Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/161250
Full metadata record
DC FieldValueLanguage
dc.contributor.authorLi, Jianguoen_US
dc.contributor.authorKannan, Srinivasaraghavanen_US
dc.contributor.authorAronica, Pietroen_US
dc.contributor.authorBrown, Christopher J.en_US
dc.contributor.authorPartridge, Anthony W.en_US
dc.contributor.authorVerma, Chandra Shekharen_US
dc.date.accessioned2022-08-22T07:10:07Z-
dc.date.available2022-08-22T07:10:07Z-
dc.date.issued2022-
dc.identifier.citationLi, J., Kannan, S., Aronica, P., Brown, C. J., Partridge, A. W. & Verma, C. S. (2022). Molecular descriptors suggest stapling as a strategy for optimizing membrane permeability of cyclic peptides. Journal of Chemical Physics, 156(6), 065101-. https://dx.doi.org/10.1063/5.0078025en_US
dc.identifier.issn0021-9606en_US
dc.identifier.urihttps://hdl.handle.net/10356/161250-
dc.description.abstractCyclic peptides represent a promising class of drug candidates. A significant obstacle limiting their development as therapeutics is the lack of an ability to predict their membrane permeability. We use molecular dynamics simulations to assess the ability of a set of widely used parameters in describing the membrane permeability of a set of model cyclic peptides; the parameters include polar surface area (PSA), the number of hydrogen bonds, and transfer free energy between an aqueous phase and a membrane mimicking phase. These parameters were found to generally correlate with the membrane permeability of the set of cyclic peptides. We propose two new descriptors, the charge reweighted PSA and the non-polar surface area to PSA ratio; both show enhanced correlation with membrane permeability. This inspired us to explore crosslinking of the peptide to reduce the accessible surface area of the backbone polar atoms, and we find that this can indeed result in reductions in the accessible PSA. This gives reason to speculate that crosslinking may result in increased permeability, thus suggesting a new scaffold for the development of cyclic peptides as potential therapeutics.en_US
dc.description.sponsorshipAgency for Science, Technology and Research (A*STAR)en_US
dc.language.isoenen_US
dc.relationH17/01/a0/010en_US
dc.relationIAF111213Cen_US
dc.relationSC16/20-302400en_US
dc.relation.ispartofJournal of Chemical Physicsen_US
dc.rights© 2022 Author(s). All rights reserved. This paper was published by AIP Publishing in Journal of Chemical Physics and is made available with permission of Author(s).en_US
dc.subjectScience::Biological sciencesen_US
dc.titleMolecular descriptors suggest stapling as a strategy for optimizing membrane permeability of cyclic peptidesen_US
dc.typeJournal Articleen
dc.contributor.schoolSchool of Biological Sciencesen_US
dc.contributor.organizationBioinformatics Institute, A*STARen_US
dc.contributor.organizationNational University of Singaporeen_US
dc.identifier.doi10.1063/5.0078025-
dc.description.versionPublished versionen_US
dc.identifier.pmid35168356-
dc.identifier.scopus2-s2.0-85124660214-
dc.identifier.issue6en_US
dc.identifier.volume156en_US
dc.identifier.spage065101en_US
dc.subject.keywordsCell Membrane Permeabilityen_US
dc.subject.keywordsHydrogen Bondingen_US
dc.description.acknowledgementThis work was supported by collaborative grants from MSD and A*STAR (Grant Nos. H17/01/a0/010, IAF111213C, and SC16/20-302400).en_US
item.fulltextWith Fulltext-
item.grantfulltextopen-
Appears in Collections:SBS Journal Articles
Files in This Item:
File Description SizeFormat 
5.0078025.pdf5.58 MBAdobe PDFThumbnail
View/Open

Web of ScienceTM
Citations 50

1
Updated on Oct 27, 2023

Page view(s)

94
Updated on Jul 13, 2024

Download(s)

33
Updated on Jul 13, 2024

Google ScholarTM

Check

Altmetric


Plumx

Items in DR-NTU are protected by copyright, with all rights reserved, unless otherwise indicated.