、モジュールQは配列番号22によるアミノ酸配列により表される)と組み合わせられ、
(vii)式(QAQ)oでは、数「o」のQモジュールと、Aモジュールと、Qモジュールとの組み合わせ、すなわち8個〜16個のQモジュールと、Aモジュールと、Qモジュールとの組み合わせ(ここでモジュールQは配列番号22によるアミノ酸配列で表され、モジュールAは配列番号20によるアミノ酸配列で表される)が互いに組み合わされ、
(viii)式(QAQ)oNRzでは、数「o」のQモジュールと、Aモジュールと、Qモジュールとの組み合わせ、すなわち8個〜16個のQモジュールと、Aモジュールと、Qモジュールとの組み合わせ(ここでモジュールQは配列番号22によるアミノ酸配列で表され、モジュールAは配列番号20によるアミノ酸配列で表される)が互いに組み合わされ、上記Qモジュールと、Aモジュールと、Qモジュールとの組み合わせはさらに、数「z」の非反復(NR)単位、すなわち1個〜3個の非反復(NR)単位、例えば配列番号41によるアミノ酸配列で表される非反復(NR)単位NR3又は配列番号42によるアミノ酸配列で表される非反復(NR)単位NR4と組み合わせられ、
(ix)式NRz(QAQ)oでは、数「z」の非反復(NR)単位、すなわち1個〜3個の非反復(NR)単位、例えば配列番号41によるアミノ酸配列で表される非反復(NR)単位NR3又は配列番号42によるアミノ酸配列で表される非反復(NR)単位NR4が存在し(z=1)、又は互いに組み合わせられ(z=2又は3)、上記非反復(NR)単位(複数も可)はさらに、数「o」のQモジュールと、Aモジュールと、Qモジュールとの組み合わせ、すなわち8個〜16個のQモジュールと、Aモジュールと、Qモジュールとの組み合わせ(ここでモジュールQは配列番号22によるアミノ酸配列で表され、モジュールAは配列番号20によるアミノ酸配列で表される)と組み合わせられ、
(x)式Ypでは、配列番号28によるアミノ酸配列で表される、数「p」のYモジュール、すなわち8個〜16個のYモジュールが互いに組み合わされ、
(xi)式Xpでは、配列番号27によるアミノ酸配列で表される、数「p」のXモジュール、すなわち8個〜16個のXモジュールが互いに組み合わされ、
(xii)式Kpでは、配列番号23によるアミノ酸配列で表される、数「p」のKモジュール、すなわち8個〜16個のKモジュールが互いに組み合わされる。
i)GPGXX(配列番号3)(ここでXは任意のアミノ酸であり、好ましくはそれぞれの場合で独立してA、S、G、Y、P及びQからなる群から選択される)、
ii)GGX(ここでXは任意のアミノ酸であり、好ましくはそれぞれの場合で独立してY、P、R、S、A、T、N及びQからなる群から選択される)、
iii)Ax(ここでxは5〜10の整数である)
からなる群から選択されるコンセンサス配列を少なくとも1つ、好ましくは1つ含む少なくとも2つの同一の反復単位を含む、これから本質的になる、又はこれからなる。
i)GPGXX(配列番号3)(ここでXは任意のアミノ酸であり、好ましくはそれぞれの場合で独立してA、S、G、Y、P及びQからなる群から選択される)、
ii)GGX(ここでXは任意のアミノ酸であり、好ましくはそれぞれの場合で独立してY、P、R、S、A、T、N及びQ、より好ましくはそれぞれの場合で独立してY、P及びQからなる群から選択される)、及び
iii)Ax(ここでxは5〜10の整数である)
からなる群から選択されるコンセンサス配列を少なくとも1つ、好ましくは1つ含む、2個〜80個の反復単位、3個〜80個の反復単位若しくは4個〜60個の反復単位、より好ましくは8個〜48個の反復単位、又は10個〜40個の反復単位、最も好ましくは16個〜32個の反復単位、すなわち2個、3個、4個、5個、6個、7個、8個、9個、10個、11個、12個、13個、14個、15個、16個、17個、18個、19個、20個、21個、22個、23個、24個、25個、26個、27個、28個、29個、30個、31個、32個、33個、34個、35個、36個、37個、38個、39個、40個、41個、42個、43個、44個、45個、46個、47個、48個、49個、50個、51個、52個、53個、54個、55個、56個、57個、58個、59個、60個、61個、62個、63個、64個、65個、66個、67個、68個、69個、70個、71個、72個、73個、74個、75個、76個、77個、78個、79個又は80個の反復単位を含む、これから本質的になる、又はこれからなる。
eADF4(C16)のアミノ酸配列を、ニワオニグモ由来のADF4の天然配列から適合させた。eADF4(C16)タンパク質を、単一モチーフの組み合わせ及び多量体化によって改変した。得られるeADF4(C16)は、アミノ酸配列GSSAAAAAAAASGPGGYGPENQGPSGPGGYGPGGP(配列番号21)を有するモジュールCの反復単位を16個含む。得られるタンパク質は、48kDaの分子質量を有する。タンパク質を、過去に記載された(Hummerichet al., 2004)ように精製し、98%を超える純度を有するものとした。そのアミノ酸組成のために、eADF4(C16)は、3.48という理論的等電点を有し、生理学的pH(7.4)で正味の負電荷を示す。
全ての薬物を、0.21μmol/mlの濃度で水に溶解した。薬物物質及びそれらの特徴的な特性を、表1に示す。主要な選択基準は、水性媒体における溶解度(オクタノール/水分配係数(log P)によって表現される)、酸性解離定数(プロトン化塩基(BH+)又は酸(HA)についてのpKa)、及び得られる水性媒体における正味電荷(優勢な又は永久的な電荷)とした。
表中の英語:
Model drug:モデル薬物
Molecular weight:分子量
Dissociation constant of BH+:BH+の解離定数
Dissociation constant of HA:HAの解離定数
Predominant change at pH7:pH7で優勢な電荷
Permanently charged:永久的に荷電している
Phenol red:フェノールレッド
Tetracaine HCl:テトラカインHCl
Procaine HCl:プロカインHCl
Papaverine HCl:パパベリンHCl
Ephedrine HCl:エフェドリンHCl
Propranol HCl:プロプラノロールHCl
Ethacridine lactate:乳酸エタクリジン
Methyl violet:メチルバイオレット
negative:負
positive:正
yes:はい
no:いいえ
凍結乾燥されているタンパク質eADF4(C16)を、6Mのグアニジウムチオシアネートに溶解した。透析を、4℃で、6000Da〜8000Daの分子量カットオフ値を有する膜(Spectrum Laboratories、Rancho Dominguez, USA)を使用して、10mMのトリス(ヒドロキシメチル)アミノメタン−(Tris)/HCl(pH8)に対して行った。eADF4(C16)溶液の濃度を、20℃で、Cary100分光光度計(Varian Medical Systems、Palo Alto, USA)、及び276nmでのeADF4(C16)のモル吸光係数(ε=46400M−1cm−1)を使用して、UV−Vis分光分析によって決定した。eADF4(C16)粒子を、Slotta et al. (2008)にて過去に記載されたような相分離手順を使用して調製した。eADF4(C16)水溶液(c=1.0mg/ml)を、ピペットを使用して、リン酸カリウム(2M、pH8)と1:10の体積比で混合した。得られた粒子を、10000×gで10分間遠心分離し、精製水で3回洗浄した。得られた粒子を水に再分散させ、粒子濃度(mg/ml単位での粒子数)を重量測定法によって決定した。既知のタンパク質粒子濃度のストック分散液を、全ての実験について使用した。
懸濁液中のeADF4(C16)粒子のコロイド安定性を、種々の濃度(0M〜2.0M)の(NH4)2SO4溶液1.0mlに粒子1.0mgを添加し、15分後に波長400nmで散乱光の強度を測定することによって研究した。Mie理論に基づくと、順方向での散乱光の強度は、粒径が増大するにつれて増大する。したがって、希釈分散液中での電解質に誘導されるフロキュレーションの開始は、順方向での散乱光の強度の増大によって検出することができる。
現行の技術水準の以下の方法を使用して、本発明によるスパイダーシルク粒子を特性化することができる:
eADF4(C16)粒子を、Thermanoxプラスチックカバースリップ(Nagle Nunc、USA)上に固定化し、室温で乾燥させ、真空下で金スパッタリングし、JSM 5900 LV走査電子顕微鏡(JEOL Ltd.、日本)(20kVで)を用いて分析した。
粒径及びサイズ分布を、レーザー回折分光分析(株式会社堀場製作所、Partica LA−950、日本)を使用して三連で決定した。水について1.33、及びタンパク質について1.60という屈折率を、粒径の計算のために採用した。濃度の効果を排除するために、全ての試料を、82%の透過率をもたらす等濃度で測定した。加えて、各調製物の乾燥標本を、走査電子顕微鏡検査(SEM)によって分析して、球の形状及び球のサイズを確認した。
フーリエ変換赤外(FTIR)スペクトルを、Bruker Equinox 55 FTIR分光計を使用して収集した。試料を、CaF2ディスク上にeADF4(C16)粒子懸濁液の液滴を落とし、その後風乾することによって調製した。吸光スペクトルを、4cm−1の分解能で非偏光を用いて400cm−1〜4000cm−1の間で記録した。測定を25℃及び相対湿度30%で実施し、各スペクトルを32回蓄積した。eADF4(C16)粒子の二次構造を、アミドIバンド(1600cm−1〜1700cm−1)を使用して分析した。1648cm−1〜1660cm−1、1625cm−1〜1640cm−1及び1660cm−1〜1668cm−1のピークを、それぞれαヘリックス構造、βシート構造及びβターン構造に割り当てることができる。
Cary100分光光度計(Varian Medical Systems、Palo Alto, USA)を使用する紫外−可視分光分析を、装填効率及び放出挙動の算出の基礎としての上清中の薬物濃度の決定のために利用した。全てのモデル薬物に関する較正曲線を、全てのストック溶液について5つの異なる濃度を使用することによって取得した。
モデル薬物によるeADF4(C16)粒子の装填メカニズムを解明及び特性化するために、ゼータ電位測定を、添加したモデル薬物の量に応じて行った。ゼータ電位を、Nanoseries Malvern Zetasizer(Malvern、Worcestershire, UK)を使用して決定した。自動滴定を、Malvern Multipurpose Titrator MPT−2を用いて行った。実験を、25℃で蒸留水(pH7)中で行った。各測定を、三連で行った。
スパイダーシルク粒子の薬物装填を、以下のとおりに行った:21nmolのシルクタンパク質を含有する100μlのスパイダーシルク粒子懸濁液を、0.21μmolのモデル薬物を含有する1.0mlのモデル薬物溶液と混合した。室温で10分のインキュベーションの後、試料を10000gで10分間遠心分離し、上清をUV−Vis分光分析を使用して残留薬物濃度に関して分析した。モデル薬物に関する標準的な較正曲線を、薬物の定量化のために使用した。1.0mlのモデル薬物溶液と混合した100μlの水のみを含有する試料の対照群を、各実験に対して調製した。対照及び試料の上清由来の薬物濃度を使用して、スパイダーシルク粒子中に取り込まれた薬物の量を算出した。全ての実験を三連で行った。カプセル封入効率及び装填率を、それぞれ式(1)及び式(2)を使用することによって決定した:
(1)カプセル封入効率(w/w%)=(粒子中のモデル薬物の量/最初に添加したモデル薬物)×100
(2)装填率(w/w%)=(粒子中のモデル薬物の量/粒子の量)×100
pH7でのその負電荷のために、eADF4(C16)は、静電相互作用に基づき、正に荷電した分子と複合体を形成することができる。小分子が粒子表面に結合するか、又はその内部に浸透することができるかを解明するために、高密度ガラスマトリクス中への薬物分子の浸透プロセスは起こり得ないと仮定して、ガラスビーズの装填効率をeADF4(C16)粒子の装填効率と比較した。ガラスビーズの高い負のゼータ電位(≒−50mV)のために、タンパク質マトリクス中への拡散が起こらない場合、ガラスビーズの装填効率は、スパイダーシルク粒子(ゼータ電位≒−22mV)の装填効率よりも高いものとする。
(3)酸に対して:log D=log P−log(1+10pH−pKa)
(4)塩基に対して:log D=log P−log(1+10pKa−pH)
Model drug:モデル薬物
Chemical nature:化学的性質
