[Fluorinated analogues of tryptophan showing substrate and inhibitor activity in the ATP-32ppi exchange reaction catalysed by tryptophanyl tRNA synthetase]

Abstract

L-6-Flurotryptophan and D,L-5-fluorotryptophan stimulate ATP-32PPi exchange reaction catalysed by tryptophanyl tRNA synthetase from beef pancreas. Exchange reactions proceeding in the presence of these analogues of the substrate amino acid show distinct values of maximum rate and similar Km values. D,L-5,7-Difluorotryptophan and D,L-4,5,6,7-tetrafluorotryptophan competetively inhibit the exchange reaction stimulated by L-tryptophan. Introduction of a single fluorine atom into the tryptophan indole ring results in a decrease of the affinity for the enzyme by one order. The affinity of difluorotryptophan is two orders less than that of L-tryptophan. D,L-5,7-Difluorotryptophan has been synthesized by cyclization of acetamide dicarboetoxy butyric aldehyde upon boiling in 8% H2SO4 solution. Optically pure L-6-fluorotryptophan was isolated from the racemic mixture by using oxidase of D-amino acids.