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Peptide stapling by late-stage Suzuki-Miyaura cross-coupling.

ABSTRACT: The development of peptide stapling techniques to stabilise α-helical secondary structure motifs of peptides led to the design of modulators of protein-protein interactions, which had been considered undruggable for a long time. We disclose a novel approach towards peptide stapling utilising macrocyclisation by late-stage Suzuki-Miyaura cross-coupling of bromotryptophan-containing peptides of the catenin-binding domain of axin. Optimisation of the linker length in order to find a compromise between both sufficient linker rigidity and flexibility resulted in a peptide with an increased α-helicity and enhanced binding affinity to its native binding partner β-catenin. An increased proteolytic stability against proteinase K has been demonstrated.

SUBMITTER: Gruß H

PROVIDER: S-EPMC8744458 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Peptide stapling by late-stage Suzuki-Miyaura cross-coupling.

Gruß Hendrik H Feiner Rebecca C RC Mseya Ridhiwan R Schröder David C DC Jewgiński Michał M Müller Kristian M KM Latajka Rafał R Marion Antoine A Sewald Norbert N

Beilstein journal of organic chemistry 20220103

The development of peptide stapling techniques to stabilise α-helical secondary structure motifs of peptides led to the design of modulators of protein-protein interactions, which had been considered undruggable for a long time. We disclose a novel approach towards peptide stapling utilising macrocyclisation by late-stage Suzuki-Miyaura cross-coupling of bromotryptophan-containing peptides of the catenin-binding domain of axin. Optimisation of the linker length in order to find a compromise betw ...[more]

PMID: 35047078

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