TY - JOUR A1 - Gruß, Hendrik A1 - Feiner, Rebecca C. A1 - Mseya, Ridhiwan A1 - Schröder, David C. A1 - Jewgiński, Michał A1 - Müller, Kristian M. A1 - Latajka, Rafał A1 - Marion, Antoine A1 - Sewald, Norbert T1 - Peptide stapling by late-stage Suzuki–Miyaura cross-coupling JF - Beilstein Journal of Organic Chemistry PY - 2022/// VL - 18 SP - 1 EP - 12 SN - 1860-5397 DO - 10.3762/bjoc.18.1 PB - Beilstein-Institut JA - Beilstein J. Org. Chem. UR - https://doi.org/10.3762/bjoc.18.1 KW - accelerated molecular dynamics KW - halotryptophan KW - intrinsically disordered peptides KW - late-stage diversification KW - macrocyclisation KW - molecular dynamics KW - stapled peptides KW - Suzuki–Miyaura cross-coupling N2 - 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. ER -