Maximal drug content:最大薬物含有量
Expeimental drug content:実験的薬物含有量
Encapsulation efficiency:カプセル封入効率
Ephedrine HCl:エフェドリンHCl
Procaine HCl:プロカインHCl
Propranol HCl:ププロプラノロールHCl
Papaverine HCl:パパベリンHCl
Tetracaine HCl:テトラカインHCl
Ethacridine lactate:乳酸エタクリジン
Phenol red:フェノールレッド
Methyl violet:メチルバイオレット
base:塩基
strong base:強塩基
strong acid:強酸
薬物を装填したeADF4(C16)粒子を、蒸留水で洗浄し、1mlのPBS(pH7.4)に懸濁した後、絶えず振とうしながら37℃でインキュベーションした。各バイアルは、4.2μmolのスパイダーシルクタンパク質を含有する2mgの薬物を装填した粒子を含有するものとした。溶媒を、各試料から定期的に取り除き、新たなPBS(pH7.4)と交換した。その後、媒体中の薬物含有量を、UV−Vis分光分析を使用して分析した。累積的なモデル薬物放出の百分率(%w/w)を、インキュベーション時間に応じて調査した。各実験を三連で行った。薬物を装填したeADF4(C16)粒子の放出挙動に対する種々のpH値の効果を研究するために、1mgの薬物を装填したシルク粒子を、5つの異なるpH値(pH2、pH4、pH6、pH7.4及びpH8.8)の1.0mlのPBS中で5日間インキュベートした。溶媒を毎日抜き取り、粒子を新たな媒体に再分散させた。抜き取った試料の上清を、UV−Vis分光分析を用いて、薬物含有量決定のために分析した。
Model drug:モデル薬物
time(d):時間(日)
Release:放出
Methyl violet:メチルバイオレット
Ethacridine lactate:乳酸エタクリジン
eADF4(C16)シルク粒子の分解性を分析するために、エラスターゼ及びトリプシン(両方とも、脊椎動物における自然発生的なプロテアーゼ)の混合物を使用した。1.0mgのシルク粒子を、0.8μgのエラスターゼ及び12.5μgのトリプシンの存在下で、1.0mlのPBS中でインキュベートした。2週間にわたり、試料を、毎日採取し、遠心分離した。レーザー回折分光分析及び走査電子顕微鏡検査を使用するサイズ及び形態の更なる分析のために、eADF4(C16)粒子を含有するペレットを、蒸留水に再分散させ、3回洗浄した。ブタ膵臓由来のエラスターゼ及びトリプシンは、Sigma Aldrich(St. Louis, USA)によって供給されたものである。
装填実験のために、以下のタンパク質化合物を選んだ:
(a)11.35という等電点を有するタンパク質化合物であるリゾチーム。このタンパク質は、調査したpH(7.0)で全体として正の正味電荷を示し、14.3kDaの分子量を有する。
(b)神経成長因子(NGF)は、9.5という等電点及び13kDaの分子量を有する。NGFも、調査したpH(7.0)で正に荷電している。
Quantity 量
Particle size 粒径
Intensity at400 nm 400nmでの強度
Concentration 濃度
図2の英語訳
ζ-Potential ζ電位
Methyl violet メチルバイオレット
Glass beads ガラスビーズ
Particles 粒子
Loading 装填率
Molar ratio モル比
Loadingefficiency 装填効率
図3の英語訳
Loadingefficiency 装填効率
図4の英語訳
Release 放出率
time 時間
Ethacridinelactate 乳酸エタクリジン
Methyl violet メチルバイオレット
(theo.) 理論
(exp.) 実験
図5の英語訳
time 時間
size サイズ
mean ofparticle ensemble 粒子集合体の平均
mode ofparticle ensemble 粒子集合体の最頻値
particles 粒子
agglomerations 凝集体
Intensity 強度
wavenumber 波数
control 対照
day 日目
図6の英語訳
loading 装填率
w/w-ratio w/w比
loadingefficiency 装填効率
zeta-potential ゼータ電位
blank ブランク
loaded eADF4(C16) particles at pH 7.0/30mM pH7.0/30mMで装填されたeADF4(C16)粒子
図7の英語訳
loading 装填率
w/w-ratio w/w比
loadingefficiency 装填効率
図8の英語訳
Z-average Z平均
blank ブランク
lysozyme リゾチーム
配列番号3、20〜24、27〜34、45〜96:
配列番号3 GPGXX; X= A, S, G, Y, P, Q
配列番号20 モジュールA:GPYGPGASAA AAAAGGYGPGSGQQ
配列番号21 モジュールC:GSSAAAAAAA ASGPGGYGPE NQGPSGPGGY GPGGP
配列番号22 モジュールQ:GPGQQGPGQQ GPGQQGPGQQ
配列番号23 モジュールK:GPGGAGGPYGPGGAGGPYGPGGAGGPY
配列番号24 モジュールsp:GGTTIIEDLD ITIDGADGPITISEELTI
配列番号27 モジュールX:GGAGGAGGAG GSGGAGGS
配列番号28 モジュールY:GPGGAGPGGY GPGGSGPGGY GPGGSGPGGY
配列番号29 モジュールAC:GPYGPGASAA AAAAGGYGPG CGQQ
配列番号30 モジュールAK:GPYGPGASAA AAAAGGYGPG KGQQ
配列番号31 モジュールCC:GSSAAAAAAA ASGPGGYGPE NQGPCGPGGY GPGGP
配列番号32 モジュールCK1:GSSAAAAAAA ASGPGGYGPE NQGPKGPGG Y GPGGP
配列番号33 モジュールCK2:GSSAAAAAAA ASGPGGYGPK NQGPSGPGGY GPGGP
配列番号34 モジュールCKC:GSSAAAAAAA ASGPGGYGPK NQGPCGPGGY GPGGP
配列番号45 − NR3(ADF−3):
MASMTGGQQMGRGSMGAASAAVSVGGYGPQSSSAPVASAAASRLSSPAASSRVSSAVSSLVSSGPTNQAALSNTISSVVSQVSASNPGLSGCDVLVQALLEVVSALVSILGSSSIGQINYGASAQYTQMVGQSVAQALAG
配列番号46 − NR4(ADF−4):
MASMTGGQQMGRGSMGAYGPSPSASASVAASRLSSPAASSRVSSAVSSLVSSGPTNGAAVSGALNSLVSQISASNPGLSGCDALVQALLELVSALVALLSSASIGQVNVSSVSQSTQMISQALSG
配列番号47 − ADF−3:
MASMTGGQQMGRDPNSARAGSGQQGPGQQGPGQQGPGQQGPYGPGASAAAAAAGGYGPGSGQQGPSQQGPGQQGPGGQGPYGPGASAAAAAAGGYGPGSGQQGPGGQGPYGGSSAAAAAAGGNGPGSGQQGPGQQGPGQQGPGASAAAAAAGGYGPGSGQQGPGQQGPGGQGPYGPGASAAAAAAGGYGPGSGQQGPGQQGPGGQGPYGPGASAAAAAAGGYGPGSGQQGPGQQGPGQQGPGGQGPYGPGASAAAAAAGGYGPGYGQQGPGQQGPGGQGPYGPGASAASAASGGYGPGSGQQGPGQQGPGGQGPYGPGASAAAAAAGGYGPGSGQQGPGQQGPGQQGPGQQGPGGQGPYGPGASAAAAAAGGYGPGSGQQGPGQQGPGQQGPGQQGPGQQGPGQQGPGQQGPGQQGPGQQGPGGQGAYGPGASAAAGAAGGYGPGSGQQGPGQQGPGQQGPGQQGPGQQGPGQQGPGQQGPGQQGPYGPGASAAAAAAGGYGPGSGQQGPGQQGPGQQGPVGQGPYGPGAASAAVSVGGYGPQSSSAPVASAAASRLSSPAASSRVSSAVSSLVSSGPTNQAALSNTISSVVSQVSASNPGLSGCDVLVQALLEVVSALVSILGSSSIGQINYGASAQYTQMVGQSVAQALA
配列番号48 − ADF−4:
MASMTGGQQMGRAARAGSSAAAAAAASGSGGYGPENQGPSGPVAYGPGGPVSSAAAAAAAGSGPGGYGPENQGPSGPGGYGPGGSGSSAAAAAAAASGPGGYGPGSQGPSGPGGSGGYGPGSQGPSGPGASSAAAAAAAASGPGGYGPGSQGPSGPGAYGPGGPGSSAAASGPGGYGPGSQGPSGPGGSGGYGPGSQGPSGPGGPGASAAAAAAAAASGPGGYGPGSQGPSGPGAYGPGGPGSSAAASGPGGYGPGSQGPSGPGAYGPGGPGSSAAAAAAAGSGPGGYGPGNQGPSGPGGYGPGGPGSSAAAAAAASGPGGYGPGSQGPSGPGVYGPGGPGSSAAAAAAAGSGPGGYGPGNQGPSGPGGYGPGGSGSSAAAAAAAASGPGGYGPGSQGPSGPGGSGGYGPGSQGPSGPGASSAAAAAAAASGPGGYGPGSQGPSGPGAYGPGGPGSSAAASGPGGYGPGSQGPSGPGAYGPGGPGSSAAAAAAASGPGGYGPGSQGPSGPGGSRGYGPGSQGPGGPGASAAAAAAAAASGPGGYGPGSQGPSGPGYQGPSGPGAYGPSPSASASVAASRLSSPAASSRVSSAVSSLVSSGPTNGAAVSGALNSLVSQISASNPGLSGCDALVQALLELVSALVAILSSASIGQVNVSSVSQSTQMISQALSG
ニワオニグモフィブロイン
配列番号49:
>gi|1263283|gb|AAC47008.1|フィブロイン−1
HESSYAAAMAASTRNSDFIRNMSYQMGRLLSNAGAITESTASSAASSASSTVTESIRTYGPAAIFSGAGAGAGVGVGGAGGYGQGYGAGAGAGAGAGAGAGGAGGYGQGYGAGAAAAAGAGAGAAGGYGGGSGAGAGGAGGYGQGYGAGSGAGAGAAAAAGASAGAAGGYGGGAGVGAGAGAGAAGGYGQSYGSGAGAGAGAGAAAAAGAGARAAGGYGGGYGAGAGAGAGAAASAGASGGYGGGYGGGAGAGAVAGASAGSYGGAVNRLSSAGAASRVSSNVAAIASAGAAALPNVISNIYSGVLSSGVSSSEALIQALLEVISALIHVLGSASIGNVSSVGVNSALNAVQNAVGAYAG
配列番号50:
>gi|1263285|gb|AAC47009.1|フィブロイン−2
GSQGAGGAGQGGYGAGGGGAAAAAAAAVGAGGGGQGGLGSGGAGQGYGAGLGGQGGASAAAAAAGGQGGQGGQGGYGGLGSQGAGGAGQLGYGAGQESAAAAAAAAGGAGGGGQGGLGAGGAGQGYGAAGLGGQGGAGQGGGSGAAAAAGGQGGQGGYGGLGPQGAGGAGQGGYGGGSLQYGGQGQAQAAAASAAASRLSSPSAAARVSSAVSLVSNGGPTSPAALSSSISNVVSQISASNPGLSGCDILVQALLEIISALVHILGSANIGPVNSSSAGQ
SASIVGQSVYRALS
配列番号51:
>gi|1263287|gb|AAC47010.1|フィブロイン−3
ARAGSGQQGPGQQGPGQQGPGQQGPYGPGASAAAAAAGGYGPGSGQQGPSQQGPGQQGPGGQGPYGPGASAAAAAAGGYGPGSGQQGPGGQGPYGPGSSAAAAAAGGNGPGSGQQGAGQQGPGQQGPGASAAAAAAGGYGPGSGQQGPGQQGPGGQGPYGPGASAAAAAAGGYGPGSGQGPGQQGPGGQGPYGPGASAAAAAAGGYGPGSGQQGPGQQGPGQQGPGGQGPYGPGASAAAAAAGGYGPGYGQQGPGQQGPGGQGPYGPGASAASAASGGYGPGSGQQGPGQQGPGGQGPYGPGASAAAAAAGGYGPGSGQQGPGQQGPGQQGPGQQGPGGQGPYGPGASAAAAAAGGYGPGSGQQGPGQQGPGQQGPGQQGPGQQGPGQQGPGQQGPGQQGPGQQGPGGQGAYGPGASAAAGAAGGYGPGSGQQGPGQQGPGQQGPGQQGPGQQGPGQQGPGQQGPGQQGPYGPGASAAAAAAGGYGPGSG
