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Improving specificity vs bacterial thymidylate synthases through N-dansyl modulation of didansyltyrosine
Donatella Tondi1, Alberto Venturelli, Stefania Ferrari
1Dipartimento di Scienze Farmaceutiche, Università degli Studi di Modena e Reggio Emilia, via Campi 183, 41100 Modena, Italy. tondid@unimore.it
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.
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