Towards the development of novel antibiotics: Synthesis and evaluation of a mechanism-based inhibitor of Kdo8P synthase

Authors
Du, SC Faiger, H Belakhov, V Baasov, T
Citation
Sc. Du et al., Towards the development of novel antibiotics: Synthesis and evaluation of a mechanism-based inhibitor of Kdo8P synthase, BIO MED CH, 7(12), 1999, pp. 2671-2682
Citations number
40
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY
ISSN journal
09680896 → ACNP
Volume
7
Issue
12
Year of publication
1999
Pages
2671 - 2682
Database
ISI
SICI code
0968-0896(199912)7:12<2671:TTDONA>2.0.ZU;2-V
Abstract
The design and two synthetic pathways to aminophosphonate 4 which mimics th e ionic and steric properties of putative oxocarbenium intermediate 3 in th e Kdo8P synthase-catalyzed reaction are reported. It was found that 4 is a slow-binding, most potent inhibitor of the enzyme yet tested, with a K-i va lue of 0.4 mu M. (C) 1999 Elsevier Science Ltd. All rights reserved.