Design and synthesis of aromatic inhibitors of anthranilate synthase.

Payne, Richard J; Bulloch, Esther M M; Abell, Andrew D; Abell, Chris

Payne, Richard J; Bulloch, Esther M M; Abell, Andrew D; Abell, Chris.

Afiliación

Payne RJ; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, UKCB2 1EW.

Org Biomol Chem ; 3(20): 3629-35, 2005 Oct 21.

Article en En | MEDLINE | ID: mdl-16211099

RESUMEN

Anthranilate synthase catalyses the conversion of chorismate to anthranilate, a key step in tryptophan biosynthesis. A series of 3-(1-carboxy-ethoxy) benzoic acids were synthesised as chorismate analogues, with varying functionality at C-4, the position of the departing hydroxyl group in chorismate. Most of the compounds were moderate inhibitors of anthranilate synthase, with inhibition constants between 20-30 microM. The exception was 3-(1-carboxy-ethoxy) benzoic acid, (C-4 = H), for which K(I)= 2.4 microM. These results suggest that a hydrogen bonding interaction with the active site general acid (Glu309) is less important than previously assumed for inhibition of the enzyme by these aromatic chorismate analogues.

Asunto(s)

Antranilato Sintasa/antagonistas & inhibidores; Benzoatos/síntesis química; Benzoatos/farmacología; Inhibidores Enzimáticos/síntesis química; Inhibidores Enzimáticos/farmacología; Antranilato Sintasa/química; Benzoatos/química; Sitios de Unión; Ácido Corísmico/análogos & derivados; Ácido Corísmico/síntesis química; Ácido Corísmico/química; Activación Enzimática/efectos de los fármacos; Inhibidores Enzimáticos/química; Enlace de Hidrógeno; Modelos Moleculares; Estructura Molecular; Serratia marcescens/efectos de los fármacos; Serratia marcescens/enzimología; Estereoisomerismo; Relación Estructura-Actividad

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Benzoatos / Inhibidores Enzimáticos / Antranilato Sintasa Idioma: En Revista: Org Biomol Chem Asunto de la revista: BIOQUIMICA / QUIMICA Año: 2005 Tipo del documento: Article Pais de publicación: Reino Unido

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