当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Design, synthesis, and biochemical evaluation of phosphonate and phosphonamidate analogs of glutathionylspermidine as inhibitors of glutathionylspermidine synthetase/amidase from Escherichia coli.

Design, synthesis, and biochemical evaluation of phosphonate and phosphonamidate analogs of glutathionylspermidine as inhibitors of glutathionylspermidine synthetase/amidase from Escherichia coli.

Abstract：

:Three phosphapeptides designed to mimic two distinct tetrahedral intermediates formed during either the synthesis or hydrolysis of glutathionylspermidine (Gsp) were synthesized and evaluated as inhibitors of the bifunctional enzyme Gsp synthetase/amidase. While the polyamine-containing phosphapeptides were determined to be potent and selective inhibitors, they selectively inhibit the synthetase activity over the amidase domain. A phosphonate-containing tetrahedral mimic is a reversible mixed-type inhibitor of Gsp synthetase with an inhibition constant of 6 microM for the inhibitor binding to the free enzyme (Ki) and 14 microM for the inhibitor binding to the enzyme-substrate complex (Ki'). The corresponding phosphonamidate is a slow-binding inhibitor with a Ki of 24 microM and a Ki* (isomerization inhibition constant) of 0.88 microM. A non-polyamine-containing phosphonamidate exhibits no significant inhibition of the synthetase or amidase activity.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Chen S,Lin CH,Kwon DS,Walsh CT,Coward JK

doi

10.1021/jm970414b

subject

Has Abstract

pub_date

1997-11-07 00:00:00

pages

3842-50

issue

23

eissn

0022-2623

issn

1520-4804

pii

jm970414b

journal_volume

40

pub_type

杂志文章

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