Pseudodynamic combinatorial libraries: A receptor-assisted approach for drug discovery

被引：25

作者：

Corbett, AR ^{[1
]}

Cheeseman, JD ^{[1
]}

Kazlauskas, RJ ^{[1
]}

Gleason, JL ^{[1
]}

机构：

[1] McGill Univ, Dept Chem, Montreal, PQ H3A 2K6, Canada

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2004年 / 43卷 / 18期

关键词：

combinatorial chemistry; drug design; enzyme inhibitors; kinetics; receptors;

D O I：

10.1002/anie.200453769

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Enzyme protection: An irreversible solid-phase, aqueous peptide coupling resulted in the formation of a library of eight dipeptides, while an irreversible protease-catalyzed hydrolysis destroyed them. Those dipeptides that bound to carbonic anhydrase were protected from destructions. Six cycles of active ester addition produced only the best-binding dipeptide (> 100:1) in 29% yield.

引用

收藏

页码：2432 / 2436

页数：5

相关论文

共 41 条

[1] Discovery of a potent small molecule IL-2 inhibitor through fragment assembly [J].

Braisted, AC ;

Oslob, JD ;

Delano, WL ;

Hyde, J ;

McDowell, RS ;

Waal, N ;

Yu, C ;

Arkin, MR ;

Raimundo, BC .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2003, 125 (13) :3714-3715

[2] Amplification of screening sensitivity through selective destruction: Theory and screening of a library of carbonic anhydrase inhibitors [J].

Cheeseman, JD ;

Corbett, AD ;

Shu, R ;

Croteau, J ;

Gleason, JL ;

Kazlauskas, RJ .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2002, 124 (20) :5692-5701

[3] Identification of potent and selective small-molecule inhibitors of caspase-3 through the use of extended tethering and structure-based drug design [J].

Choong, IC ;

Lew, W ;

Lee, D ;

Pham, P ;

Burdett, MT ;

Lam, JW ;

Wiesmann, C ;

Luong, TN ;

Fahr, B ;

DeLano, WL ;

McDowell, RS ;

Allen, DA ;

Erlanson, DA ;

Gordon, EM ;

O'Brien, T .

JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (23) :5005-5022

[4] Preparation of active esters on solid support for aqueous-phase peptide couplings [J].

Corbett, AD ;

Gleason, JL .

TETRAHEDRON LETTERS, 2002, 43 (08) :1369-1372

[5] Use of molecular recognition to drive chemical evolution .1. Controlling the composition of an equilibrating mixture of simple arginine receptors [J].

Eliseev, AV ;

Nelen, MI .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1997, 119 (05) :1147-1148

[6] In situ assembly of enzyme inhibitors using extended tethering [J].

Erlanson, DA ;

Lam, JW ;

Wiesmann, C ;

Luong, TN ;

Simmons, RL ;

DeLano, WL ;

Choong, IC ;

Burdett, MT ;

Flanagan, WM ;

Lee, D ;

Gordon, EM ;

O'Brien, T .

NATURE BIOTECHNOLOGY, 2003, 21 (03) :308-314

[7]

Ganesan A, 1998, ANGEW CHEM INT EDIT, V37, P2828, DOI 10.1002/(SICI)1521-3773(19981102)37:20<2828::AID-ANIE2828>3.0.CO

[8]

2-G

[9]

GANESAN A, 1998, ANGEW CHEM, V110, P2989

[10] Adaptive behavior of dynamic combinatorial libraries generated by assembly of different building blocks [J].

Grote, Z ;

Scopelliti, R ;

Severin, K .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2003, 42 (32) :3821-3825

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