NO313098B1 - Rettkjedete eller sykliske oligopeptider med affinitet for opioidreseptorer, samt farmasöytisk preparat og anvendelse avpeptidene - Google Patents
Rettkjedete eller sykliske oligopeptider med affinitet for opioidreseptorer, samt farmasöytisk preparat og anvendelse avpeptidene Download PDFInfo
- Publication number
- NO313098B1 NO313098B1 NO19951990A NO951990A NO313098B1 NO 313098 B1 NO313098 B1 NO 313098B1 NO 19951990 A NO19951990 A NO 19951990A NO 951990 A NO951990 A NO 951990A NO 313098 B1 NO313098 B1 NO 313098B1
- Authority
- NO
- Norway
- Prior art keywords
- leu
- tyr
- phe
- glu
- cyclo
- Prior art date
Links
- 102000015636 Oligopeptides Human genes 0.000 title claims description 41
- 108010038807 Oligopeptides Proteins 0.000 title claims description 41
- 102000003840 Opioid Receptors Human genes 0.000 title claims description 23
- 108090000137 Opioid Receptors Proteins 0.000 title claims description 23
- 125000004122 cyclic group Chemical group 0.000 title claims description 18
- 239000000825 pharmaceutical preparation Substances 0.000 title claims description 4
- 108090000765 processed proteins & peptides Proteins 0.000 title description 29
- 102000004196 processed proteins & peptides Human genes 0.000 title description 19
- 102000005962 receptors Human genes 0.000 claims description 14
- 108020003175 receptors Proteins 0.000 claims description 14
- 235000001014 amino acid Nutrition 0.000 claims description 13
- 150000001413 amino acids Chemical class 0.000 claims description 13
- 238000002360 preparation method Methods 0.000 claims description 11
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 7
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 claims description 5
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 claims description 4
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims description 4
- OGNSCSPNOLGXSM-VKHMYHEASA-N L-2,4-diaminobutyric acid Chemical compound NCC[C@H](N)C(O)=O OGNSCSPNOLGXSM-VKHMYHEASA-N 0.000 claims description 4
- QNAYBMKLOCPYGJ-UWTATZPHSA-N D-alanine Chemical compound C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 claims description 3
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 claims description 3
- KNYPNEYICHHLQL-ACRUOGEOSA-N Phe-Leu-Tyr Chemical compound C([C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=CC=C1 KNYPNEYICHHLQL-ACRUOGEOSA-N 0.000 claims description 3
- 150000001412 amines Chemical class 0.000 claims description 3
- 230000035939 shock Effects 0.000 claims description 3
- 230000036642 wellbeing Effects 0.000 claims description 3
- PWKSKIMOESPYIA-UHFFFAOYSA-N 2-acetamido-3-sulfanylpropanoic acid Chemical compound CC(=O)NC(CS)C(O)=O PWKSKIMOESPYIA-UHFFFAOYSA-N 0.000 claims description 2
- GYDJEQRTZSCIOI-UHFFFAOYSA-N Tranexamic acid Chemical compound NCC1CCC(C(O)=O)CC1 GYDJEQRTZSCIOI-UHFFFAOYSA-N 0.000 claims description 2
- 239000000969 carrier Substances 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- 229960003104 ornithine Drugs 0.000 claims description 2
- WPLOVIFNBMNBPD-ATHMIXSHSA-N subtilin Chemical compound CC1SCC(NC2=O)C(=O)NC(CC(N)=O)C(=O)NC(C(=O)NC(CCCCN)C(=O)NC(C(C)CC)C(=O)NC(=C)C(=O)NC(CCCCN)C(O)=O)CSC(C)C2NC(=O)C(CC(C)C)NC(=O)C1NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C1NC(=O)C(=C/C)/NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C2NC(=O)CNC(=O)C3CCCN3C(=O)C(NC(=O)C3NC(=O)C(CC(C)C)NC(=O)C(=C)NC(=O)C(CCC(O)=O)NC(=O)C(NC(=O)C(CCCCN)NC(=O)C(N)CC=4C5=CC=CC=C5NC=4)CSC3)C(C)SC2)C(C)C)C(C)SC1)CC1=CC=CC=C1 WPLOVIFNBMNBPD-ATHMIXSHSA-N 0.000 claims description 2
- 208000020401 Depressive disease Diseases 0.000 claims 1
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims 1
- 125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 claims 1
- 208000026251 Opioid-Related disease Diseases 0.000 claims 1
- 230000000694 effects Effects 0.000 description 20
- 239000012634 fragment Substances 0.000 description 19
- 102000002265 Human Growth Hormone Human genes 0.000 description 16
- 108010000521 Human Growth Hormone Proteins 0.000 description 16
- 239000000854 Human Growth Hormone Substances 0.000 description 16
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
