title: Improving specificity vs bacterial thymidylate synthases through N-dansyl modulation of didansyltyrosine.
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.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università degli Studi di Modena e Reggio Emilia, via Campi 183, 41100 Modena, Italy. tondid@unimore.it
authors.forename: Donatella
authors.initials: D
authors.lastname: Tondi
authors.forename: Alberto
authors.initials: A
authors.lastname: Venturelli
authors.forename: Stefania
authors.initials: S
authors.lastname: Ferrari
authors.forename: Stefano
authors.initials: S
authors.lastname: Ghelli
authors.forename: M Paola
authors.initials: MP
authors.lastname: Costi
mesh_terms: D001419:Bacteria / Q000201:enzymology*; D003619:Dansyl Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D007780:Lacticaseibacillus casei / Q000201:enzymology; D008958:Models, Molecular; D008968:Molecular Conformation; D011485:Protein Binding; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D003619:Dansyl Compounds; C446819:N,O-didansyl-L-tyrosine; D014443:Tyrosine; D013940:Thymidylate Synthase