QQGPGQQGPGQQGPGGQGPYGPGAASAAVSVGGYGPQSSSVPVASAVASRLSSPAASSRVSSAVSSLVSSGPTKHAALSNTISSVVSQVSASNPGLSGCDVLVQALLEVVSALVSILGSSSIGQINYGASAQYTQMVGQSVAQALA
配列番号52:
>gi|1263289|gb|AAC47011.1|フィブロイン−4
AGSSAAAAAAASGSGGYGPENQGPSGPVAYGPGGPVSSAAAAAAAGSGPGGYGPENQGPSGPGGYGPGGSGSSAAAAAAAASGPGGYGPGSQGPSGPGGSGGYGPGSQGASGPGGPGASAAAAAAAAAASGPGGYGPGSQGPSGPGAYGPGGPGSSAAAAAAAASGPGGYGPGSQGPSGPGVYGPGGPGSSAAAAAAAGSGPGGYGPENQGPSGPGGYGPGGSGSSAAAAAAAASGPGGYGPGSQGPSGPGGSGGYGPGSQGGSGPGASAAAAAAAASGPGGYGPGSQGPSGPGYQGPSGPGAYGPSPSASASVAASVYLRLQPRLEVSSAVSSLVSSGPTNGAAVSGALNSLVSQISASNPGLSGCDALVQALLELVSALVAILSSASIGQVNVSSVSQSTQMISQALS
大瓶状腺スピドロイン1
配列番号53:
>gi|185179256|gb|ACC77633.1|大瓶状腺スピドロイン1(アメリカジョロウグモ)
AGQGGLGGQGAGQGAGAAAAAAGGAGQGGYGGLGSQGAGRGGLGGQGAGAAAAAAGGAGQGGYGGLGGQGAGQGAGQGGYGGLGSQGAGRGGQGAGAAAAAAGGAGQGGYGGLGGQGVGRGGLGGQGAAAAGGAGQGGYGGVGSGASAASAAASRLSSPQASSRVSSAVSNLVASGPTNSAALSSTISNVVSQIGASNPGLSGCDVLIQALLEVVSALIHILGSSSIGQVNYGSAGQATQIVGQSVYQALG
配列番号54:
>gi|50363145|gb|AAT75312.1|大瓶状腺スピドロイン1(アメリカジョロウグモ)
GGQGAGRGAGAAAAAAGGAGQGGYGGLGGQGAGQGAGAAAAAAGGAGQGGYGGLGSQGAGRGGYGGQGAEAAAAAAAGGAAQGGQGLGGQGAAAAAGGAGQGGFGGLGGQGAGAAAAAAGGAGQGGYGGLGSQGAGRGAGAAAAAAGGAGQGGYGGLGGQGAGRGAGAAAAAAGGAAQGGYGDLGSQGAGAAAAAAGSAGQGGYGGLGGQGAGQGAGAAAAAAGSAGQGGLGGRAGQGAGAASAAAGGAGQGGYGGLGGQGAGQGGYGGVGSGASAASSAASRLSSPEASSRVSSAVSNLVSSGPTNSAALSSTISNVVSQIGASNPGLSGCDVLVQALLEVVSALIHILGSSSIGQVNYGSAGQATQIVGQSIYQALG
配列番号55:
>gi|50363143|gb|AAT75311.1|大瓶状腺スピドロイン1(アメリカジョロウグモ)
AGAAAAAGSAGQGGYGGQGAGQGGYGGLGSQGAGRGGLGGQGAGAAAAAAAGGAGQGGLGGQGAGQGAGAAAAAAGGAGQGGYGGLGNQGAGRGGQGAAAAAAGGAGQGGYGGLGSQGAGRGGLGGQGAGAAAAAAGGAGQGGYGGLGGQGAGQGGYGGLGSQGSGRGGLGGQGAGAAAAAAGGAGQGGLGGQGAGQGAGAAAAAAGGVRQGGYGGLGSQGAGRGGQGAGAAAAAAGGAGQGGYGGLGGQGVGRGGLGGQGAGAAAAGGAGQGGYGGVGSGASAASAAASRLSSPQASSRVSSAVSNLVASGPTNSAALSSTISNVVSQIGASNPGLSGCDVLIQALLEVVSALIHILGSSSIGQVNYGSAGQATQIVGQSVYQALG
配列番号56:
>gi|50363141|gb|AAT75310.1|大瓶状腺スピドロイン1(アメリカジョロウグモ)
GGLGIQGSGRGGLGGQGAVAAAAAAAGGAVQVVLGGQGAGQGAGAAAAAAGGAGQGGYGGLGSQGAGRGGQGAGARTAAAVGAGQGGYGGQGAGQGGYGGLGSQGAGRGGLGGQGAGAAAAAAAGSAEQGLGGQGAGQGAGAAAAAAGGAGQGGYGGLGSQGAGRGGLGGQGAGAAAAAAGGAGQGGYGGLGGQGAGQGGYGGLGSQGSGRGGLGGQGAGAAAAAAGGAGQGGLGGQGAGQGAGAAAAAAGGVRQGGYGGLGSQGAGRGGQGAGAAAAAAGGAGQGGYGGLGGQGVGRGGLGGQGAGAAAAGGAGQGGYGGVGSGASAASAAASRLSSPQASSRVSSAVSNLVASGPTNSAALSSTISNVVSQIGASNPGLSGCDVLIQALLEVVSALIHILGSSSIGQVNYGSAGQATQIVGQSVYQALG
配列番号57:
>gi|50363139|gb|AAT75309.1|大瓶状腺スピドロイン1(アメリカジョロウグモ)
QGTDAAAAAAGGAGQGGYGGLGGQGAGQGGYGGLGSQGSGRGGLGGQGAGAAAAAAGGAGQGAGQGAGAAAAAAGGVRQGGYGGLGSQGAGRGGQGAGAAAAAAGGAGQGGYGGLGGQGVGRGGLGGQGAGAAAAGGAGQGGYGGVGSGASAASAAASRLSSPQASSRVSSAVSNLVASGPTNSAALSSTISNVVSQIGSSNPGLSGCDVLIQALLEVVSALIQILGSSSIGQVNYGSAGQATQIVGQSVYQALG
配列番号58:
>gi|50363137|gb|AAT75308.1|大瓶状腺スピドロイン1(アメリカジョロウグモ)
GQGAGQGAGAAAAAAGGAGQGGYGGLGNQGAGRGGQGAAAAAAGGAGQGGYGGLGSQGAGRGGLGGQGAGAAAAAAGGAGQGGYGGLGGQGAGQGAGQGGYGGLGIQGSGRGGLGGQGAGAAAAAAGGAGQGGLGGQGAGQGAGAAAAAAGGVRQGGYGGLGSQGAGRGGQGAGAAAAAAGGAGQGGYGGLGGQGVGRGGLGGQGAGAAAAGGAGQGGYGGVGSGASAASAAASRLSSPQASSRVSSAVSNLVASGPTNSAALSSTISNVVSQIGASNPGLSGCDVLIQALLEVVSALIQILGSSSIGQVNYGSAGQATQIVGQSVYQALG
配列番号59:
>gi|13562006|gb|AAK30606.1|AF350277_1 大瓶状腺スピドロイン1(マダガスカルジョロウグモ)
GLGGQGAGQGAGAAAAAAGGAGQGGYGGLGSQGAGRGGYGGQGAGAAAAAAAGGAGQGGYGGLGSQGAGQGGYGGLGGQGAGQGAAAAAAAGGAGQGGYGGLGSQGAGRGGYGGQGAGAAAAATGGAGQGGYGGVGSGASAASAAASRLSSPQASSRVSSAVSNLVASGPTNSAALSSTISNAVSQIGASNPGLSGCDVLIQALLEVVSALIHILGSSSIGQVNYGSAGQATQ
配列番号60:
>gi|13562022|gb|AAK30614.1|AF350285_1 大瓶状腺スピドロイン1(テトラグナータ・カウアイエンシス(Tetragnathakauaiensis))
SGLGGAGQGAGQGASAAAAAAAXGGLGGGQGAGQGGQQGAGQGGYGSGLGGAGQGASAAAAAAAAGGLGGGQGAGQGGQQGAGQGGYGSGLGGAGQGASAAAAAAAAGGLGGGQGAGQGGQQGAGQGGYGSGLGGAGQGAGQGASAAAAAAAGGLGGGQGGYGSGLGGVGQGGQGALGGSRNSATNAISNSASNAVSLLSSPASNARISSAVSALASGAASGPGYLSSVISNVVSQVSSNSGGLVGCDTLVQALLEAAAALVHVLASSSGGQVNLNTAGYTSQL
配列番号61:
>gi|13562010|gb|AAK30608.1|AF350279_1 大瓶状腺スピドロイン1(アフリカジョロウグモ)
GLGGQGAGRGAGAAAAAAGGAGQGGYGGLGGQGAGAAAAAAGGAGQGGQGLGGRGAAAAGGAGQGGYGGLGGQGAGRGAGAAAAAAGGAGQGGYGGLGGQGAGAAAAAAAAGGAGQGGYGGLGSQGAGRGGYGGQGAGAAVAAIGGVGQGGYGGVGSGASAASAAASRLSSPEASSRVSSAVSNLVSSGPTNSAALSSTISNVVSQIGASNPGLSGCDVLIQALLEVVSALVHILGSSSIGQVNYGSAGQATQ
配列番号62:
>gi|13562024|gb|AAK30615.1|AF350286_1 大瓶状腺スピドロイン1(テトラグナータ・ベルシカラー(Tetragnatha versicolor))
SGQGASAAAAAAGGLGGGQGGYGSGLGGAGQGGQQGAGQGAAAAAASAAAGGLGGGQGGQQGAGRGGLQGAGQGGQGALGGSRNSAANAVSRLSSPASNARISSAVSALASGGASSPGYLSSIISNVVSQVSSNNDGLSGCDTVVQALLEVAAALVHVLASSNIGQVNLNTAGYTSQL
配列番号63:
>gi|13561998|gb|AAK30602.1|AF350273_1 大瓶状腺スピドロイン1(ラトロデクツス・ゲオメトリクス)
AGSGQGGYGQGYGEGGAGQGGAGAAAAAAAAAGGAGQGGQGGYGQGYGQGGAGQGGAGAAAAAAAGGAGQGGYGRGGAGQGAAAAAAAAGSGQGGQGGYGQGYGQGGAGQGGAGAAAAAAAAGGAGQGGYGRGGAGQGGAAAAAAAAGGAGQGGQGGYGQGYGQGGAGQGGAGAAAAAAAAGGAGQGGYGRGGAGQGGSAAAAAAAGGAGQGGYGRGGAGQGGAGSAAAAAAAGGSGQGGQGGYGQGYGQGGAGQGGAAAAASALAAPATSARISSHASTLLSNGPTNPASISNVISNAVSQISSSNPGASSCDVLVQALLELVTALLTIIGSSNVGNVNYDSSGQYAQVVSQSVQNAFV
配列番号64:
>gi|13561984|gb|AAK30595.1|AF350266_1 大瓶状腺スピドロイン1(アルギオープ・トリファシアタ)
AAAAAAAAAGGQGGQGGYDGLGSQGAGQGGYGQGGAAAAAAAASGAGSAQRGGLGAGGAGQGYGAGSGGQGGAGQGGAAAATAAAAGGQGGQGGYGGLGSQGSGQGGYGQGGAAAAAAAASGDGGAGQEGLGAGGAGQGYGAGLGGQGGAGQGGAAAAAAAAAGGQGGQGGYGGLGSQGAGQGGYGQGGAAAAAAAASGAGGAGQGGLGAAGAGQGYGAGSGGQGGAGQGGAAAAAAAAAGGQGGQGGYGGLGSQGAGQGGYGQGGVAAAAAAASGAGGAGRGGLGAGGAGQEYGAVSGGQGGAGQGGEAAAAAAAAGGQGGQGGYGGLGSQGAGQGGYGQGGAAAAAAAASGAGGARRGGLGAGGAGQGYGAGLGGQGGAGQGSASAAAAAAAGGQGGQGGYGGLGSQGSGQGGYGQGGAAAAAAAASGAGGAGRGSLGAGGAGQGYGAGLGGQGGAGQGGAAAAASAAAGGQGGQGGYGGLGSQGAGQGGYGQGGAAAAAASAGGQGGQGGYGGLGSQGAGQGGYGGGAFSGQQGGAASVATASAAASRLSSPGAASRVSSAVTSLVSSGGPTNSAALSNTISNVVSQISSSNPGLSGCDVLVQALLEIVSALVHILGSANIGQVNSSGVGRSASIVGQSINQAFS
大瓶状腺スピドロイン2
配列番号65:
>gi|50363155|gb|AAT75317.1|大瓶状腺スピドロイン2(アメリカジョロウグモ)