- 238000012360 testing method Methods 0.000 description 13
- 230000027455 binding Effects 0.000 description 12
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 10
- 102000004142 Trypsin Human genes 0.000 description 10
- 108090000631 Trypsin Proteins 0.000 description 10
- 239000012588 trypsin Substances 0.000 description 10
- 210000003169 central nervous system Anatomy 0.000 description 9
- 238000004128 high performance liquid chromatography Methods 0.000 description 8
- 102000004190 Enzymes Human genes 0.000 description 7
- 108090000790 Enzymes Proteins 0.000 description 7
- 102000018997 Growth Hormone Human genes 0.000 description 7
- 108010051696 Growth Hormone Proteins 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 238000003556 assay Methods 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
- 239000000122 growth hormone Substances 0.000 description 7
- 239000011347 resin Substances 0.000 description 7
- 229920005989 resin Polymers 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000003446 ligand Substances 0.000 description 6
- 229940127240 opiate Drugs 0.000 description 6
- HPZJMUBDEAMBFI-WTNAPCKOSA-N (D-Ala(2)-mephe(4)-gly-ol(5))enkephalin Chemical compound C([C@H](N)C(=O)N[C@H](C)C(=O)NCC(=O)N(C)[C@@H](CC=1C=CC=CC=1)C(=O)NCCO)C1=CC=C(O)C=C1 HPZJMUBDEAMBFI-WTNAPCKOSA-N 0.000 description 5
- 108700022183 Ala(2)-MePhe(4)-Gly(5)- Enkephalin Proteins 0.000 description 5
- 241000700199 Cavia porcellus Species 0.000 description 5
- 102000001189 Cyclic Peptides Human genes 0.000 description 5
- 108010069514 Cyclic Peptides Proteins 0.000 description 5
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 5
- 229920005654 Sephadex Polymers 0.000 description 5
- 239000012507 Sephadex™ Substances 0.000 description 5
- 239000005557 antagonist Substances 0.000 description 5
- 210000003405 ileum Anatomy 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 239000000523 sample Substances 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 4
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 230000029087 digestion Effects 0.000 description 4
- 229940063135 genotropin Drugs 0.000 description 4
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 102000005593 Endopeptidases Human genes 0.000 description 3
- 108010059378 Endopeptidases Proteins 0.000 description 3
- ONBWJWYUHXVEJS-ZTYRTETDSA-N Normorphine Chemical compound C([C@@H](NCC1)[C@@H]2C=C[C@@H]3O)C4=CC=C(O)C5=C4[C@@]21[C@H]3O5 ONBWJWYUHXVEJS-ZTYRTETDSA-N 0.000 description 3
- 239000000556 agonist Substances 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- -1 cyclic enkephalin analogues Chemical class 0.000 description 3
- 235000013922 glutamic acid Nutrition 0.000 description 3
- 239000004220 glutamic acid Substances 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 229950006134 normorphine Drugs 0.000 description 3
- 239000004031 partial agonist Substances 0.000 description 3
- 239000002287 radioligand Substances 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 238000004007 reversed phase HPLC Methods 0.000 description 3
- YFGBQHOOROIVKG-BHDDXSALSA-N (2R)-2-[[(2R)-2-[[2-[[2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]acetyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound C([C@H](C(=O)N[C@H](CCSC)C(O)=O)NC(=O)CNC(=O)CNC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=CC=C1 YFGBQHOOROIVKG-BHDDXSALSA-N 0.000 description 2
- 229920002271 DEAE-Sepharose Polymers 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 206010056438 Growth hormone deficiency Diseases 0.000 description 2
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 102400000988 Met-enkephalin Human genes 0.000 description 2
- 108010042237 Methionine Enkephalin Proteins 0.000 description 2
- 108010033276 Peptide Fragments Proteins 0.000 description 2
- 102000007079 Peptide Fragments Human genes 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 2
- 239000000730 antalgic agent Substances 0.000 description 2
- 230000008499 blood brain barrier function Effects 0.000 description 2
- 210000001218 blood-brain barrier Anatomy 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 210000001638 cerebellum Anatomy 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000004590 computer program Methods 0.000 description 2
