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dc.contributor.authorCaracelli, Ignez
dc.contributor.authorVega-Teijido, Mauricio
dc.contributor.authorZukerman-Schpector, Julio
dc.contributor.authorCezari, Maria H. S. [UNIFESP]
dc.contributor.authorLopes, Jose G. S.
dc.contributor.authorJuliano, Luiz [UNIFESP]
dc.contributor.authorSantos, Paulo S.
dc.contributor.authorComasseto, Joao V.
dc.contributor.authorCunha, Rodrigo L. O. R. [UNIFESP]
dc.contributor.authorTiekink, Edward R. T.
dc.identifier.citationJournal of Molecular Structure. Amsterdam: Elsevier B.V., v. 1013, p. 11-18, 2012.
dc.description.abstractThe crystallographically determined structure of biologically active 4,4-dichloro-1,3-diphenyl-4-telluraoct-2-en-1-one, 3, shows the coordination geometry for Te to be distorted psi-pentagonal bipyramidal based on a C2OCl3(lone pair) donor set. Notable is the presence of an intramolecular axial Te center dot center dot center dot O (carbonyl) interaction, a design element included to reduce hydrolysis. Raman and molecular modelling studies indicate the persistence of the Te center dot center dot center dot O(carbonyl) interaction in the solution (CHCl3) and gasphases, respectively. Docking studies of 3' (i.e. original 3 less one chloride) with Cathepsin B reveals a change in the configuration about the vinyl C = C bond. i.e. to E from Z (crystal structure). This isomerism allows the optimisation of interactions in the complex which features a covalent Te-SGCys29 bond. Crucially, the E configuration observed for 3' allows for the formation of a hypervalent Te center dot center dot center dot O interaction as well as an O center dot center dot center dot H-O hydrogen bond with the Gly27 and Glu122 residues, respectively. Additional stabilisation is afforded by a combination of interactions spanning the S1, S2, S1' and S2' sub-sites of Cathepsin B. the greater experimental inhibitory activity of 3 compared with analogues is rationalised by the additional interactions formed between 3' and the His110 and His111 residues in the occluding loop, which serve to hinder the entrance to the active site. (C) 2012 Elsevier B.V. All rights reserved.en
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipMinistry of Higher Education (Malaysia)
dc.publisherElsevier B.V.
dc.relation.ispartofJournal of Molecular Structure
dc.rightsAcesso restrito
dc.subjectCathepsin Ben
dc.subjectX-ray crystal structureen
dc.subjectMolecular modellingen
dc.subjectStructure-activity relationshipsen
dc.titleA tellurium-based cathepsin B inhibitor: Molecular structure, modelling, molecular docking and biological evaluationen
dc.contributor.institutionUniversidade Federal de São Carlos (UFSCar)
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniv Fed Juiz de Fora
dc.contributor.institutionUniversidade Federal do ABC (UFABC)
dc.contributor.institutionUniv Malaya
dc.description.affiliationUniv Fed Sao Carlos, BioMat Dept Fis, BR-13565905 Sao Carlos, SP, Brazil
dc.description.affiliationUniv Estado São Paulo UNESP, Fac Ciencias, Dept Fis, Bauru, SP, Brazil
dc.description.affiliationUniv Fed Sao Carlos, Dept Quim, Lab Cristalog Estereodinam & Modelagem Mol, BR-13565905 Sao Carlos, SP, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biofis, BR-0404420 São Paulo, Brazil
dc.description.affiliationUniv Fed Juiz de Fora, Inst Ciencias Exatas, Dept Quim, Juiz de Fora, MG, Brazil
dc.description.affiliationUniv São Paulo, Inst Quim, São Paulo, Brazil
dc.description.affiliationUniv Fed ABC UFABC, CCNH, Santo Andre, SP, Brazil
dc.description.affiliationUniv Malaya, Dept Chem, Kuala Lumpur 50603, Malaysia
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biofis, BR-0404420 São Paulo, Brazil
dc.description.sponsorshipIDCAPES: 808/2009
dc.description.sponsorshipIDCNPq: 308116/2010-0
dc.description.sponsorshipIDCNPq: 306532/2009-3
dc.description.sponsorshipIDFAPESP: 06/56078-4
dc.description.sponsorshipIDFAPESP: 07/52734-7
dc.description.sponsorshipIDMinistry of Higher Education (Malaysia): UM.C/HIR/MOHE/SC/12
dc.description.sourceWeb of Science
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