GGYGPGQQGPGGYGPGQQGPSGSGSAAAAAAAGPGQQGPGGYGPGQQGPGGYGPGQQGPSGPGSAAAAAAAAAGPGGYGPAQQGPSGPGIAASAASAGPGGYGPAQQGPAGYGPGSAVAASAGAGSAGYGPGSQASAAASRLASPDSGARVASAVSNLVSSGPTSSAALSSVISNAVSQIGASNPGLSGCDVLIQALLEIVSACVTILSSSSIGQVNYGAASQFAQVVGQSVLSAF
配列番号66:
>gi|50363153|gb|AAT75316.1|大瓶状腺スピドロイン2(アメリカジョロウグモ)
PGGYGPGQQGPSGAGSAAAAAAAGPGQQGLGGYGPGQQGPGGYGPGQQGPGGYGPGSASAAAAAAGPGQQGPGGYGPGQQGPSGPGSASAAAAAAAAGPGGYGPGQQGPGGYAPGQQGPSGPGSAAAAAAAAAGPGGYGPAQQGPSGPGIAASAASAGPGGYGPAQQGPAGYGPGSAVAASAGAGSAGYGPGSQASAAASRLASPDSGARVASAVSNLVSSGPTSSAALSSVISNAVSQIGASNPGLSGCDVLIQALLEIVSACVTILSSSSIGQVNYGAASQFAQVVGQSVLSAF
配列番号67:
>gi|50363147|gb|AAT75313.1|大瓶状腺スピドロイン2(アメリカジョロウグモ)
GPGGYRPGQQGPSGPGSAAAAAAAAAGPGGYGPGQQGPGGYGPGQQGPSGAGSAAAAAAAGPGQQGLGGYGPGQQGPGGYGPGQQGPGGYGPGSASAAAAAAGPGQQGPGGYGPGQQGPSGPGSASAAAAAAGPGGYGPGQQGPGGYAPGQQGPSGPGSAAAAAAAARAGPGGYGPAQQGPSGPGIAASAASAGPGGYGPAQQGPAGYGPGSAVAASAGAGSAGYGPGSQASAAASRLASPDSGARVASAVSNLVSSGPTSSAALSSVISNAVSQIGASNPGLSGCDVLIQALLEIVSACVTILSSSSIGQVNYGAASQFAQVVGQSVLSAF
配列番号68:
>gi|50363151|gb|AAT75315.1|大瓶状腺スピドロイン2(アメリカジョロウグモ)
GRGAGQQGPGGYGPGQQGPGGYGPGQQGPSGPGSAAAAAAAASGPGQQGPGGYGPGQQGPGGYGPGQQSPSGPGSAAAAAAAAAGPGQQGPGGYGPGQQGPSGPGSASAAAAAAGPGGYGPGQQGPGGYAPGQQGPSGPGSAAAAAAARAGPGGYGPAQQGPSGPGIAASAASAGPGGYGPAQQGPAGYGPGSAVAASAGAGSAGYGPGSQASAAASRLASPDSGARVASAVSNLVSSGPTSSAALSSVISNAVSQIGASNPGLSGCDVLIQALLEIVSACVTILSSSSIGQVNYGAASQFAQVVGQSVLSAF
配列番号69:
>gi|50363149|gb|AAT75314.1|大瓶状腺スピドロイン2(アメリカジョロウグモ)
SAAAAAAAAAGPGGYGPGQQGPGGYGPGQQGPSGAGSAAAAAGPGQQGLGGYGPGQQGPGGYGPGQQGPGGYGPGSASAAAAAAGPGQQGPGGYGPGQQGPSGPGSASAAAAAAGPGGYGPGQQGPGGYAPGQQGPSGPGSAAAAAAAAAGPGGYGPAQQGPSGPGIAASAASAGPGGYGPAQQGPAGYGPGSAVAASAGAGSAGYGPGSQASAAASRLASPDSGARVASAVSNLVSSGPTSSAALSSVISNAVSQIGASNPGLSGCDVLIQALLEIVSACVTILSSSSIGQVNYGAASQFAQVVGQSVLSAF
配列番号70:
>gi|13562012|gb|AAK30609.1|AF350280_1 大瓶状腺スピドロイン2(アフリカジョロウグモ)
QGPGGYGPSGPGSAAAASAAAGPGQQGPGAYGPSGPGSAAAAAGPGXYGPGQQGPSGPGAAAAAAGPGQQGPGGYGPGAAAAAAAAAGPGQQGPVAYGPSGPGSAASAAGPGGYGPARYGPSGSAAAAAAAGAGSAGYGPGPQASAAASRLASPDSGARVASAVSNLVSSGPTSSAALSSVIXNAVSQIGASNPGLSGCDVLIXALLEIVSACVTILSSSSIGQVNYGAA
配列番号71:
>gi|13562008|gb|AAK30607.1|AF350278_1 大瓶状腺スピドロイン2(マダガスカルジョロウグモ)
QGPSGPGSAAAAAAAGPGQQGPGGYGPGQQGPGGYGPGQQGPSGPGSAAAAAAAAAAGPGQQGPGGYGPGPQGPGGYGPGQQGPSGYGPGQQGPSGPGSAASAAAAAGSGQQGPGGYGPGQQGPGGYGPGQQGPSGPGSAAAAAAAGPGQQGPGGYGPGQQGPGGYGPGQQGPSGPGSAAAAAAAAGPGQQGPGGYGPGQQGPGGYGPGQQGPSGPGSAAAAAAAGPGQQGPGGYGPGQQGPGGYGPGQQGPSGPGSAAAAAAAAAGPGQQGPGGYGPGQQGPGQQGPSGPGSAAAAAAAGPGPQGPGGYGPGQQGPGGYGPSGPGSAAAAAAAAGPGQQGPGGYGPGQQRPSGYGPGQQGPSGPGSAAAAAAAGPGQQGPGAYGPSGPGSAAAAAGLGGYGPAQQGPSGAGSAAAAAAAGPGGYGPVQQGPSGPGSAAGPGGYGPAQQGPARYGPGSAAAAAAAAGSAGYGPGPQASAAASRLASPDSGARVASAVSNLVSSGPTSSAALSSVISNAVSQIGASNPGLSGCDVLIQALLEIVSACVTILSSSSIGQVNYGAA
配列番号72:
>gi|13562002|gb|AAK30604.1|AF350275_1 大瓶状腺スピドロイン2(ラトロデクツス・ゲオメトリクス)
AGPGSYGPSGPGGSGAAAAAAAASGPGGQQGYGPGGPGASAAAAAAAGGSGPGGYGQGPSGYGPSGPGAQQGYGPGGQGGSGAAAAAAAAAGSGPGGYGPGAAGPGNYGPSGPGGSGAAASAAAASGPGGQQGYGPGGSGAAAAAASGGAGPGRQQGYGPGGSGAAAAAAAAXGGSGPGGYGQGPXGYGPGGQGGSGGAAAAAAAASSGPXGYGPGAAGPGNYGPSGPGGSGAAAAAAAASGPGGQQGYGPGGSGASAAAAAGGAGXGRQQAYGPGGSGAAAAAASGSGGYGPAQYGXSSVASSAASAASALSSPTTHARISSHASTLLSSGPTNSAAISNVISNAVSQVSASNPGSSSCDVLVQALLELITALISIVDSSNIGQVNYGSSGQYAQMVG
配列番号73:
>gi|13561986|gb|AAK30596.1|AF350267_1 大瓶状腺スピドロイン2(アルギオープ・トリファシアタ)
AGPGYGPGAGQQGPGSQGPGSGGQQGPGGQGPYGPSAAAAAAAAGPGYGPGAGQQGPGSGGQQGGQGSGQQGPGGAGQGGPRGQGPYGPGAAAAAAAAGGYGPGAGQQGPGSQGPGSGGQQGPGSQGPYGPSAAAAAAAAGPGYGPGAGQQGPGSQGPGSGGQQGPGGQGPYGPSDAAAAAAAGPGYGPGAGQQGPGSGGQQGGQGSGQQGPGGAGQGGPRGQGPYGPGAAAAAAAAGGYGPGAGQQGPGSQGPGSGGQQGPGSQGPYGPSAAAAAAAAGPGYGPGAGQQGPGSQGPGSGGQQGPGSQGPYGPSAAAAAAAAGPGYGPGAGQQGPGSQAPVASAAASRLSSPQASSRVSSAVSTLVSSGPTNPASLSNAISSVVSQVSSSNPGLSGCDVLVQALLEIVSALVHILGSSSIGQINYAASSQYAQLVGQSLTQALG
配列番号74:
>gi|13561978|gb|AAK30592.1|AF350263_1 大瓶状腺スピドロイン2(アルギオープ・アウランチア)
PGGAGQQGPGGQGPYGPGAAAAAAAAGGYGPGAGQQGPXGAGQQGPGSQGPGGAGQQGPGGQGPYGPGAAAAAAAVGGYGPGAGQQGPGSQGPGSGGQQGPGGQGPYGPSAAAAAAAAGGYGPGAGQQGPGSQGPGSGGQQGPGGLGPYGPSAAAAAAAAGGYGPGAGQQGPGSQGPGSGGQQRPGGLGPYGPSAAAAAAAAGGYGPGAGQQGPGSQGPGSGGQQRPGGLGPYGPSAAAAAAAAGGYGPGAGQQGPGSQAPVASAAASRLSSPQASSRVSSAVSTLVSSGPTNPAALSNAISSVVSQVSASNPGLSGCDVLVQALLELVSALVHILGSSSIGQINYAAS
配列番号75:
>gi|70913274|gb|AAZ15372.1|大瓶状腺スピドロイン2(アルギオープ・トリファシアタ)
GQGSGQQRPGGAGQGGLGPYGPGAAAAAAAAAGGYGPGAGQQGPGSQGPGSGGQQGPGSRGPYGPSAAAAAAAAGPGYGPGAGQRGPRSQGPGSGGQQGPGGQGPYGPSAAAAAAAAGPGYGPGAGQQGPGSQAPVASAAASRLSSPQASSRVSSAVSTLVSSGPTNPASLSNAISSVVSQVSASNPGLSGCDVLVQALLEIVSALVHILGSSSIGQINYAASSQYAQMVG
配列番号76:
>gi|70913273|gb|AAZ15371.1|大瓶状腺スピドロイン2(アルギオープ・トリファシアタ)
MNWSIRLALLGFVVLSTQTVFSAGQGATPWENSQLAESFISRFLRFIGQSGAFSPNQLDDMSSIGDTLKTAIEKMAQSRKSSKSKLQALNMAFASSMAEIAVAEQGGLSLEAKTNAIASALSAAFLETTGYVNQQFVNEIKTLIFMIAQASSNEISGSAAAAGGSSGGGGGSGQGGYGQGAYASASAAAAYGSAPQGTGGPASQGPSQQGPVSQPSYGPSATVAVTAVGGRPQGPSAPRQQGPSQQGPGQQGPGGRGPYGPSAAAAAAAAGGYGPGAGQQGQQAGQGSGQQGPGGAGQGGPRGQGPYGPGAATAAAAAAGPGYGPGAGQQGPGSQGPGSGGQQGPGSQGPYGPSAAAAAAAAGPGYGPGAGQQGPGSQGPRSGGQQGPGGQGPYGPSAAAAAAAAGPGYGPGAGQQGPGSGGQQGGPGSGQQGPGGAGQGGPRGQGPYGPGAAAAAAAAAGGYGPGAGQQGPGSQGPGSGGQQGPGSQGPYGPSAAAAAAAAGPGYGPGAGQQGPGSQGPGSGGQQGPGGQGPYGPSAAAAAAAAGPGYGPGAGQQGPGSGGQQGGQGSGQQGPGGAGQGGPRGQGPYGPGAAAAAAAAAGGYGPGAGQQGPGSQGPGSGGQQGPGSQGPYGPSAAAAAAAAGPGYGPGAGQQGPGSGGQQ
配列番号77:
>gi|164709224|gb|ABY67417.1|大瓶状腺スピドロイン2(ラトロデクツス・ゲオメトリクス)
LRWSSKDNADRFINAFLQAASNSGAFSSDQVDDMSVIGNTLMTAMDNMGGRITPSKLQALDMAFASSVAEIAVADGQNVGGATNAISNALRSAFYQTTGVVNNQFISEISNLINMFAQVSANEVSYASGGSSSAAASAAASAGPAAQQVYAPSAGAPAAATASSGPGAYGPSAPGGPSAAAAAAASGGAGPGRQQSYGPGGSGAAAAAAATGGSGPGGYGQGPASYAPSGPGGQQGYGPGGSGAASAAAAAASSGPGGYGPGASGPGSYGPSGPGGSGAAAAAAAASAPGGQQGYGPGGSGAAAAAAAGGAGPGSQQAYGPGGSGAAAAAAAGPGSGGQQGYGPGGSAAAAAAAAAGGSGPGGYGQGPAGYGPSGPGAQQGYGPGGPG
配列番号78:
>gi|13561996|gb|AAK30601.1|AF350272_1 大瓶状腺スピドロイン2(ガステラカンタ・マモサ)