- GCFAUZGWPDYAJN-UHFFFAOYSA-N cyclohexyl 3-phenylprop-2-enoate Chemical compound C=1C=CC=CC=1C=CC(=O)OC1CCCCC1 GCFAUZGWPDYAJN-UHFFFAOYSA-N 0.000 description 2
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 230000007515 enzymatic degradation Effects 0.000 description 2
- 238000009585 enzyme analysis Methods 0.000 description 2
- 235000019439 ethyl acetate Nutrition 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000002523 gelfiltration Methods 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 2
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 230000002797 proteolythic effect Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000000018 receptor agonist Substances 0.000 description 2
- 229940044601 receptor agonist Drugs 0.000 description 2
- 230000009291 secondary effect Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 230000000946 synaptic effect Effects 0.000 description 2
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 1
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 108010076119 Caseins Proteins 0.000 description 1
- 102000011632 Caseins Human genes 0.000 description 1
- 102100025287 Cytochrome b Human genes 0.000 description 1
- 108010075028 Cytochromes b Proteins 0.000 description 1
- XUJNEKJLAYXESH-UWTATZPHSA-N D-Cysteine Chemical group SC[C@@H](N)C(O)=O XUJNEKJLAYXESH-UWTATZPHSA-N 0.000 description 1
- IJVCSMSMFSCRME-KBQPJGBKSA-N Dihydromorphine Chemical compound O([C@H]1[C@H](CC[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O IJVCSMSMFSCRME-KBQPJGBKSA-N 0.000 description 1
- 108010092674 Enkephalins Proteins 0.000 description 1
- AFWYPMDMDYCKMD-KBPBESRZSA-N Gly-Leu-Tyr Chemical compound NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 AFWYPMDMDYCKMD-KBPBESRZSA-N 0.000 description 1
- 206010062767 Hypophysitis Diseases 0.000 description 1
- 235000019766 L-Lysine Nutrition 0.000 description 1
- 235000013878 L-cysteine Nutrition 0.000 description 1
- 239000004201 L-cysteine Substances 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- URLZCHNOLZSCCA-VABKMULXSA-N Leu-enkephalin Chemical class C([C@@H](C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)CNC(=O)CNC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=CC=C1 URLZCHNOLZSCCA-VABKMULXSA-N 0.000 description 1
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
- MQUQNUAYKLCRME-INIZCTEOSA-N N-tosyl-L-phenylalanyl chloromethyl ketone Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N[C@H](C(=O)CCl)CC1=CC=CC=C1 MQUQNUAYKLCRME-INIZCTEOSA-N 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 108010093625 Opioid Peptides Proteins 0.000 description 1
- 102000001490 Opioid Peptides Human genes 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 239000001888 Peptone Substances 0.000 description 1
- 108010080698 Peptones Proteins 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000001270 agonistic effect Effects 0.000 description 1
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 1
- 239000001099 ammonium carbonate Substances 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 150000001923 cyclic compounds Chemical class 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000002996 emotional effect Effects 0.000 description 1
- 230000006862 enzymatic digestion Effects 0.000 description 1
- 108010020477 exorphins Proteins 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000010265 fast atom bombardment Methods 0.000 description 1
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 125000005519 fluorenylmethyloxycarbonyl group Chemical group 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 238000010353 genetic engineering Methods 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 235000018977 lysine Nutrition 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- 230000000955 neuroendocrine Effects 0.000 description 1
- 239000003399 opiate peptide Substances 0.000 description 1
- 229940005483 opioid analgesics Drugs 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 108010011903 peptide receptors Proteins 0.000 description 1
