Journal of Medicinal Chemistry 2005-02-24

Improving specificity vs bacterial thymidylate synthases through N-dansyl modulation of didansyltyrosine.

Donatella Tondi, Alberto Venturelli, Stefania Ferrari, Stefano Ghelli, M Paola Costi

Index: J. Med. Chem. 48 , 913-916, (2005)

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Abstract

N,O-Didansyl-L-tyrosine (DDT) represented the starting lead for further development of novel non-substrate-like inhibitors of bacterial thymidylate synthase. The N-dansyl structure modulation led to a submicromolar inhibitor of Lactobacillus casei TS (LcTS), which is highly specific with respect to human TS (hTS). Using molecular dynamics simulation, a binding mode for DDT vs LcTS was predicted, explaining activity and species-specificity along the series.