New simplified inhibitors of EPSP synthase: The importance of ring size for recognition at the shikimate 3-phosphate site

ML Peterson, SD Corey, JL Font, MC Walker…

Index: Peterson, Mark L.; Corey, Susan D.; Font, Jose L.; Walker, Mark C.; Sikorski, James A. Bioorganic and Medicinal Chemistry Letters, 1996 , vol. 6, # 23 p. 2853 - 2858

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Citation Number: 16

Abstract

The simple 4-[(α-hydroxy) phosphonomethyl]-1H-pyrrole-2-carboxylate 4 is a surprisingly good S3P-analog inhibitor of EPSP synthase (competitive with S3P, Ki (app)= 14.5±0.7 μM). The affinity of 4 for free enzyme is nearly comparable to that of S3P (Kd= 7±1.2 μM). Compound 4 thus represents the first successful attempt to replace the highly substituted shikimate ring in S3P with a readily accessible heterocyclic scaffold.