- 235000019319 peptone Nutrition 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 210000003635 pituitary gland Anatomy 0.000 description 1
- 125000002924 primary amino group Chemical class [H]N([H])* 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 108010009004 proteose-peptone Proteins 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000010532 solid phase synthesis reaction Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000010183 spectrum analysis Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 235000021249 α-casein Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/61—Growth hormone [GH], i.e. somatotropin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/665—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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/10—Tetrapeptides
- C07K5/1002—Tetrapeptides with the first amino acid being neutral
- C07K5/1016—Tetrapeptides with the first amino acid being neutral and aromatic or cycloaliphatic
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Toxicology (AREA)
- Zoology (AREA)
- Psychiatry (AREA)
- Gastroenterology & Hepatology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Endocrinology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Hospice & Palliative Care (AREA)
- Addiction (AREA)
- Pain & Pain Management (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE9203496A SE9203496D0 (sv) | 1992-11-20 | 1992-11-20 | New oligopeptides |
| PCT/SE1993/000986 WO1994012532A1 (en) | 1992-11-20 | 1993-11-18 | New oligopeptides with affinity to opioid receptors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO951990L NO951990L (no) | 1995-05-19 |
| NO951990D0 NO951990D0 (no) | 1995-05-19 |
| NO313098B1 true NO313098B1 (no) | 2002-08-12 |
Family
ID=20387887
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19951990A NO313098B1 (no) | 1992-11-20 | 1995-05-19 | Rettkjedete eller sykliske oligopeptider med affinitet for opioidreseptorer, samt farmasöytisk preparat og anvendelse avpeptidene |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US5872097A (pt) |
| EP (1) | EP0745093B1 (pt) |
| JP (1) | JP3470136B2 (pt) |
| AT (1) | ATE212357T1 (pt) |
| AU (1) | AU684481B2 (pt) |
| CA (1) | CA2149899A1 (pt) |
| DE (1) | DE69331499T2 (pt) |
| DK (1) | DK0745093T3 (pt) |
| ES (1) | ES2171445T3 (pt) |
| FI (1) | FI952455A (pt) |
| NO (1) | NO313098B1 (pt) |
| NZ (1) | NZ258260A (pt) |
| PT (1) | PT745093E (pt) |
| RU (1) | RU2131438C1 (pt) |
| SE (1) | SE9203496D0 (pt) |
| WO (1) | WO1994012532A1 (pt) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU1623801A (en) * | 1999-11-19 | 2001-05-30 | Palatin Technologies, Inc. | Opioid metallopeptide compositions and methods |
| US20080045610A1 (en) * | 2004-09-23 | 2008-02-21 | Alexander Michalow | Methods for regulating neurotransmitter systems by inducing counteradaptations |
| EP1809104A4 (en) * | 2004-09-23 | 2009-04-29 | Alexander Michalow | METHODS FOR REGULATING NEUROTRANSMITTER SYSTEMS BY INDUCING COUNTER-ADAPTATIONS |
| US7454406B2 (en) * | 2005-04-29 | 2008-11-18 | Adaptec, Inc. | System and method of handling file metadata |
| SI2590992T1 (sl) * | 2010-07-09 | 2017-11-30 | The Administrators Of The Tulane Educational Fund | Analogi agonista mu opoidnega receptorja endomorfinov |
| US20160176930A1 (en) | 2010-07-09 | 2016-06-23 | The Administrators Of The Tulane Educational Fund | Mu opioid receptor agonist analogs of the endomorphins |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL8005121A (nl) * | 1979-09-20 | 1981-03-24 | Erba Farmitalia | Biologisch actieve peptiden. |
| US4254024A (en) * | 1979-10-16 | 1981-03-03 | Pennwalt Corporation | Tetrapeptides and derivatives having opiate activity |
| US4699897A (en) * | 1983-06-04 | 1987-10-13 | Amgen | Biologically active peptides structurally related to regions within growth hormones |
-
1992
- 1992-11-20 SE SE9203496A patent/SE9203496D0/xx unknown
-
1993
- 1993-11-08 US US08/433,401 patent/US5872097A/en not_active Expired - Fee Related
- 1993-11-18 DE DE69331499T patent/DE69331499T2/de not_active Expired - Fee Related
- 1993-11-18 AT AT94901120T patent/ATE212357T1/de not_active IP Right Cessation
- 1993-11-18 DK DK94901120T patent/DK0745093T3/da active
