Isolation of high-affinity trypsin inhibitors from a DNA-encoded chemical library

被引：90

作者：

Melkko, Samu

Zhang, Yixin

Dumelin, Christoph E.

Scheuermann, Jorg

Neri, Dario

机构：

[1] ETH, Dept Chem & Angew Biowissenschaften, CH-8093 Zurich, Switzerland

[2] ETH, Philochem AG, CH-8093 Zurich, Switzerland

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2007年 / 46卷 / 25期

关键词：

benzamidines; compound libraries; self-assembly; supramolecular chemistry; trypsin;

D O I：

10.1002/anie.200700654

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

(Chemical Equation Presented) Maturing is easy to do: Annealing benzamidine-oligonucleotide conjugates with a library of DNA-encoded compounds allows the affinity capture of pharmacophores that are capable of binding to exosites adjacent to the primary substrate-binding pocket of the serine protease trypsin. Selected conjugates show an improvement in IC50 values of several orders of magnitude compared with the starting benzamidine. © 2007 Wiley-VCH Verlag GmbH & Co. KGaA.

引用

页码：4671 / 4674

页数：4

共 18 条

[1] ENCODED COMBINATORIAL CHEMISTRY [J].

BRENNER, S ;

LERNER, RA .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (12) :5381-5383

[2] Selection of streptavidin binders firom a DNA-encoded chemical library [J].

Dumelin, CE ;

Scheuermann, J ;

Melkko, S ;

Neri, D .

BIOCONJUGATE CHEMISTRY, 2006, 17 (02) :366-370

[3] DNA-templated organic synthesis and selection of a library of macrocycles [J].

Gartner, ZJ ;

Tse, BN ;

Grubina, R ;

Doyon, JB ;

Snyder, TM ;

Liu, DR .

SCIENCE, 2004, 305 (5690) :1601-1605

[4] DNA display I. Sequence-encoded routing of DNA populations [J].

Halpin, DR ;

Harbury, PB .

PLOS BIOLOGY, 2004, 2 (07) :1015-1021

[5] DNA display III. Solid-phase organic synthesis on unprotected DNA [J].

Halpin, DR ;

Lee, JA ;

Wrenn, SJ ;

Harbury, PB .

PLOS BIOLOGY, 2004, 2 (07) :1031-1038

[6] DNA display II. Genetic manipulation of combinatorial chemistry libraries for small-molecule evolution [J].

Halpin, DR ;

Harbury, PB .

PLOS BIOLOGY, 2004, 2 (07) :1022-1030

[7] Genome sequencing in microfabricated high-density picolitre reactors [J].

Margulies, M ;

Egholm, M ;

Altman, WE ;

Attiya, S ;

Bader, JS ;

Bemben, LA ;

Berka, J ;

Braverman, MS ;

Chen, YJ ;

Chen, ZT ;

Dewell, SB ;

Du, L ;

Fierro, JM ;

Gomes, XV ;

Godwin, BC ;

He, W ;

Helgesen, S ;

Ho, CH ;

Irzyk, GP ;

Jando, SC ;

Alenquer, MLI ;

Jarvie, TP ;

Jirage, KB ;

Kim, JB ;

Knight, JR ;

Lanza, JR ;

Leamon, JH ;

Lefkowitz, SM ;

Lei, M ;

Li, J ;

Lohman, KL ;

Lu, H ;

Makhijani, VB ;

McDade, KE ;

McKenna, MP ;

Myers, EW ;

Nickerson, E ;

Nobile, JR ;

Plant, R ;

Puc, BP ;

Ronan, MT ;

Roth, GT ;

Sarkis, GJ ;

Simons, JF ;

Simpson, JW ;

Srinivasan, M ;

Tartaro, KR ;

Tomasz, A ;

Vogt, KA ;

Volkmer, GA .

NATURE, 2005, 437 (7057) :376-380

[8] Encoded self-assembling chemical libraries [J].

Melkko, S ;

Scheuermann, J ;

Dumelin, CE ;

Neri, D .

NATURE BIOTECHNOLOGY, 2004, 22 (05) :568-574

[9] On the magnitude of the chelate effect for the recognition of proteins by pharmacophores scaffolded by self-assembling oligonucleotides [J].

Melkko, S ;

Dumelin, CE ;

Scheuermann, J ;

Neri, D .

CHEMISTRY & BIOLOGY, 2006, 13 (02) :225-231

[10] Encoded self-assembling chemical libraries [J].

Melkko, S ;

Sobek, J ;

Guarda, G ;

Scheuermann, J ;

Dumelin, CE ;

Neri, D .

CHIMIA, 2005, 59 (11) :798-802

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