GQQGPGSQGPYGPGAAAAAAAAAGGYRPVSGQQGPGQQGPGSGGQQGPGGQRPYGPGAAAAAAAAGGYGPGSGQGGPGQQGPGSGGQQGPGGQGPYGPGAAAAAAAAAGGYGPGSGQGGQQGPGSQGPGSGGQQGPGGQGPYGPSAAAAAAAVGGYGPGAGQQGPGQQGPGSGGQRGPGGQGPYGPGAAAAAAAAAGGYGPASGQQGPGQQGPGSGGQRGPGGQGPYGPGAAAAASAGGYGPGSGGSPASGAASRLSSPQAGARVSSAVSALVASGPTSPAAVSSAISNVASQISASNPGLSGCDVLVQALLEIVSALVSILSSASIGQINYGASGQYAAMI
小瓶状腺シルクタンパク質
配列番号79:
>gi|2605800|gb|AAC14590.1|小瓶状腺シルクタンパク質(アメリカジョロウグモ)
GAGGYGRGAGAGAAAVAGADAGGYGRNYGAGTTAYAGARAGGAGGYGGQGGYSSGAGAAAASGAGADITSGYGRGVGAGAGAETIGAGGYGGGAGSGARAASASGAGTGYGSSGGYNVGTGISTSSGAASSYSVSAGGYASTGVGIGSTVTSTTSRLSSAEACSRISAAASTLVSGSLNTAALPSVISDLFAQVSASSPGVSGNEVLIQVLLEIVSSLIHILSSSSVGQVDFSSVGSSAAAVGQSMQVVMG
配列番号80:
>gi|2605802|gb|AAC14591.1|小瓶状腺シルクタンパク質MiSp2(アメリカジョロウグモ)
SYGPSVFYTPTSAGSYGAGAGGFGAGASAGVGAGAGTVAGYGGQGGYGAGSAGGYGRGTGAGAAAGAGAGATAGAGAGAAAGAGAGAGNSGGYSAGVGVGAAAAAAGGGAGTVGGYGRGAGVGAGAAAGFAAGAGGAGGYRRDGGYGAGAGAGAAAA
配列番号81:
>gi|2605798|gb|AAC14589.1|小瓶状腺シルクタンパク質MiSp1(アメリカジョロウグモ)
RGAASGAGAAAGAGAGAGGAGYGGQIGYGAGAGAGAAAAAGAGAGGAAGYGRGAGAGSGAAAGAGSGAGAGGYGGQAGYGAGAGAGSSAGNAFAQSLSSNLLSSGDFVQMISSTTSTDHAVSVATSVAQNVGSQLGLDANAMNNLLGAVSGYVSTLGNAISDASAYANALSSAIGNVLANSGSISESTASSAASSAASSVTTTLTSYGPAVFYAPSASSGGYGAGAGAVAAAGAAGAGGYGRGAGGYGGQGGYGAGAGAGAAAAAGAGAGGAGGYGRGAGAGAGAAAGAGAGAGGAGYGGQGGYGAGAGAGAAAAAGAGAGGAGGYGRGAGAGAGAAAGAGAGGYGGQGGYGAGAGAGAAAAAAGAGSGGAGGYGRGAGAGAGAAAGAGAGAGSYGGQGGYGAGAGAGAAAAAGAGAGAGGYGRGAGAGAGAGAGAAARAGAGAGGAGYGGQGGYGAGAGAGAAAAAGAGAGGAGGYGRGAGAGAGAAAGAGAGAGGYGGQSGYGAGAGAAAAAGAGAGGAGGYGRGAGAGAGAAAGAGAGAAAGAGAGGYGGQGGYGAGAGAGAAAAAGAGAGGAGGYGRGAGAGAGVAAGAGAGGYGGQGGYGAGAGAGAAAAAATGAGGAGGYGRGAGAGAGAAAGAGAGTGGAGYGGQGGYGAGAGAGAAAAAGAGAGGAGYGRGAGAGAGAAAGAGAGAAAGAGAGAGGYGGQGGYGAGAGAGAAAAAGAGAGGAAGYSRGGRAGAAGAGAGAAAGAGAGAGGYGGQGGYGAGAGAGAAAAAGAGSGGAGGYGRGAGAGAAAGAGAAAGAGAGAGGYGGQGGYGAGAGAAAAAGAGAGRGGYGRGAGAGGYGGQGGYGAGAGAGAAAAAGAGAGGYGDKEIACWSRCRYTVASTTSRLSSAEASSRISSAASTLVSGGYLNTAALPSVISDLFAQVGASSPGVSDSEVLIQVLLEIVSSLIHILSSSSVGQVDFSSVGSSAAAVGQSMQVVMG
鞭毛状シルクタンパク質
配列番号82:
>gi|2833649|gb|AAC38847.1|鞭毛状シルクタンパク質(アメリカジョロウグモ)
GPGGVGPGGSGPGGYGPGGAGPGGYGPGGSGPGGYGPGGSGPGGYGPGGSGPGGYGPGGSGPGGYGPGGSGPGGYGPGGYGPGGSGPGGYGPGGTGPGGSGPGGYGPGGSGPGGSGPGGYGPGGSGPGGFGPGGSGPGGYGPGGSGPGGAGPGGVGPGGFGPGGAGPGGAGPGGAGPGGAGPGGAGPGGAGPGGAGPGGAGPGGAGPGGAGPGGAGGAGGAGGAGGSGGAGGSGGTTIIEDLDITIDGADGPITISEELTISGAGGSGPGGAGPGGVGPGGSGPGGVGPGGSGPGGVGPGGSGPGGVGPGGAGGPYGPGGSGPGGAGGAGGPGGAYGPGGSYGPGGSGGPGGAGGPYGPGGEGPGGAGGPYGPGGAGGPYGPGGAGGPYGPGGEGGPYGPGGSYGPGGAGGPYGPGGPYGPGGEGPGGAGGPYGPGGVGPGGSGPGGYGPGGSGPGGYGPGGAGPGGYGPGGSGPGGYGPGGSGPGGYGPGGSGPGGYGPGGSGPGGYGSGGAGPGGYGPGGSGPGGYGPGGSGPGGYGPGGTGPGGTGPGGSGPGGYGPGGSGPGGSGPGGSGPGGYGPSGSGPGGYGPSGSGPGGYGPGGSGPGGYGPGGSGAGGTGPGGAGGAGGAGGSGGAGGSGGAGGSGGAGGSGGVGGSGGTTITEDLDITIDGADGPITISEELTISGAGGSGPGGAGPGGVGPGGSGPGGVGPGVSGPGGVGPGGSGPGGVGSGGSGPGGVGPGGYGPGGSGSGGVGPGGYGPGGSGGFYGPGGSEGPYGPSGTYGSGGGYGPGGAGGPYGPGSPGGAYGPGSPGGAYYPSSRVPDMVNGIMSAMQGSGFNYQMFGNMLSQYSSGSGTCNPNNVNVLMDALLAALHCLSNHGSSSFAPSPTPAAMSAYSNSVGRMFAY
配列番号83:
>gi|2833647|gb|AAC38846.1|鞭毛状シルクタンパク質(アメリカジョロウグモ)
MGKGRHDTKAKAKAMQVALASSIAELVIAESSGGDVQRKTNVISNALRNALMSTTGSPNEEFVHEVQDLIQMLSQEQINEVDTSGPGQYYRSSSSGGGGGGQGGPVVTETLTVTVGGSGGGQPSGAGPSGTGGYAPTGYAPSGSGAGGVRPSASGPSGSGPSGGSRPSSSGPSGTRPSPNGASGSSPGGIAPGGSNSGGAGVSGATGGPASSGSYGPGSTGGTYGPSGGSEPFGPGVAGGPYSPGGAGPGGAGGAYGPGGVGTGGAGPGGYGPGGAGPGGYGPGGAGPGGYGPGGAGPGGYGPGGAGPGGYGPGGAGPGGYGPGGAGPGGYGPGGTGPGGYGPGGTGPGGVGPGGAGPGGYGPGGAGPGGAGPGGAGPGGAGPGGAGPGGAGPGGYGPGGSGPGGAGPSGAGLGGAGPGGAGLGGAGPGGAGTSGAGPGGAGPGGAGQGDAGPGGAGRGGAGRGGVGRGGAGRGGAGRGGARGAGGAGGAGGAGGSGGTTIVEDLDITIDGADGPITISEELTIGGAGAGGSGPGGAGPGNVGPGRSGPGGVGPGGSGPGGVGPGSFGPGGVGPGGSGPGGVGSGGSGQGGVRPSGSGPGGVGTGGVGPGGAGGPYGPGGSGPGSAGSAGGTYGPGGFGGPGGFGGPGGAGGPYGPGGAGGPYGPGGAGGPYGPGGAGGPYGPGGAGGPYGPGGAGGSYGLGGAGGSGGVGPGGSGPGGYGPGGAGPGGYGPGGSGPGGYGPGGSGSGGYGPGGSGPGGSGPGGYGPGGTGPGGSESGGYGPGGSGPGGSGPGGSGPGGSGPGGYGPGGSGPSSFVPGGSGPGGSGPGGAGPGGAGPGGVGLGGAGRGGAGRGGAGSVGAGRGGAGRGGTG
配列番号84:
>gi|13561982|gb|AAK30594.1|AF350265_1 鞭毛状シルクタンパク質(アルギオープ・トリファシアタ)
GAPGGGPGGAGPGGAGFGPGGGAGFGPGGGAGFGPGGAAGGPGGPGGPGGPGGAGGYGPGGAGGYGPGGVGPGGAGGYGPGGAGGYGPGGSGPGGAGPGGAGGEGPVTVDVDVTVGPEGVGGGPGGAGPGGAGFGPGGGAGFGPGGAPGAPGGPGGPGGPGGPGGPGGVGPGGAGGYGPGGAGGVGPAGTGGFGPGGAGGFGPGGAGGFGPGGAGGFGPGGAGGYGPGGVGPGGAGGFGPGGVGPGGSGPGGAGGEGPVTVDVDVSVGGAPGGGPGGAGPGGAGFGPGGGAGFGPGGGAGFGPGGAAGGPGGPGGPGGPGGAGGYGPGGAGGYGPGGVGPGGAGGYGPGGAGGYGPGGSGPGGAGPGGAGGEGPVTVDVDVTVGPEGVGGGPGGAGPGGAGFGPGGGAGFGPGGAPGAPGGPGGPGGPGGPGGPGGVGPGGAGGYGPGGAGGVGPAGTGGFGPGGAGGFGPGGAGGFGPGGAGGFGPAGAGGYGPGGVGPGGAGGFGPGGVGPGGSGPGGAGGEGPVTVDVDVSVGGAPGGGPGGAGPGGAGFGPGGGAGFGPGGGAGFGPGGAAGGPGGPGGPGGPGGAGGYGPGGAGGYGPGGVGPGGAGGYGPGGAGGYGPGGSGPGGAGPGGAGGEGPVTVDVDVTVGPEGVGGGPGGAGPGGAGFGPGGGAGFGPGGAPGAPGGPGGPGGPGGPGGPGGVGPGGAGGYGPGGAGGFGPGGTGGFGPGGAGGFGPGGAGGFGPGGAGGFGPGGAGGYGPGGVGPGGAGGFGPGGVGPGGSGPGGAGGEGPVTVDVDVSVGGAPGGGPGGAGPGGAGFGPGGGAGFGPGGGAGFGPGGAAGGPSGPGGPGGPGGAGGYGPGGAGGYGPGGVGPGGAGGYGPGGAGGYGPGGSGPGGAGPGGAGGEGPVTVDVDVTVGPEGVGGGPGGAGPGGAGFGPGGGAGFGPGGAPGAPGGPGGPGGPGGPGGPGGVGPGGAGGYGPGGAGGVGPAGTGGFGPGGA
配列番号85:
>gi|7106229|gb|AAF36092.1|鞭毛状シルクタンパク質(マダガスカルジョロウグモ)
SGGSGGTTVIEDLDITIDGADGPITISEELTISGAGAGGSGPGGAGPGGVGPGGSGPGGVGPGGSGPGGVGPGGAGGPYGPGGSGPGGAGGAGGPGGAYGPGGSGGPGGAGGPYGPGGEGPGGAGGPYGPGGEGPGGAGGPYGPGGAGGPYGPGGAGGPYGPGGAGGPYGPGGAGGPYGPGGVGPGGTGPGGYGPGGAGPGGYGPGGSGPGGYGPGGSGPGGYGPGGSGPGGFGPGGSGPGGSGPGGSGPGGYGPGGSGPGGYGPGGSGPGGYGPGGSGPGGYGPGGSGPGGSGPGGYGPGGSGPGGYGPGGSGPGGAGPGGAGPGGVGPGGAGPGGAGPGGVGPGGAGPGGAGPGGAGPGGAGRGGAGPGGAGGAGGAGGSGGAGGSGGTTVIEDLDITIDGADGPITISEELTIGGAGGSGPGGAGGSGPGGAGPGGVGPGGSGPGGLGSGGSGPGGVGPGGSGPGGVGPGGYGPGGSGGLYGPGSYGPGGSGVPYGSSGTYGSGGGYGPGGAGGAYGPGSPGGAYGPGSGGSYYPSSRVPDMVNGIMSAMQGSGFNYQMFGNMLSQYSSGSGSCNPNNVNVLMDALLAALHCLSNHGSSSFAPSPTPAAMSAYSNSVGRMFAY
配列番号86:
>gi|13561980|gb|AAK30593.1|AF350264_1 鞭毛状シルクタンパク質(アルギオープ・トリファシアタ)