- 1993-11-18 JP JP51303594A patent/JP3470136B2/ja not_active Expired - Fee Related
- 1993-11-18 CA CA002149899A patent/CA2149899A1/en not_active Abandoned
- 1993-11-18 AU AU55816/94A patent/AU684481B2/en not_active Ceased
- 1993-11-18 ES ES94901120T patent/ES2171445T3/es not_active Expired - Lifetime
- 1993-11-18 NZ NZ258260A patent/NZ258260A/en unknown
- 1993-11-18 WO PCT/SE1993/000986 patent/WO1994012532A1/en active IP Right Grant
- 1993-11-18 RU RU95113498A patent/RU2131438C1/ru not_active IP Right Cessation
- 1993-11-18 PT PT94901120T patent/PT745093E/pt unknown
- 1993-11-18 EP EP94901120A patent/EP0745093B1/en not_active Expired - Lifetime
-
1995
- 1995-05-19 NO NO19951990A patent/NO313098B1/no not_active IP Right Cessation
- 1995-05-19 FI FI952455A patent/FI952455A/fi not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| NO951990L (no) | 1995-05-19 |
| EP0745093B1 (en) | 2002-01-23 |
| DE69331499T2 (de) | 2002-08-08 |
| NZ258260A (en) | 1996-06-25 |
| ES2171445T3 (es) | 2002-09-16 |
| FI952455A0 (fi) | 1995-05-19 |
| RU2131438C1 (ru) | 1999-06-10 |
| SE9203496D0 (sv) | 1992-11-20 |
| AU684481B2 (en) | 1997-12-18 |
| DE69331499D1 (de) | 2002-03-14 |
| AU5581694A (en) | 1994-06-22 |
| US5872097A (en) | 1999-02-16 |
| WO1994012532A1 (en) | 1994-06-09 |
| CA2149899A1 (en) | 1994-06-09 |
| EP0745093A1 (en) | 1996-12-04 |
| DK0745093T3 (da) | 2002-05-13 |
| ATE212357T1 (de) | 2002-02-15 |
| RU95113498A (ru) | 1997-03-20 |
| PT745093E (pt) | 2002-07-31 |
| FI952455A (fi) | 1995-05-19 |
| NO951990D0 (no) | 1995-05-19 |
| JPH08507748A (ja) | 1996-08-20 |
| JP3470136B2 (ja) | 2003-11-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Misicka et al. | Topographical requirements for delta opioid ligands: common structural features of dermenkephalin and deltorphin | |
| US5093233A (en) | Antagonists with position 13 modification | |
| Osakada et al. | The contractile activities of neurokinin A, B and related peptides on smooth muscles | |
| AU737057B2 (en) | Cyclic CRF antagonist peptides | |
| Balboni et al. | Opioid diketopiperazines: synthesis and activity of a prototypic class of opioid antagonists | |
| US6323312B1 (en) | Cyclic CRF antagonist peptides | |
| US20040122013A1 (en) | Analogs of nocicettin | |
| US20090149629A1 (en) | Crfr1 selective ligands | |
| EP0745093B1 (en) | New oligopeptides with affinity to opioid receptors | |
| US5736509A (en) | Cyclic peptide surface feature mimics of endothelin | |
| Griffiths et al. | Biotransformation of neuropeptides | |
| EP0341962A2 (en) | Humoral hypercalcemic factor antagonists | |
| Or et al. | Improvements in the minimum binding sequence of C5a: examination of His-67 | |
| US5087562A (en) | Humoral hypercalcemic factor antagonists with modification at position 13 . . . | |
| US4388236A (en) | Enkephalin-like compounds in bovine adrenal medulla | |
| US7141546B1 (en) | CRFR2 selective ligands | |
| WO1993025580A1 (en) | Cyclic peptides that modulate endothelin activity | |
| Zieleniak et al. | Deltorphin analogs restricted via a urea bridge: structure and opioid activity | |
| Filip et al. | Potent side‐chain to side‐chain cyclized dermorphin analogues containing a carbonyl bridge | |
| Schmidt et al. | Structural modifications of the N-terminal tetrapeptide segment of [D-Ala2] deltorphin I: effects on opioid receptor affinities and activities in vitro and on antinociceptive potency | |
| US4264492A (en) | Enkephalin-like compounds in bovine adrenal medulla | |
| Cockle et al. | Processing of the thyrotropin releasing hormone (TRH) precursor in Xenopus skin and bovine hypothalamus: evidence for the existence of extended forms of TRH | |
| US5087561A (en) | Humoral hypercalcemic factor antagonists modified at position 13 by biotin | |
| Biondi et al. | Synthesis, conformation and biological activity of dermorphin and deltorphin I analogues containing N‐alkylglycine in place of residues in position 1, 3, 5 and 6 | |
| Biondi et al. | Novel glycosylated [Lys7]‐dermorphin analogues: synthesis, biological activity and conformational investigations |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM1K | Lapsed by not paying the annual fees |