JP2010513311A5 - - Google Patents
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- JP2010513311A5 JP2010513311A5 JP2009541599A JP2009541599A JP2010513311A5 JP 2010513311 A5 JP2010513311 A5 JP 2010513311A5 JP 2009541599 A JP2009541599 A JP 2009541599A JP 2009541599 A JP2009541599 A JP 2009541599A JP 2010513311 A5 JP2010513311 A5 JP 2010513311A5
- Authority
- JP
- Japan
- Prior art keywords
- isolated polypeptide
- amino acid
- group
- acid sequence
- polypeptide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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- 108090000765 processed proteins & peptides Proteins 0.000 claims description 167
- 229920001184 polypeptide Polymers 0.000 claims description 166
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 166
- 150000001413 amino acids Chemical class 0.000 claims description 85
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 61
- -1 t-butoxycarbonyl Chemical group 0.000 claims description 28
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 24
- 239000000816 peptidomimetic Substances 0.000 claims description 21
- 125000006239 protecting group Chemical group 0.000 claims description 20
- 239000000203 mixture Substances 0.000 claims description 18
- 235000012000 cholesterol Nutrition 0.000 claims description 12
- 230000000694 effects Effects 0.000 claims description 12
- 239000003937 drug carrier Substances 0.000 claims description 10
- 201000001320 Atherosclerosis Diseases 0.000 claims description 9
- 210000004899 c-terminal region Anatomy 0.000 claims description 9
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 6
- 150000003904 phospholipids Chemical class 0.000 claims description 6
- 230000006641 stabilisation Effects 0.000 claims description 6
- 238000011105 stabilization Methods 0.000 claims description 6
- 208000024891 symptom Diseases 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 230000000087 stabilizing effect Effects 0.000 claims description 5
- 229910052727 yttrium Inorganic materials 0.000 claims description 5
- WTKQMHWYSBWUBE-UHFFFAOYSA-N (3-nitropyridin-2-yl) thiohypochlorite Chemical group [O-][N+](=O)C1=CC=CN=C1SCl WTKQMHWYSBWUBE-UHFFFAOYSA-N 0.000 claims description 4
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 4
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 4
- 125000006181 4-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])C([H])([H])* 0.000 claims description 4
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 150000001408 amides Chemical class 0.000 claims description 4
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 4
- 125000002933 cyclohexyloxy group Chemical group C1(CCCCC1)O* 0.000 claims description 4
- 239000003446 ligand Substances 0.000 claims description 4
- 150000002632 lipids Chemical class 0.000 claims description 4
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 claims description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 229940124597 therapeutic agent Drugs 0.000 claims description 4
- 101150092476 ABCA1 gene Proteins 0.000 claims description 3
- 102000055510 ATP Binding Cassette Transporter 1 Human genes 0.000 claims description 3
- 108700005241 ATP Binding Cassette Transporter 1 Proteins 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 208000035475 disorder Diseases 0.000 claims description 3
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 claims description 2
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 claims description 2
- WSNDAYQNZRJGMJ-UHFFFAOYSA-N 2,2,2-trifluoroethanone Chemical compound FC(F)(F)[C]=O WSNDAYQNZRJGMJ-UHFFFAOYSA-N 0.000 claims description 2
- CBEFMGJHEKAMNI-UHFFFAOYSA-N 9-oxofluorene-1-carboxylic acid Chemical group C12=CC=CC=C2C(=O)C2=C1C=CC=C2C(=O)O CBEFMGJHEKAMNI-UHFFFAOYSA-N 0.000 claims description 2
- HTPXFGUCAUTOEL-UHFFFAOYSA-N 9h-fluorene-1-carboxylic acid Chemical group C1C2=CC=CC=C2C2=C1C(C(=O)O)=CC=C2 HTPXFGUCAUTOEL-UHFFFAOYSA-N 0.000 claims description 2
- DNVJGJUGFFYUPT-UHFFFAOYSA-N 9h-fluorene-9-carboxylic acid Chemical group C1=CC=C2C(C(=O)O)C3=CC=CC=C3C2=C1 DNVJGJUGFFYUPT-UHFFFAOYSA-N 0.000 claims description 2
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 2
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 2
- 102000004190 Enzymes Human genes 0.000 claims description 2
- 108090000790 Enzymes Proteins 0.000 claims description 2
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 2
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 2
- 206010061218 Inflammation Diseases 0.000 claims description 2
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 2
- 102000006830 Luminescent Proteins Human genes 0.000 claims description 2
- 108010047357 Luminescent Proteins Proteins 0.000 claims description 2
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 claims description 2
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 claims description 2
- 229930003427 Vitamin E Natural products 0.000 claims description 2
- DFPAKSUCGFBDDF-ZQBYOMGUSA-N [14c]-nicotinamide Chemical compound N[14C](=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-ZQBYOMGUSA-N 0.000 claims description 2
- 239000012190 activator Substances 0.000 claims description 2
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 2
- 229940127218 antiplatelet drug Drugs 0.000 claims description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 2
- 239000003613 bile acid Substances 0.000 claims description 2
- 239000011230 binding agent Substances 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 claims description 2
- 239000000975 dye Substances 0.000 claims description 2
- 239000007850 fluorescent dye Substances 0.000 claims description 2
