Artículos de revistas
Qsar And Molecular Graphics Analysis Of N2-phenylguanines As Inhibitors Of Herpes Simplex Virus Thymidine Kinases
Registro en:
Journal Of Molecular Graphics And Modelling. , v. 18, n. 1, p. 33 - 41, 2000.
10933263
10.1016/S1093-3263(00)00032-2
2-s2.0-0034351146
Autor
Gaudio A.C.
Richards W.Graham
Takahata Y.
Institución
Resumen
A quantitative structure-activity relationship study of N2-(substituted)-phenylguanines (PHG) as inhibitors of herpes simplex virus thymidine kinase (HSV TK) was performed. The activity of a set of PHG derivatives were analyzed against the thymidine kinase of herpes simplex virus types 1 (HSV1 TK) and 2 (HSV2 TK). Classic and calculated physicochemical parameters were included in the analysis. The results showed that there is an important difference in the activity of the meta substituted PHG derivatives against HSV1 TK and HSV2 TK. The activity of the meta derivatives against HSV2 TK is influenced by a steric effect, which is not observed against HSV1 TK. The superposition of the three-dimensional structures of the active sites of HSV1 TK (crystal structure) and HSV2 TK (homology model) revealed that the amino acid Ile97 is located near the meta position in the HSV1 TK active site, whereas the amino acid Leu97 is located near the meta position in the HSV2 TK active site. 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