AGGPGAGGAGAGGVGPGGFGGPGGFGGAGGPGGPGGPGGAGGGAGGAGGLYGPGGAGGLYGPGGLYGPGGAGVPGAPGASGRAGGIGGAAGGAGAGGVGPGGVSGGAGGAGGSGVTVVESVSVGGAGGPGAGGVGPGGVGPGGVGPGGIYGPGGAGGLYGPGAGGAFGPGGGAGAPGGPGGPGGPGGPGGLGGGVGGAGTGGGVGPGAGGVGPSGGAGGTGPVSVSSTVSVGGAGGPGAGGPGAGGAGAGGVGPGGFGGPGGFGGAGGPGGPGGPGGAGGGAGGAGGLYGPGGAGGLYGPGGLYGPGGAGVPGAPGASGRAGGIGGAAGAGGVGPGGVSGGAGGSGVSVTESVTVGGAGGAGAGGIGGPSGLGGAGATGGFGGRGGPGGPGGPGGPGRFGGAAGGAGAGGVGPGGVSGGAGGAGGSGVTVVESVSVGGAGGPGAGGVGPGGVGPGGVGPGGIYGPGGAGGLYGPGAGGAFGSGGGAGAPGGPGGPGGPGGPGGLGGGVGGAGTGGGVGPGVGGVGPSGGAGGTGPVSVSSTITVGGGQSSGGVLPSTSYAPTTSGYERLPNLINGIKSSMQGGGFNYQNFGNILSQYATGSGTCNYYDINLLMDALLAALHTLNYQGASYVPSYPSPSEMLSYTENVRRYF
配列番号87:
>gi|7106228|gb|AAF36091.1|鞭毛状シルクタンパク質(マダガスカルジョロウグモ)
MGKGRHDTKAKAKAMQVALASSIAELVIAESSGGDVQRKTNVISNALRNALMSTTGSPNEEFVHEVQDLIQMLSQEQINEVDTSGPGQYYRSSSSGGGGGGGGGPVITETLTVTVGGSGAGQPSGAGPSGTGGYAPTGYAPSGSGPGGVRPSASGPSGSGPSGSRPSSSGSSGTRPSANAAGGSSPGGIAPGGSSPGGAGVSGATGGPASSGSYGSGTTGGAYGPGGGSEPFGPGAAGGQYGPGGAGPGGAGAYGPGGVGPGGAGPGGYGPGGAGPGGYGPGGAGPGGYGPGGAGPGGYGPGGAGPGGYGPGGAGPGGYGPGGAGPGGYGPGGSGTGGAGPGGYTPGGAGPGGYGPGGYGPGGSGPGGAGSGGVGPGGYGPGGAGPGGAGPGGAGPGGAGPSGAGPGGAGTGGAGTGGAGPGGAGPGGAGPGGAGPGGAGRGGAGRGGAGRGGAGRGGAGRGGAGRGGAGGAGGAGGAGGAGGAGGAGGSGSTTIIEDLDITIDGADGPITISEELTIGGAGAGGSGPGGAGPGGVGPGRSGPGGVGPGGSGPGSVGPGGSGQGGLGIGRSGPGGVGPGGSGPGSIGPGGSGQGGLGPGGSGQGGLGPGGSGPGGVGSGGVGGPYGPGGSGPGGVGGAGGPYGPGGSGGPGGAGGPYGPGGPYGPGGAGGPYGPGGAGGPYGPGGPYGPGGAGGPGGGGPGGAGGPYGPGGPGGAGPGGYGPGGYGPGGAGPGGAGPGGYGPGGAGPGGYGPGGAGPGGSGPGGIGPGGSGPGGYGPGGIGPGGTGPGGAGPGGAGPGGAGPSGAGPGGAGPSGAGRGGSGRGSVGRGGAGRGGAGRGGAGGAGGSGGAGGSGGAGGSGGTTIIEDLDITVDGANGPITISEELTIGGAGAGGVGPGGSGPGGVGPGGSGPGGVGPGGSGPGGVGSGGSGPGGVGPGGSGPGGVGSGGFGPGGIGPGGSGPGGVGPGGVGGPYGPGGSGPGGAGGAGGSYGPGGPYGPGGSGGPGGAGGPYGPGGAGGPYGPGGPYGPGGAGGPGGEGPGGAGGPYGPGGPGGAGPGGYGPGGAGPGGYGPGGAGPGGYGPGGAGSGGYGPGGAGPGGYGPGGPGPGGYGPGGAGPGGYGPGGTGPGGSAPGGAGPGGAGPGGYGPGGSGPGGYGPGGGPGGAGPGGAGPGGAGPGGAGPGGAGPGGAGPGGAGPGGAGPGGAGPGGAGPGGVGTGGLGRGGAGRGGAGRGGAGRGGAGRGGAGRGGTGGVGGAGGAGGAGGVGGAGGSGGTTVIEDLDITIDGADGPITISEELTISGAGAGGSGPGGAGPGGVGPGGSGPGGVGPGGSGPGGVGPGGAGGPYRPGGSGPGGAGGAGGPGGAYGPGGSGGPGGAGGPYGPGGEGPGGSGGPYGPGGEGPGGAGGPYGPGGAGGPYGPGGAGGPYGPGGAGGPYGPGGAGGPYGPGGAGGPYGPGGAGGPYGPGGEGPGGAGGPYGPGGVGPGGTGPGGYGPGGAGPGGYGPGGSGPGGYGPGGSGPGGFGPGGSGPGGYGPGGSGPGGYGPGGSGPGGAGPGGYGPGGTGPGGSGPGGYGPGGSGPGGYGPGGSGPGGYGPGGSGPGGAGPGGAGPGGAGPGGAGPGGVGPGGAGPGGSGPGGAGPGGAGRGGAGRGGAGXGGAGPGGAGGAGGAGGSGGAGGSGGTTVIEDLDITIDGADGPITISEELTINGAGAGGSGPGGAGPGGVGPGGSGPGGVGPGGSGPGGVGPGGAGGPYGPGGSGPGGAGGAGGPGGAYGPGGSGGPGGAGGPYGPGGEGPGGAGGPYGPGGEGPGGAGGPYGPGGAGGPYGPGGAGGPYGPGGAGGPYGPGGAGGPYGPGGAGGPYGPGGAGGPYGPGGEGPGGAGGPYGPG
配列番号88:
>gi|7106224|gb|AAF36090.1|鞭毛状シルクタンパク質(アメリカジョロウグモ)
AGPSGTGGYAPTGYAPSGSGAGGVRPSASGPSGSGPSGGSRPSSSGPSGTRPSPNGASGSSPGGIAPGGSNSGGAGVSGATGGPASSGSYGPGSTGGTYGPSGGSEPFGPGVAGGPYSPGGAGPGGAGGAYGPGGVGTGGAGPGGYGPGGAGPGGYGPGGAGPGGYGPGGAGPGGYGPGGAGPGGYGPGGAGPGGYGPGGAGPGGYGPGGTGPGGYGPGGTGPGGVGPGGAGPGGYGPGGAGPGGAGPGGAGPGGAGPGGAGPGGYGPGGSGPGGAGPSGAGLGGAGPGGAGLGGAGPGGAGTSGAGPGGAGPGGAGQGGAGPGGAGRGGAGRGGVGRGGAGRGGAGRGGARGAGGAGGAGGAGGSGGTTIVEDLDITIDGADGPITISEELTIGGAGAGGSGPGGAGPGNVGPGRSGPGGVGPGGSGPGGVGPGSFGPGGVGSGGSGPGGVRPSGSGPGGVGTGGVGPGGAGGPYGPGGSGPGGAGSAGGTYGPGGFGGPGGFGGPGGAGGPYGPGGAGGPYGPGGAGGPYGPGGAGGPYGPGGAGGPYGPGGAGGSYGLGGAGGSGGVGPGGSGPGGYGPGGAGPGGYGPGGSGPGGYGPGGSGSGGYGPGGSGPGGSGPGGYGPGGTGPGGSESGGYGPGGSGPGGSGPGGSGPGGSGPGGYGPGGSGPSSFVPGGSGPGGSGPGGAGPGGAGPGGAGPGGAGPGGVGLGGAGRGGAGRGGAGSVGAGRGGAGRGGAGRGGAGRGGAGRGGAGGAGGAGGAGGPGGAGGSGGTTVIEDLDITIDGADGPITISEELTISGAGGSGPGGAGTGGVGPGGSGPGGVGPGGFGPGGVGPGGSGPGGVGPGGAGRPYGPGGSGPGGAGGAGGTGGAYGPGGAYGPGGSGGPGGAGGPGGEGPGGAGGPYGPGGAGGPYGPGGAGGPYGPGGEGGPYGPGVSYGPGGAGGPYGPGGPYGPGGEGPGGAGGPYGPGGVGPGGSGPGGYGPGGAGPGGYGPGGSGPGGYGPGGSGPGGYGPGGSGPGGYGPGGSGPGGYGPGGYGPGGSGPGGSGPGGSGPGGYGPGGTGPGGSGPGGYGPGGSGPGGSGPGGYGPGGSGPGGFGPGGSGPGGYGPGGSGPGGAGPGGVGPGGFGPGGAGPGGAAPGGAGPGGAGPGGAGPGGAGPGGAGPGGAGPGGAGGAGGAGGSGGAGGSGGTTIIEDLDITIDGADGPITISEELPISGAGGSGPGGAGPGGVGPGGSGPGGVGPGGSGPGGVGPGGSGPGGVGPGGAGGPYGPGGSGPGGAGGAGGPGGAYGPGGSYGPGGSGGPGGAGGPYGPGGEGPGGAGGPYGPGGAGGPYGPGGAGGPYGPGGEGGPYGPGGSYGPGGAGGPYGPGGPYGPGGEGPGGAGGPYGPGGVGPGGGGPGGYGPGGAGPGGYGPGGSGPGGYGPGGSGPGGYGPGGSGPGGYGPGGSGPGGYGPGGSGPGGSGPGGYGPGGSGPGGSGPGGYGPGGSGPGGYGPGGSGPGGSGPGGYGPGGSGPGGSGPGGYGPGGSGPGGFGPGGFGPGGSGPGGYGPGGSGPGGAGPGGVGPGGFGPGGAGPGGAGPGGAGPGGAGPGGAGPGGAGPGGAGPGGAGPGGAGGAGGAGGAGGSGGAGGSGGTTIIEDLDITIDGADGPITISEELTISGAGGSGPGGAGPGGVGPGGSGPGGVGPGGSGPGGVGPGGSGPGGVGPGGAGGPYGPGGSGPGGAGGAGGPGGAYGPGGSYGPGGSGGPGGAGGPYGPGGEGPGGAGGPYGPGGAGGPYGPGGAGGPYGPGGEGGPYGPGGSYGPGGAGGPYGPGGPYGPGGEGPGGAGGPYGPGGVGPGGGGPGGYGPGGAGPGGYGPGGSGPGGYGPGGSGPGGYGPGGSGPGGYGPGGSGPGGYGPGGSGPGGSGPGGYGPGGSGPGGYGPGGSGPGGSGPGGYGPGGSGPGGFGPGGFGPGGSGPGGYGPGGSGPGGAGPGGVGPGGFGPGGAGPGGAGPGGAGPGGAGPGGAGPGGAGPGGAGPGGAGPGGAGGAGGAGGAGGSGGAGGSGGTTIIEDLDITIDGADGPITISEELTISGAGGSGPGGAGPGGVGPGGSGPGGVGPGGSGPGGVGPGGSGAGGVGPGGAGGPYGPGGSGPGGAGGAGGPGGAYGPGGSYGPGGSGGPGGAGGPYGPGGEGPGGAGGPYGPGGAGGPYGPGGAGGPYGPGGEGGPYGPGGSYGPGGAGGPYGPGGPYGPGGEGPGGAGGPYGPG
配列番号89:
>gi|7106223|gb|AAF36089.1|鞭毛状シルクタンパク質(アメリカジョロウグモ)
VGPGGSGPGGYGPGGSGPGGYGPGGAGPGGYGPGGSGPGGYGPGGSGPGGYGPGGSGPGGYGPGGSGPGGYGSGGAGPGGYGPGGSGPGGYGPGGSGPGGYGPGGTGPGGTGPGGSGPGGYGPGGSGPGGSGPGGSGPGGYGPSGSGPGGYGPSGSGPGGYGPGGSGPGGYGPGGSGAGGTGPGGAGGAGGAGGSGGAGGSGGAGGSGGAGGSGGVGGSGGTTITEDLDITIDGADGPITISEELTISGAGGSGPGGAGPGGVGPGGSGPGGVGPGVSGPGGVGPGGSGPGGVGSGGSGPGGVGPGGYGPGGSGSGGVGPGGYGPGGSGGFYGPGGSEGPYGPSGPYGSGGGYGPGGAGGPYGPGSPGGAYGPGSPGGAYYPSSRVPDMVNGIMSAMQGSGFNYQMFGNMLSQYSSGSGTCNPNNVNVLMDALLAALHCLSNHGSSSFAPSPTPAAMSAYSN
房状スピドロイン
配列番号90:
>gi|49871101|gb|AAR83925.1|房状スピドロイン1(アルギオープ・トリファシアタ)
