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

被引：19

作者：

Tondi, D

Venturelli, A

Ferrari, S

Ghelli, S

Costi, MP

机构：

[1] Univ Modena & Reggio Emilia, Dipartimento Sci Farmaceut, I-41100 Modena, Italy

[2] SPINLAB Srl, Rubiera, RE, Italy

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2005年 / 48卷 / 04期

关键词：

D O I：

10.1021/jm0491445

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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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页码：913 / 916

页数：4

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