Design, synthesis and testing of transition state analogues of alanine racemase as antibacterials

Don K Leung, Peter R Andrews, David Craik, Magdy Iskander, David Winkler

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Transition state analogues have been designed for alanine racemase , an important enzyme target for the development of bacterial cell wall inhibitors. These analogues are based on the transition state structure obtained from MINDO/3 calculations on the reaction pathway of a model alanine racemization . A number of analogues have been synthesized and are shown to have weak anti-bacterial activity, but results from microbiological assays indicate that their antibacterial activity is not due to inhibition of alanine racemase . Subsequent n.m.r .studies have shown that they are unstable in aqueous environments. Formaldehyde has been identified as one of the degradation products, and the likely source of antibacterial activity.
Original languageEnglish
Pages (from-to)297-306
Number of pages10
JournalAustralian Journal of Chemistry
Volume38
Issue number2
DOIs
Publication statusPublished - 1985

Cite this

Leung, Don K ; Andrews, Peter R ; Craik, David ; Iskander, Magdy ; Winkler, David. / Design, synthesis and testing of transition state analogues of alanine racemase as antibacterials. In: Australian Journal of Chemistry. 1985 ; Vol. 38, No. 2. pp. 297-306.
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abstract = "Transition state analogues have been designed for alanine racemase , an important enzyme target for the development of bacterial cell wall inhibitors. These analogues are based on the transition state structure obtained from MINDO/3 calculations on the reaction pathway of a model alanine racemization . A number of analogues have been synthesized and are shown to have weak anti-bacterial activity, but results from microbiological assays indicate that their antibacterial activity is not due to inhibition of alanine racemase . Subsequent n.m.r .studies have shown that they are unstable in aqueous environments. Formaldehyde has been identified as one of the degradation products, and the likely source of antibacterial activity.",
author = "Leung, {Don K} and Andrews, {Peter R} and David Craik and Magdy Iskander and David Winkler",
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Design, synthesis and testing of transition state analogues of alanine racemase as antibacterials. / Leung, Don K; Andrews, Peter R; Craik, David; Iskander, Magdy; Winkler, David.

In: Australian Journal of Chemistry, Vol. 38, No. 2, 1985, p. 297-306.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Andrews, Peter R

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AU - Winkler, David

PY - 1985

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