SSALFNAGVLNASNIDTLGSRVLSALLNGVSSAAQGLGINVDSGSVQSDISSSSSFLSTSSSSASYSQASASSTSGAGYTGPSGPSTGPSGYPGPLGGGAPFGQSGFGGSDGPQGGFGATGGASAGLISRVANALANTSTLRTVLRTGVSQQIASSVVQRAAQSLASTLGVDGNNLARFAVQAVSRLPAGSDTSAYAQAFSSALFNAGVLNASNIDTLGSRVLSALLNGVSSAAQGLGINVDSGSVQSDISSSSSFLSTSSSSASYSQASASSTSGAGYTGPSGPSTGPSGYPGLLGGGAPFGQSGFGGSDGPQGGFGATGGASAGLISRVANALANTSTLRTVLRTGVSQQIASSVVQRAAQSLASTLGVDGNNLARFAVQAVSRLPAGSDTSAYAQAFSSALFNAGVLNASNIDTLGSRVLSALLNGVSSAAQGLGINVDSGSVQSDISSSSSFLSTSSSSASYSQASASSTSGAGYTGPSGPSTGPSGYPGPLGGGAPFGQSGFGGSDGPQGGFGATGGASAGLISRVANALANTSTLRTVLRTGVSQQIASSVVQRAAQSLASTLGVDGNNLARFAVQAVSRLPAGSDTSAYAQAFSSALFNAGVLNASNIDTLGSRVLSALLNGVSSAAQGLGINVDSGSVQSDISSSSSFLSTSSSSASYSQASASSTSGAGYTGPSGPSTGPSGYPGPLGGGAPFGQSGFGGSAGPQGGFGATGGASAGLISRVANALANTSTLRTVLRTGVSQQIASSVVQRAAQSLASTLGVDGNNLARFAVQAVSRLPAGSDTSAYAQAFSSALFNAGVLNASNIDTLGSRVLSALLNGVSSAAQGLGINVDSGSVQSDISSSSSFLSTSSSSASYSQASASSTSGAGYTGPSGPSTGPSGYPGPLGGGAPFGQSGFGGSAGPQGGFGATGGASAGLISRVANALANTSTLRTVLRTGVSQQIASSVVQRAAQSLASTLGVDGNNLARFAVQAVSRLPAGSDTSAYAQAFSSALFNAGVLNASNIDTLGSRVLSALLNGVSSAAQGLGINVDSGSVQSDISSSSSFLSTSSSSASYSQASASSTSGTGYTGPSGPSTGPSGYPGPLGGGAPFGQSGFGGSAGPQGGFGATGGASAGLISRVANALANTSTLRTVLRTGVSQQIASSVVQRAAQSLASTLGVDGNNLARFAVQAVSRLPAGSDTSAYAQAFSSALFNAGVLNASNIDTLGSRVLSALLNGVSSAAQGLGINVDSGSVQSDISSSSSFLSTSSSSASYSQASASSTSGAGYTGPSGPSTGPSGYPGPLGGGAPFGQSGFGGSAGPQGGFGATGGASAGLISRVANALANTSTLRTVLRTGVSQQIASSVVQRAAQSLASTLGVDGNNLARFAVQAVSRLPAGSDTSAYAQAFSSALFNAGVLNASNIDTLGSRVLSALLNGVSSAAQGLGINVDSGSVQSDISSSSSFLSTSSSSASYSQASASSTSGAGYTGPSGPSTGPSGYPGPLGGGAPFGQSGFGGSDGPQGGFGATGGASAGLISRVANALANTSTLRTVLRTGVSQQIASSVVQRAAQSLASTLGVDGNNLARFAVQAVSRLPAGSDTSAYAQAFSSALFNAGVLNASNIDTLGSRVLSALLNGVSSAAQGLGINVDSGSVQSDISSSSSFLSTSSSSASYSQASASSTSGAGYTGPSGPSTGPSGYPGPLGGGAPFGQSGFGGSAGPQGGFGATGGASAGLISRVANALANTSTLRTVLRTGVSQQIASSVVQRAAQSLASTLGVDGNNLARFAVQAVSRLPAGSDTSAYAQAFSSALFNAGVLNASNIDTLGSRVLSALLNGVSSAAQGLGINVDSGSVQSDISSSSSFLSTSSSSASYSQASASSTSGAGYTGPSGPSTGPSGYPGPLGGGAPFGQSGFGGSAGPQGGFGATGGASAGLISRVANALANTSTLRTVLRTGVSQQIASSVVQRAAQSLASTLGVDGNNLARFAVQAVSRLPAGSDTSAYAQAFSSALFNAGVLNASNIDTLGSRVLSALLNGVSSAAQGLGINVDSGSVQSDISSSSSFLSTSSSSASYSQASASSTSGAGYTGPSGPSTGPSGYPGPLGGGAPFGQSGFGGSAGPQGGFGATGGASAGLISRVANALANTSTLRTVLRTGVSQQIASSVVQRAAQSLASTLGVDGNNLARFAVQAVSRLPAGSDTSAYAQAFSSALFNAGVLNASNIDTLGSRVLSALLNGVSSAAQGLGINVDSGSVQSDISSSSSFLSTSSSSASYSQASASSTSGAGYTGPSGPSTGPSGYPGPLGGGAPFGQSGFGGSAGPQGGFGATGGASAGLISRVANALANTSTLRTVLRTGVSQQIASSVVQRAAQSLASTLGVDGNNLARFAVQAVSRLPAGSDTSAYAQAFSSALFNAGVLNASNIDTLGSRVLSALLNGVSSAAQGLGINVDSGSVQSDISSSSSFLSTSSSSASYSQALASSTSGAGYTGPSGPSTGPSGYPGPLGGGAPFGQSGFGGSAGPQGGFGATGGASAGLISRVANALANTSTLRTVLRTGVSQQIASSVVQRAAQSLASTLGVDGNNLARFAVQAVSRLPAGSDTSAYAQAFSSALFNAGVLNASNIDTLGSRVLSALLNGVSSAAQGLGINVDSGSVQSDISSSSSFLSTSSSSASYSQASASSTSGAGYTGPSGPSTGPSGYPGPLSGGASFGSGQSSFGQTSAFSASGAGQSAGVSVISSLNSPVGLRSASAASRLSQLTSSITNAVGANGVDANSLARSLQSSFSALRSSGMSSSDAKIEVLLETIVGLLQLLSNTQVRGVNPATASSVANSAARSFELVLA
小管状スピドロイン
配列番号91:
>gi|63054371|gb|AAY28953.1|小管状スピドロイン1(アルギオープ・アウランチア)
GNAAGLGNALSQAVSSVGVGASSSTYANAVSNAVGQFLAGQGILNXANAGSLASSFASALSASAASVASSAAAQXASQSQAAASAFSRAASQSASQSAARSGAQSSSXTTTTSTSGSQAASQSASSAASQA
配列番号92:
>gi|61387231|gb|AAX45291.1|小管状スピドロイン(アルギオープ・アウランチア)
TTTSTAGSQAASQFASSAASQASASSFARASSASLAASSSFSSAFSSANSLSALGNVGYQLGFNVANNLGIGNAAGLGNALSQAVSSVGVGASSSSYANAVSNAVGQLLAGQGILNAANAGSLASSFASALSASAASVASSAAAQAASQSQAAASAFSRAASQSASQSAARSGAQSISTTTTTSTAGSQAASQSASSAASQASASSFARASSASLAASSSFSSAFSSANSLSALGNVGYQLGFNVANNLGIGNAAGLGNALSQAVSSVGVGASSSTYANAVSNAVGQFLAGQGILNAANAGSLASSFASALSASAASVASSAAAQAASQSQAAASAFSRAASQSASQSAARSGAQSSSTTTTTSTAGSQAASQFASSAASQASASSFARASSASLAASSSFSSAFSSANSLSALGNVGYQLGFNVANNLGISNAAGLGNALSQAVSSVGVGASSSSYANAVSNAVGQFLAGQGILNAANAGSLASSFASALSASAASVASSAAAQAASQSQAAASAFSRAASQSASQSAARSGAQSSSTTTTTST
配列番号93:
>gi|61387234|gb|AAX45292.1|小管状スピドロイン(アルギオープ・アウランチア)
STYANAVSNAVGQFLAGQGILNAANAGSLASSFASALSASAASVASSAAAQAASQSQAAASAFSRAASQSASQSAARSGAQSFSTTTTTSTAGSQAASQSASSAASQASASSFARASSASLAASSAFSSAFSSANSLSALGNVAYQLGFNVANTLGIGNAAGLGNALSQAVSSVGVGASSSTYANAVSNAVGQFLAGQGVLNAGNAGSLASSFANALSNSALSVGSRVSSPSYGALSPIAAGPNFISTGLNVGGPFTTLSQSLPTSLQTALAPIVSSSGLGSSAATARVRSLANSIASAISSSGGSLSVPAFLNLLSSVGAQVSSSSSLNSSEVTNEVLLEAIAALLQVINGGSITSVDLRNVPNAQQDLVNALSG
配列番号94:
>gi|61387237|gb|AAX45293.1|小管状スピドロイン(アラネウス・ゲモイデス(Araneus gemmoides))
ASQSQAASQSQAAASAFRQAASQSASQSASRAGSQSSTKTTSTSTSGSQADSRSASSSASQASASAFAQQSSASLSSSSSFSSAFSSATSISAVGNVGYQLGLKVANSLGLGNAQALASSLSQAVSAVGVGASSNAYANAVSNAVGQVLAGQGILNAANAGSLASSFASALSSSAASVASQSASQSQAASQSQAAASAFRQAASQSASQSASRAGSQSSTKTTSTSTSGSQADSRSASSSASQASASAFAQQSSASLSSSSSFSSAFSSATSISAVGNVGYQLGLKVANSLGLGNAQALASSLSQAVSAVGVGASSNAYANAVSNAVGQVLAGQGILNAANAGSLASSFASALSSSAASVASQSASQSQAASQSQAAASAFRQAASQSASQSDSRAGSQSSTKTTSTSTSGSQADSRSASSSASQASASAFAQQSSASLSSSSSFSSAFSSATSISAVGNVGYQLGLKVANSLGLGNAQALASSLSQAVSAVGVGASSNAYANAVSNAVGQVLAGQGILNAANAGSLASSFASALSSSAASVASQSASQSQAASQSQAAASAFRQAASQSASQSASRAGSQSSTKTTSTSTSGSQADSRSASSSASQASASAFAQQSSASLSSSSSFSSAFSSATSISAVGNVGYQLGLKVANS
配列番号95:
>gi|61387241|gb|AAX45294.1|小管状スピドロイン(アラネウス・ゲモイデス)
SASQSQAAASAFRQAASQSASQSASRAGSQSSSKTTSTSTSGSQADSRSASSSASQASASAIAQQSSASLSSSSSFSSAFSSATSLSAVGNVGYQLGLKVANSLGLGNAQALASQGILNAANAGSLASSFASALSASAGSVGNRSSAGPSAVGLGGVSAVPGFISATPVVGGPVTVNGQVLPAALQTALAPVVTSSGLASSAASARVSSLAQSIASAISSSGGTLSVPIFLNLLSSAGAQATASSSLSSSQVTSQVLLEGIAALLQVINGAQIRSVNLANVPNVQQALVSALSG
配列番号96:
>gi|61387244|gb|AAX45295.1|小管状スピドロイン(アメリカジョロウグモ)
ASAASSLAYSIGISAARSLGIADAAGLAGALARAAGALGQGDTAASYGNALSTAAGQFFATAGLLNAGNASALASSFARAFSASAESQSFAQSQAFQQASAFQQAASRSASQSAAEADSTSSSTTTTTSAARSQAASQSASSSYSSAFAQAASSSFAISSALSRAFSSVSSASAASSLAYSIGLSAARSLGIADATGLAGALARAVGALGQGATAASYGNALSTAAAQFFATAGLLNAGNASALASSFARAFSASAESQSFAQSQAFQQASAFQQAASRSASQSAAEAGSTSSSTTTTTSAARSQAASQSASSSYSSAFAQAASSSLATSSALSRAFSSVSSASAASSLAYSIGLSAARSLGIADAAGLAGVLARAAGALGQGATAASYGNALSTAAGQFFAAQGLLNAGNVSSLASALANALSYSAANSAASGNYIGVSQNFGSIAPVAGTAGISVGVPGLLPTSAGTVLAPANAQIIAPGLQTTLAPVFSSSGLSSASANARVSSLAQSFASALSASRGTLSVSTFLTLLSPISSQIRANTSLDGTQATVQVLLEALAALLQVINAAQITEVNVSNVSSANAALVSALAG
Claims (41)
- 化合物が装填されたスパイダーシルク粒子を製造する方法であって、
i)少なくとも2つの同一の反復単位を含むスパイダーシルクポリペプチドを1つ又は複数含むスパイダーシルク粒子を準備する工程と、
