title: Synthesis and molecular modeling of novel HSV1 uracil-DNA glycosylase inhibitors.
abstract: In a recent paper the first selective inhibitors of HSV1 uracil-DNA glycosylase (UDG) acting in the micromolar range have been reported. A 28.5 kDa catalytic fragment of HSV1 UDG has been crystallized in the presence of uracil, and the structure was recently solved. Starting with the optimized model of binding between 6-(4'-n-octylanilino)uracil (octAU) and UDG some new derivatives have been predicted to be active. In vitro studies with the novel synthetized compounds confirm the plausibility of the model and define the structure features for UDG inhibitors.
authors.affiliation: Dipartimento di Chimica Farmaceutica, Università degli Studi, Pavia, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Pregnolato
authors.forename: D
authors.initials: D
authors.lastname: Ubiali
authors.forename: A
authors.initials: A
authors.lastname: Verri
authors.forename: F
authors.initials: F
authors.lastname: Focher
authors.forename: S
authors.initials: S
authors.lastname: Spadari
authors.forename: H
authors.initials: H
authors.lastname: Sun
authors.forename: C
authors.initials: C
authors.lastname: Zhi
authors.forename: G E
authors.initials: GE
authors.lastname: Wright
mesh_terms: D045647:DNA Glycosylases; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D018259:Herpesvirus 1, Human / Q000201:enzymology*; D008958:Models, Molecular; D009699:N-Glycosyl Hydrolases / Q000037:antagonists & inhibitors*; D013816:Thermodynamics; D051981:Uracil-DNA Glycosidase
chemical_list: D004791:Enzyme Inhibitors; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; D051981:Uracil-DNA Glycosidase