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

Beilstein Journal of Organic Chemistry

Rafał Latajka¹  Michał Jewgiński¹  Hendrik Gruß²  David C. Schröder²  Norbert Sewald²  Ridhiwan Mseya³  Antoine Marion³  Rebecca C. Feiner⁴  Kristian M. Müller⁴ 

[1] Department of Bioorganic Chemistry, Wrocław University of Science and Technology, Wybrzeze Wyspianskiego 27, 50-370 Wrocław, Poland;Department of Chemistry, Bielefeld University, Universitätsstr. 25, 33615 Bielefeld, Germany;Department of Chemistry, Middle East Technical University, 06800, Ankara, Turkey;Department of Technology, Bielefeld University, Universitätsstr. 25, 33615 Bielefeld, Germany;

关键词: accelerated molecular dynamics;    halotryptophan;    intrinsically disordered peptides;    late-stage diversification;    macrocyclisation;    molecular dynamics;    stapled peptides;    suzuki–miyaura cross-coupling;   

DOI  :  10.3762/bjoc.18.1

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown