Combinatorial peptide library screening for discovery of diverse alpha-glucosidase inhibitors using molecular dynamics simulations and binary QSAR models

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dc.contributor.authorMollica, Adriano
dc.contributor.authorZengin, Gökhan
dc.contributor.authorDurdağı, Serdar
dc.contributor.authorSalmas, Ramin Ekhteiari
dc.contributor.authorMacedonio, Giorgia
dc.contributor.authorStefanucci, Azzurra
dc.contributor.authorDimmito, Marilisa Pia
dc.contributor.authorNovellino, Ettore
dc.date.accessioned2020-03-26T20:13:00Z
dc.date.available2020-03-26T20:13:00Z
dc.date.issued2019
dc.departmentSelçuk Üniversitesi, Fen Fakültesi, Biyoloji Bölümüen_US
dc.description.abstractHuman alpha-glucosidase is an enzyme involved in the catalytic cleavage of the glucoside bond and involved in numerous functionalities of the organism, as well as in the insurgence of diabetes mellitus 2 and obesity. Thus, developing chemicals that inhibit this enzyme is a promising approach for the treatment of several pathologies. Small peptides such as di- and tri-peptides may be in natural organism as well as in the GI tract in high concentration, coming from the digestive process of meat, wheat and milk proteins. In this work, we reported the first tentative hierarchical structure-based virtual screening of peptides for human alpha-glucosidase. The goal of this work is to discover novel and diverse lead compounds that my act as inhibitors of alpha-glucosidase such as small peptides by performing a computer aided virtual screening and to find novel scaffolds for further development. Thus, in order to select novel candidates with original structure we performed molecular dynamics (MD) simulations among the 12 top-ranked peptides taking as comparison the MD simulations performed on crystallographic inhibitor acarbose. The compounds with the lower RMSD variability during the MD, were reserved for in vitro biological assay. The selected 4 promising structures were prepared on solid phase peptide synthesis and used for the inhibitory assay, among them compound 2 showed good inhibitory activity, which validated our method as an original strategy to discover novel peptide inhibitors. Moreover, pharmacokinetic profile predictions of these 4 peptides were also carried out with binary QSAR models using MetaCore/MetaDrug applications.en_US
dc.identifier.citationMollica, A., Zengin, G., Durdağı, S., Salmas, R. E., Macedonio, G., Stefanucci, A., Dimmito, M. P., Novellino, E. (2019). Combinatorial Peptide Library Screening for Discovery of Diverse Α-Glucosidase Inhibitors Using Molecular Dynamics Simulations and Binary QSAR Models. Journal of Biomolecular Structure and Dynamics, 37(3), 726-740.
dc.identifier.doi10.1080/07391102.2018.1439403en_US
dc.identifier.endpage740en_US
dc.identifier.issn0739-1102en_US
dc.identifier.issn1538-0254en_US
dc.identifier.issue3en_US
dc.identifier.pmid29421954en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage726en_US
dc.identifier.urihttps://dx.doi.org/10.1080/07391102.2018.1439403
dc.identifier.urihttps://hdl.handle.net/20.500.12395/37597
dc.identifier.volume37en_US
dc.identifier.wosWOS:000458903400013en_US
dc.identifier.wosqualityN/Aen_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.institutionauthorZengin, Gökhan
dc.language.isoenen_US
dc.publisherTAYLOR & FRANCIS INCen_US
dc.relation.ispartofJOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICSen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.selcuk20240510_oaigen_US
dc.subjectAlpha-glucosidaseen_US
dc.subjectInhibitorsen_US
dc.subjectVirtual screeningen_US
dc.subjectDrug designen_US
dc.subjectPeptidesen_US
dc.subjectBinary QSAR modelsen_US
dc.subjectMD simulationsen_US
dc.subjectMetaCore/MetaDrugen_US
dc.titleCombinatorial peptide library screening for discovery of diverse alpha-glucosidase inhibitors using molecular dynamics simulations and binary QSAR modelsen_US
dc.typeArticleen_US

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