ii)前記スパイダーシルク粒子を、水溶性であり、50Da〜20kDaの分子量を有する少なくとも1つの化合物とインキュベートする工程と、
を含む、化合物が装填されたスパイダーシルク粒子を製造する方法。 - 工程i)で準備する該スパイダーシルク粒子を、
a)少なくとも2つの同一の反復単位を含むスパイダーシルクポリペプチドを1つ又は複数含む水溶液を準備する工程と、
b)該スパイダーシルクポリペプチドの凝集を誘起し、スパイダーシルク粒子を形成する、誘起する工程と、
c)該スパイダーシルク粒子を相分離により分離する工程と、
により作製する、請求項1に記載の方法。 - 化合物が該スパイダーシルク粒子のマトリクスに浸透することが可能である、請求項1又は2に記載の方法。
- 装填された化合物の少なくとも40%、又は少なくとも50%、60%、70%、80%、90%若しくは95%が該スパイダーシルク粒子のマトリクス内に位置する、請求項1〜3のいずれか一項に記載の方法。
- スパイダーシルク粒子が、0.1μm〜500μm、又は0.1μm〜100μm、又は0.2μm〜20μm、又は0.2μm〜1μm、又は0.25μm〜0.7μmのメジアン径を有する、請求項1〜4のいずれか一項に記載の方法。
- 少なくとも2つの同一の反復単位は、各々が、
i)GPGXX(配列番号3)(ここでXは任意のアミノ酸であり、又はそれぞれの場合で独立してA、S、G、Y、P及びQからなる群から選択される)、
ii)GGX(ここでXは任意のアミノ酸であり、又はそれぞれの場合で独立してY、P、R、S、A、T、N及びQからなる群から選択される)、及び
iii)Ax(ここでxは5〜10の整数である)
からなる群から選択されるコンセンサス配列を少なくとも1つ含む、請求項1〜5のいずれか一項に記載の方法。 - スパイダーシルクポリペプチドそれぞれの反復単位が独立して、モジュールA(配列番号20)若しくはその変異体、モジュールC(配列番号21)若しくはその変異体、モジュールQ(配列番号22)若しくはその変異体、モジュールAC(配列番号29)、モジュールAK(配列番号30)、モジュールCC(配列番号31)、モジュールCK1(配列番号32)、モジュールCK2(配列番号33)、又はモジュールCKC(配列番号34)から選択される、請求項6に記載の方法。
- スパイダーシルクポリペプチドが非反復(NR)単位を更に少なくとも1つ含む、請求項7に記載の方法。
- 非反復(NR)単位が独立して、NR3(配列番号41及び配列番号45)又はその変異体、及びNR4(配列番号42及び配列番号46)又はその変異体からなる群から選択される、請求項8に記載の方法。
- スパイダーシルクポリペプチドが、ADF−3(配列番号1及び配列番号47)、ADF−4(配列番号2及び配列番号48)、MaSp I(配列番号43及び配列番号53〜配列番号64)、MaSp II(配列番号44及び配列番号65〜配列番号78)、(C)mNRz、NRz(C)m、(AQ)nNRz、NRz(AQ)n、NRz(QAQ)o、(QAQ)oNRz、(C)m、(AQ)n、及び(QAQ)o(ここで、mは8〜48の整数であり、nは6〜24の整数であり、oは8〜16の整数であり、zは1〜3の整数である)からなる群から選択される、請求項1〜9のいずれか一項に記載の方法。
- スパイダーシルクポリペプチドが、C16、C32、(AQ)12、(AQ)24、C16NR4、C32NR4、(AQ)12NR3、又は(AQ)24NR3である、請求項10に記載の方法。
- 水溶液中の該スパイダーシルクポリペプチドの濃度が、0.1wt%/vol〜30wt%/vol、又は1wt%/vol〜20wt%/volである、請求項2〜11のいずれか一項に記載の方法。
- 凝集が、pHシフト、イオン交換、せん断力、アルコール若しくはリオトロピック塩の添加により又はそれらの組み合わせにより誘起される、請求項2〜12に記載の方法。
- アルコールがメタノールである、請求項13に記載の方法。
- リオトロピック塩が、硫酸アンモニウム、リン酸ナトリウム及びリン酸カリウムからなる群から選択される、請求項13に記載の方法。
- リオトロピック塩の濃度が約400mM〜約3M、又は約1M〜約2M、又は約2Mである、請求項13又は15に記載の方法。
- 化合物が、薬学的に活性のある化合物、化粧品物質、農業用物質、化学誘引物質、化学忌避物質、抗真菌物質、抗菌物質、栄養素、健康補助食品、色素、香料、又は止血剤、成長刺激剤、催炎物質、防汚剤、抗微生物剤及びUV保護剤からなる群から選択される作用物質である、請求項1〜16のいずれか一項に記載の方法。
- 化合物が全体として正の正味電荷を有する、請求項1〜17のいずれか一項に記載の方法。
- 化合物が静電相互作用及び/又は拡散によりスパイダーシルクマトリクスに浸透することが可能である、請求項1〜18のいずれか一項に記載の方法。
- 化合物が中性又はアルカリ性の性質を有する、請求項1〜19のいずれか一項に記載の方法。
- 方法の工程ii)を、4℃〜40℃、又は10℃〜30℃、又は20℃〜25℃の温度で行う、請求項1〜20のいずれか一項に記載の方法。
- 方法の工程ii)を、1〜9、又は4〜9、又は6〜8のpHで行う、請求項1〜21のいずれか一項に記載の方法。
- 水溶性であり、50Da〜20kDaの分子量を有する化合物が少なくとも1つ装填された、少なくとも2つの同一の反復単位を含むスパイダーシルクポリペプチドを少なくとも1つ含むスパイダーシルク粒子。
- 化合物が、50Da〜10kDa、又は50Da〜6kDa、又は50Da〜4kDa、又は50Da〜1kDaの分子量を有する、請求項23に記載のスパイダーシルク粒子。
- 装填された化合物の少なくとも40%、又は50%、60%、70%、80%、90%若しくは95%が該スパイダーシルク粒子のマトリクス内に位置する、請求項23又は24に記載のスパイダーシルク粒子。
- 粒子のメジアン径が、0.1μm〜500μm、又は0.1μm〜100μm、又は0.2μm〜20μm、又は0.2μm〜1μm、又は0.25μm〜0.7μmである、請求項23〜25のいずれか一項に記載のスパイダーシルク粒子。
- スパイダーシルクポリペプチドが、
i)GPGXX(配列番号3)(ここでXは任意のアミノ酸であり、又はそれぞれの場合で独立してA、S、G、Y、P及びQからなる群から選択される)、
ii)GGX(ここでXは任意のアミノ酸であり、又はそれぞれの場合で独立してY、P、R、S、A、T、N及びQからなる群から選択される)、及び
iii)Ax(ここでxは5〜10の整数である)
からなる群から選択されるコンセンサス配列をそれぞれが少なくとも1つ含む少なくとも2つの同一の反復単位を含む、請求項23〜26のいずれか一項に記載のスパイダーシルク粒子。 - スパイダーシルクポリペプチドの反復単位が独立して、モジュールA(配列番号20)若しくはその変異体、モジュールC(配列番号21)若しくはその変異体、モジュールQ(配列番号22)若しくはその変異体、モジュールAC(配列番号29)、モジュールAK(配列番号30)、モジュールCC(配列番号31)、モジュールCK1(配列番号32)、モジュールCK2(配列番号33)、又はモジュールCKC(配列番号34)から選択される、請求項27に記載のスパイダーシルク粒子。
- スパイダーシルクポリペプチドが非反復(NR)単位を更に1つ又は複数含む、請求項28に記載のスパイダーシルク粒子。
- NR単位が独立して、NR3(配列番号41及び配列番号45)又はその変異体、及びNR4(配列番号42及び配列番号46)又はその変異体からなる群から選択される、請求項29に記載のスパイダーシルク粒子。
- スパイダーシルクポリペプチドが、ADF−3(配列番号1及び配列番号47)、ADF−4(配列番号2及び配列番号48)、MaSp I(配列番号43及び配列番号53〜配列番号64)、MaSp II(配列番号44及び配列番号65〜配列番号78)、(C)mNRz、NRz(C)m、(AQ)nNRz、NRz(AQ)n、NRz(QAQ)o、(QAQ)oNRz、(C)m、(AQ)n、及び(QAQ)o(ここで、mは8〜48の整数であり、nは6〜24の整数であり、oは8〜16の整数であり、zは1〜3の整数である)からなる群から選択される、請求項23〜30のいずれか一項に記載のスパイダーシルク粒子。
- スパイダーシルクポリペプチドが、C16、C32、(AQ)12、(AQ)24、C16NR4、C32NR4、(AQ)12NR3、又は(AQ)24NR3である、請求項31に記載のスパイダーシルク粒子。
- 化合物が、薬学的に活性のある化合物、化粧品物質、農業用物質、化学誘引物質、化学忌避物質、抗真菌物質、抗菌物質、栄養素、健康補助食品、色素、香料、又は止血剤、成長刺激剤、催炎物質、防汚剤、抗微生物剤及びUV保護剤からなる群から選択される作用物質である、請求項23〜32のいずれか一項に記載のスパイダーシルク粒子。
- 化合物が全体として正の正味電荷を有する、請求項23〜33のいずれか一項に記載のスパイダーシルク粒子。
- 化合物が静電相互作用及び/又は拡散によりスパイダーシルクマトリクスに浸透することが可能である、請求項23〜34のいずれか一項に記載のスパイダーシルク粒子。
- 化合物が中性又はアルカリ性の性質を有する、請求項23〜35のいずれか一項に記載のスパイダーシルク粒子。
- 化合物が生理学的条件への曝露の際に拡散により該スパイダーシルク粒子から放出される、請求項23〜36のいずれか一項に記載のスパイダーシルク粒子。
- 化合物の20%未満、又は15%未満、又は10%未満が最初の24時間以内に放出される、請求項37に記載のスパイダーシルク粒子。
- 請求項33〜38のいずれか一項に記載のスパイダーシルク粒子と、付加的に薬学的に許容可能な緩衝剤、希釈剤及び/又は賦形剤とを含む医薬組成物であって、該医薬組成物が制御送達及び持続送達に有用であり、該化合物が薬学的に活性のある化合物である、請求項33〜38のいずれか一項に記載のスパイダーシルク粒子と、付加的に薬学的に許容可能な緩衝剤、希釈剤及び/又は賦形剤とを含む医薬組成物。
- 制御送達及び持続送達のための請求項33〜38のいずれか一項に記載のスパイダーシルク粒子を含む化粧品組成物であって、該化合物が化粧品化合物である、制御送達及び持続送達のための請求項33〜38のいずれか一項に記載のスパイダーシルク粒子を含む化粧品組成物。
- 化合物が装填されたスパイダーシルク粒子であって、該化合物が水溶性であり、50Da〜20kDaの分子量を有し、全体として正の正味電荷を有し、該スパイダーシルク粒子が少なくとも2つの同一の反復単位を含むスパイダーシルクポリペプチドを1つ又は複数含み、該粒子が請求項1〜22のいずれか一項に記載の方法により取得可能である、化合物が装填されたスパイダーシルク粒子。
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JP2017007999A (ja) * | 2015-06-25 | 2017-01-12 | 花王株式会社 | 美白剤 |
WO2018159695A1 (ja) * | 2017-02-28 | 2018-09-07 | 学校法人慶應義塾 | 微生物増殖抑制剤、微生物の増殖を抑制する方法、耐紫外線性向上剤、耐紫外線性を向上させる方法、人工タンパク質成形体及びその製造方法、人工タンパク質溶液、並びに、着色剤 |
WO2020241769A1 (ja) * | 2019-05-29 | 2020-12-03 | Spiber株式会社 | 構造タンパク質微小体及びその製造方法、ナノファイバーの製造方法、並びにタンパク質構造体の製造方法 |
JPWO2020241769A1 (ja) * | 2019-05-29 | 2021-12-16 | Spiber株式会社 | 構造タンパク質微小体及びその製造方法、ナノファイバーの製造方法、並びにタンパク質構造体の製造方法 |
JP7007008B2 (ja) | 2019-05-29 | 2022-02-10 | Spiber株式会社 | 構造タンパク質微小体及びその製造方法、ナノファイバーの製造方法、並びにタンパク質構造体の製造方法 |
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WO2011063990A3 (en) | 2012-03-29 |
WO2011063990A2 (en) | 2011-06-03 |
JP5889199B2 (ja) | 2016-03-22 |
EP2506837A2 (en) | 2012-10-10 |
US9233067B2 (en) | 2016-01-12 |
US20130109762A1 (en) | 2013-05-02 |
EP2506837B1 (en) | 2020-07-01 |
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