Synthesis of de novo designed small-molecule inhibitors of bacterial RNA polymerase

被引：22

作者：

Agarwal, Anil K. ^{[1
]}

Johnson, A. Peter ^{[1
]}

Fishwick, Colin W. G. ^{[1
]}

机构：

[1] Univ Leeds, Sch Chem, Leeds LS2 9JT, W Yorkshire, England

来源：

TETRAHEDRON | 2008年 / 64卷 / 43期

基金：

英国医学研究理事会;

关键词：

D O I：

10.1016/j.tet.2008.08.037

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The de novo molecular design program SPROUT has been used in conjunction with the X-ray crystal structure of RNA polymerase (RNAP) from Thermos aquaticus to produce a novel enzyme inhibitor scaffold. A short and efficient synthesis of molecules corresponding to this scaffold has been developed and in keeping with the design predictions, the resulting inhibitors displayed useful levels of inhibition of Escherichia coli RNAP. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：10049 / 10054

页数：6

共 32 条

[1] New rifabutin analogs:: Synthesis and biological activity against Mycobacterium tuberculosis [J].

Barluenga, Jose ;

Aznar, Fernando ;

Garcia, Ana-Belen ;

Cabal, Maria-Paz ;

Palacios, Juan J. ;

Menendez, Maria-Angela .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2006, 16 (22) :5717-5722

[2] A de Novo designed inhibitor of D-Ala-D-Ala ligase from E-coli [J].

Besong, GE ;

Bostock, JM ;

Stubbings, W ;

Chopra, I ;

Roper, DI ;

Lloyd, AJ ;

Fishwick, CWG ;

Johnson, AP .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2005, 44 (39) :6403-6406

[3] Emerging infectious diseases: Public health issues for the 21st century [J].

Binder, S ;

Levitt, AM ;

Sacks, JJ ;

Hughes, JM .

SCIENCE, 1999, 284 (5418) :1311-1313

[4] TETRACYCLINE STUDIES .5. NEW SYNTHESES OF ANTHRACENES AND ANTHRAQUINONES THROUGH BENZOPHENONE CARBANIONS [J].

BROADHURST, MJ ;

HASSALL, CH ;

THOMAS, GJ .

JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1977, (22) :2502-2512

[5] Structural mechanism for rifampicin inhibition of bacterial RNA polymerase [J].

Campbell, EA ;

Korzheva, N ;

Mustaev, A ;

Murakami, K ;

Nair, S ;

Goldfarb, A ;

Darst, SA .

CELL, 2001, 104 (06) :901-912

[6] Research and development of antibacterial agents [J].

Chopra, I .

CURRENT OPINION IN MICROBIOLOGY, 1998, 1 (05) :495-501

[7] SPROUT - A PROGRAM FOR STRUCTURE GENERATION [J].

GILLET, V ;

JOHNSON, AP ;

MATA, P ;

SIKE, S ;

WILLIAMS, P .

JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN, 1993, 7 (02) :127-153

[8] SPROUT, HIPPO and CAESA: Tools for de novo structure generation and estimation of synthetic accessibility [J].

Gillet, VJ ;

Myatt, G ;

Zsoldos, Z ;

Johnson, AP .

PERSPECTIVES IN DRUG DISCOVERY AND DESIGN, 1995, 3 :34-50

[9] SPROUT - RECENT DEVELOPMENTS IN THE DE-NOVO DESIGN OF MOLECULES [J].

GILLET, VJ ;

NEWELL, W ;

MATA, P ;

MYATT, G ;

SIKE, S ;

ZSOLDOS, Z ;

JOHNSON, AP .

JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES, 1994, 34 (01) :207-217

[10] Combinatorial computational method gives new picomolar ligands for a known enzyme [J].

Grzybowski, BA ;

Ishchenko, AV ;

Kim, CY ;

Topalov, G ;

Chapman, R ;

Christianson, DW ;

Whitesides, GM ;

Shakhnovich, EI .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (03) :1270-1273

← 1 2 3 4 →