Show simple item record

dc.creatorIslam, Md Shafiqul
dc.creatorJunod, Samuel
dc.creatorZhang, Si
dc.creatorBuuh, Zakey Yusuf
dc.creatorGuan, Yifu
dc.creatorZhao, Mi
dc.creatorKaneria, Kishan H.
dc.creatorKafley, Parmila
dc.creatorCohen, Carson
dc.creatorMaloney, Robert
dc.creatorLyu, Zhigang
dc.creatorVoelz, Vincent
dc.creatorYang, Weidong
dc.creatorWang, Rongsheng E.
dc.date.accessioned2023-12-21T18:33:31Z
dc.date.available2023-12-21T18:33:31Z
dc.date.issued2022-01-17
dc.identifier.citationIslam, M.S., Junod, S.L., Zhang, S. et al. Unprotected peptide macrocyclization and stapling via a fluorine-thiol displacement reaction. Nat Commun 13, 350 (2022). https://doi.org/10.1038/s41467-022-27995-5
dc.identifier.issn2041-1723
dc.identifier.urihttp://hdl.handle.net/20.500.12613/9295
dc.description.abstractWe report the discovery of a facile peptide macrocyclization and stapling strategy based on a fluorine thiol displacement reaction (FTDR), which renders a class of peptide analogues with enhanced stability, affinity, cellular uptake, and inhibition of cancer cells. This approach enabled selective modification of the orthogonal fluoroacetamide side chains in unprotected peptides in the presence of intrinsic cysteines. The identified benzenedimethanethiol linker greatly promoted the alpha helicity of a variety of peptide substrates, as corroborated by molecular dynamics simulations. The cellular uptake of benzenedimethanethiol stapled peptides appeared to be universally enhanced compared to the classic ring-closing metathesis (RCM) stapled peptides. Pilot mechanism studies suggested that the uptake of FTDR-stapled peptides may involve multiple endocytosis pathways in a distinct pattern in comparison to peptides stapled by RCM. Consistent with the improved cell permeability, the FTDR-stapled lead Axin and p53 peptide analogues demonstrated enhanced inhibition of cancer cells over the RCM-stapled analogues and the unstapled peptides.
dc.format.extent16 pages
dc.languageEnglish
dc.language.isoeng
dc.relation.ispartofFaculty/ Researcher Works
dc.relation.haspartNature Communications, Vol. 13
dc.relation.isreferencedbyNature Research
dc.rightsAttribution CC BY
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectCancer
dc.subjectChemical modification
dc.subjectChemical tools
dc.subjectPeptides
dc.subjectProteins
dc.titleUnprotected peptide macrocyclization and stapling via a fluorine-thiol displacement reaction
dc.typeText
dc.type.genreJournal article
dc.description.departmentChemistry
dc.description.departmentBiology
dc.relation.doihttp://dx.doi.org/10.1038/s41467-022-27995-5
dc.ada.noteFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
dc.description.schoolcollegeTemple University. College of Science and Technology
dc.creator.orcidJunod|0000-0002-4288-0240
dc.creator.orcidZhang|0000-0002-1164-2020
dc.creator.orcidGuan|0000-0002-0800-7069
dc.creator.orcidZhao|0000-0002-2051-1196
dc.creator.orcidMaloney|0000-0001-8704-816X
dc.creator.orcidLyu|0000-0002-6903-3965
dc.creator.orcidVoelz|0000-0002-1054-2124
dc.creator.orcidYang|0000-0002-2615-189X
dc.temple.creatorIslam, Md Shafiqul
dc.temple.creatorJunod, Samuel L.
dc.temple.creatorZhang, Si
dc.temple.creatorBuuh, Zakey Yusuf
dc.temple.creatorGuan, Yifu
dc.temple.creatorZhao, Mi
dc.temple.creatorKaneria, Kishan H.
dc.temple.creatorKafley, Parmila
dc.temple.creatorCohen, Carson
dc.temple.creatorMaloney, Robert
dc.temple.creatorLyu, Zhigang
dc.temple.creatorVoelz, Vincent A.
dc.temple.creatorYang, Weidong
dc.temple.creatorWang, Rongsheng E.
refterms.dateFOA2023-12-21T18:33:31Z


Files in this item

Thumbnail
Name:
IslamEtAl-JournalArticle-2022- ...
Size:
2.743Mb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record

Attribution CC BY
Except where otherwise noted, this item's license is described as Attribution CC BY