Qsar And Molecular Graphics Analysis Of N2-phenylguanines As Inhibitors Of Herpes Simplex Virus Thymidine Kinases

dc.creatorGaudio A.C.
dc.creatorRichards W.Graham
dc.creatorTakahata Y.
dc.date2000
dc.date2015-06-30T19:50:29Z
dc.date2015-11-26T14:47:08Z
dc.date2015-06-30T19:50:29Z
dc.date2015-11-26T14:47:08Z
dc.date.accessioned2018-03-28T21:57:20Z
dc.date.available2018-03-28T21:57:20Z
dc.identifier
dc.identifierJournal Of Molecular Graphics And Modelling. , v. 18, n. 1, p. 33 - 41, 2000.
dc.identifier10933263
dc.identifier10.1016/S1093-3263(00)00032-2
dc.identifierhttp://www.scopus.com/inward/record.url?eid=2-s2.0-0034351146&partnerID=40&md5=694c6bf70f701b97cf9334d95b5143c7
dc.identifierhttp://www.repositorio.unicamp.br/handle/REPOSIP/107217
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/107217
dc.identifier2-s2.0-0034351146
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1253145
dc.descriptionA 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. This single difference in the active sites of both enzymes can explain the source of the steric effect and serves as an indication that our previously proposed binding mode for the PHG derivatives is plausible. However, another observed mutation in the active site region, Ala168 by Ser168, suggests that an alternative binding mode, similar to that of ganciclovir, could be possible. © 2000 by Elsevier Science Inc.
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dc.languageen
dc.publisher
dc.relationJournal of Molecular Graphics and Modelling
dc.rightsfechado
dc.sourceScopus
dc.titleQsar And Molecular Graphics Analysis Of N2-phenylguanines As Inhibitors Of Herpes Simplex Virus Thymidine Kinases
dc.typeArtículos de revistas


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