A peptide backbone stapling strategy enabled by the multicomponent incorporation of amide n-substituents

dc.creatorRicardo, Manuel G.
dc.creatorMarrrero, Javiel F.
dc.creatorValdés, Oscar
dc.creatorRivera, Daniel G.
dc.creatorWessjohann, Ludger A.
dc.date2023-01-16T19:21:34Z
dc.date2023-01-16T19:21:34Z
dc.date2019
dc.date.accessioned2024-05-02T20:30:22Z
dc.date.available2024-05-02T20:30:22Z
dc.identifierhttp://repositorio.ucm.cl/handle/ucm/4371
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/9274619
dc.descriptionThe multicomponent backbone N-modification of peptides on solid-phase is presented as a powerful and general method to enable peptide stapling at the backbone instead of the side chains. This work shows that a variety of functionalized N-substituents suitable for backbone stapling can be readily introduced by means of on-resin Ugi multicomponent reactions conducted during solid-phase peptide synthesis. Diverse macrocyclization chemistries were implemented with such backbone N-substituents, including the ring-closing metathesis, lactamization, and thiol alkylation. The backbone N-modification method was also applied to the synthesis of α-helical peptides by linking N-substituents to the peptide N-terminus, thus featuring hydrogen-bond surrogate structures. Overall, the strategy proves useful for peptide backbone macrocyclization approaches that show promise in peptide drug discovery.
dc.languageen
dc.rightsAtribución-NoComercial-SinDerivadas 3.0 Chile
dc.rightshttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/
dc.sourceChemistry - A European Journal, 25(3), 769-774
dc.subjectMacrocycles
dc.subjectMulticomponent reactions
dc.subjectPeptide cyclization
dc.subjectStapled peptides
dc.subjectα-helix
dc.titleA peptide backbone stapling strategy enabled by the multicomponent incorporation of amide n-substituents
dc.typeArticle


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