- 238000009472 formulation Methods 0.000 claims description 2
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims description 2
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims description 2
- 238000000338 in vitro Methods 0.000 claims description 2
- 230000004054 inflammatory process Effects 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 229910052751 metal Inorganic materials 0.000 claims description 2
- 239000002184 metal Substances 0.000 claims description 2
- 239000007800 oxidant agent Substances 0.000 claims description 2
- 230000003647 oxidation Effects 0.000 claims description 2
- 238000007254 oxidation reaction Methods 0.000 claims description 2
- 239000002245 particle Substances 0.000 claims description 2
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 2
- 229910052698 phosphorus Inorganic materials 0.000 claims description 2
- 239000000106 platelet aggregation inhibitor Substances 0.000 claims description 2
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 239000002096 quantum dot Substances 0.000 claims description 2
- 238000012216 screening Methods 0.000 claims description 2
- 230000002194 synthesizing effect Effects 0.000 claims description 2
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims description 2
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims description 2
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 235000019165 vitamin E Nutrition 0.000 claims description 2
- 229940046009 vitamin E Drugs 0.000 claims description 2
- 239000011709 vitamin E Substances 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 230000001771 impaired effect Effects 0.000 claims 1
- 238000000034 method Methods 0.000 description 35
- 241000124008 Mammalia Species 0.000 description 18
- 150000008574 D-amino acids Chemical class 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US87490906P | 2006-12-13 | 2006-12-13 | |
| PCT/US2007/087477 WO2008115303A2 (en) | 2006-12-13 | 2007-12-13 | Potent and selective mediators of cholesterol efflux |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2010513311A JP2010513311A (ja) | 2010-04-30 |
| JP2010513311A5 true JP2010513311A5 (enExample) | 2011-02-03 |
Family
ID=39766652
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009541599A Pending JP2010513311A (ja) | 2006-12-13 | 2007-12-13 | コレステロール流出の強力かつ選択的なメディエータ |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US8987192B2 (enExample) |
| EP (1) | EP2121746B1 (enExample) |
| JP (1) | JP2010513311A (enExample) |
| CN (1) | CN101675072A (enExample) |
| AT (1) | ATE533783T1 (enExample) |
| AU (1) | AU2007349237B2 (enExample) |
| CA (1) | CA2672131C (enExample) |
| DK (1) | DK2121746T3 (enExample) |
| ES (1) | ES2377329T3 (enExample) |
| WO (1) | WO2008115303A2 (enExample) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2011101536A (ru) | 2008-06-18 | 2012-07-27 | Дзе Риджентс Оф Дзе Юниверсити Оф Калифорниа (Us) | Усовершенствованные пептидные медиаторы оттока холестерина |
| EP2517013A4 (en) * | 2009-12-23 | 2013-07-17 | Artery Therapeutics Inc | DIAGNOSIS AND TREATMENT OF DISEASES ASSOCIATED WITH DEFICIENT REVERSE CHOLESTER INTRANSPORT |
| WO2011139819A2 (en) * | 2010-04-28 | 2011-11-10 | The Regents Of The University Of California | Creation of oxidation-resistant hdl mimetic peptides |
| CN105050614B (zh) * | 2013-03-15 | 2019-04-05 | 加利福尼亚大学董事会 | 刺激胆固醇流出的具有降低的毒性的肽 |
| US11091529B2 (en) * | 2014-09-17 | 2021-08-17 | The Regents Of The University Of California | Peptides having reduced toxicity that stimulate cholesterol efflux |
| CN112442114A (zh) | 2019-08-29 | 2021-03-05 | 渥太华Hdl药物研发公司 | 一种多肽及其应用 |
| CN112511569B (zh) * | 2021-02-07 | 2021-05-11 | 杭州筋斗腾云科技有限公司 | 网络资源访问请求的处理方法、系统及计算机设备 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE60035163T2 (de) | 1999-03-15 | 2008-02-21 | University Of British Columbia, Vancouver | Abc1 polypeptide und verfahren und reagenzien zur modulation des cholesterolgehalts |
| CA2405870A1 (en) * | 2000-04-06 | 2001-10-18 | Kos Pharmaceuticals, Inc. | Compounds and methods for lowering cholesterol levels without inducing hypertriglyceridemia |
| US6664230B1 (en) * | 2000-08-24 | 2003-12-16 | The Regents Of The University Of California | Orally administered peptides to ameliorate atherosclerosis |
| US7199102B2 (en) | 2000-08-24 | 2007-04-03 | The Regents Of The University Of California | Orally administered peptides synergize statin activity |
| US7691965B2 (en) | 2002-05-08 | 2010-04-06 | The Regents Of The University Of California | Helical synthetic peptides that stimulate cellular cholesterol efflux |
| BRPI0513402A (pt) | 2004-07-16 | 2008-05-06 | Tufts College | miméticos de apolipoproteìna a1 e usos dos mesmos |
| US8541236B2 (en) | 2006-12-08 | 2013-09-24 | University Of Washington | Mutant apolipoprotein A-1 polypeptide with increased resistance to oxidation and reactive carbonyls |
-
2007
- 2007-12-13 CA CA2672131A patent/CA2672131C/en not_active Expired - Fee Related
- 2007-12-13 WO PCT/US2007/087477 patent/WO2008115303A2/en not_active Ceased
- 2007-12-13 AT AT07874411T patent/ATE533783T1/de active
- 2007-12-13 CN CN200780046286A patent/CN101675072A/zh active Pending
- 2007-12-13 JP JP2009541599A patent/JP2010513311A/ja active Pending
- 2007-12-13 ES ES07874411T patent/ES2377329T3/es active Active
- 2007-12-13 DK DK07874411.7T patent/DK2121746T3/da active
- 2007-12-13 EP EP07874411A patent/EP2121746B1/en not_active Not-in-force
- 2007-12-13 US US12/519,116 patent/US8987192B2/en active Active
- 2007-12-13 AU AU2007349237A patent/AU2007349237B2/en not_active Ceased
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