A de Novo designed inhibitor of D-Ala-D-Ala ligase from E-coli

被引：34

作者：

Besong, GE

Bostock, JM

Stubbings, W

Chopra, I

Roper, DI

Lloyd, AJ

Fishwick, CWG ^{[1
]}

Johnson, AP

机构：

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

[2] Univ Leeds, Dept Biochem & Mol Biol, Leeds LS2 9JT, W Yorkshire, England

[3] Univ Warwick, Dept Biol Sci, Coventry CV4 7AL, W Midlands, England

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2005年 / 44卷 / 39期

基金：

英国医学研究理事会;

关键词：

inhibitors; ligases; medicinal chemistry; molecular modeling; molecular recognition;

D O I：

10.1002/anie.200501662

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

(Figure Presented) Blueprints for an inhibitor: The de novo molecular design program SPROUT was used in conjunction with the X-ray crystal structures of the bacterial enzymes DdlB and VanA to produce a novel enzyme-selective inhibitor template. Following short and efficient synthesis and in keeping with the design predictions, the resulting inhibitor showed useful levels of enzyme-selective inhibition. © 2005 Wiley-VCH Verlag GmbH & Co. KGaA.

引用

收藏

页码：6403 / 6406

页数：4

相关论文

共 25 条

[1] The role of virtual screening in computer aided structure-based drug design [J].

Branson, KM ;

Smith, BJ .

AUSTRALIAN JOURNAL OF CHEMISTRY, 2004, 57 (11) :1029-1037

[2]

CHENG Y, 1973, BIOCHEM PHARMACOL, V22, P3099

[3] Biochemical characterization of an inhibitor of Escherichia coli UDP-N-acetylmuramyl-L-alanine ligase [J].

Ehmann, DE ;

Demeritt, JE ;

Hull, KG ;

Fisher, SL .

BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, 2004, 1698 (02) :167-174

[4] Identification of novel inhibitors of Pseudomonas aeruginosa MurC enzyme derived from phage-displayed peptide libraries [J].

El Zoeiby, A ;

Sanschagrin, F ;

Darveau, A ;

Brisson, JR ;

Levesque, RC .

JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 2003, 51 (03) :531-543

[5] VANCOMYCIN RESISTANCE - STRUCTURE OF D-ALANINE-D-ALANINE LIGASE AT 2.3-ANGSTROM RESOLUTION [J].

FAN, C ;

MOEWS, PC ;

WALSH, CT ;

KNOX, JR .

SCIENCE, 1994, 266 (5184) :439-443

[6] Inhibitors of the bacterial cell wall biosynthesis enzyme MurD [J].

Gegnas, LD ;

Waddell, ST ;

Chabin, RM ;

Reddy, S ;

Wong, KK .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1998, 8 (13) :1643-1648

[7] 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

[8]

Green David W, 2002, Expert Opin Ther Targets, V6, P1, DOI 10.1517/14728222.6.1.1

[9] 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

[10] Design, synthesis, and biological evaluation of potent and selective amidino bicyclic factor Xa inhibitors [J].

Han, Q ;

Dominguez, C ;

Stouten, PFW ;

Park, JM ;

Duffy, DE ;

Galemmo, RA ;

Rossi, KA ;

Alexander, RS ;

Smallwood, AM ;

Wong, PC ;

Wright, MM ;

Luettgen, JM ;

Knabb, RM ;

Wexler, RR .

JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (23) :4398-4415