Design, synthesis and activity of bisubstrate, transition-state analogues and competitive inhibitors of aspartate transcarbamylase

C Grison, P Coutrot, C Comoy, L Balas, S Joliez…

Index: Grison, Claude; Coutrot, Philippe; Comoy, Corinne; Balas, Laurence; Joliez, Stephane; Lavecchia, Guido; Oliger, Patrick; Penverne, Bernadette; Serre, Valerie; Herve, Guy European Journal of Medicinal Chemistry, 2004 , vol. 39, # 4 p. 333 - 344

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Citation Number: 16

Abstract

Aspartate transcarbamylase initiates the de novo biosynthetic pathway for the production of the pyrimidine nucleotides, precursors of nucleic acids. This pathway is particularly active in rapidly growing cells and tissues. Thus, this enzyme has been tested as a potential target for antiproliferative drugs. In the present work, on the basis of its structural and mechanistic properties, a series of substrate analogues, including potential suicide-pseudosubstrates ...