Peptide stapling by late-stage Suzuki-Miyaura cross-coupling
BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY, cilt.18, 2022 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 18
- Basım Tarihi: 2022
- Doi Numarası: 10.3762/bjoc.18.1
- Dergi Adı: BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Aquatic Science & Fisheries Abstracts (ASFA), Biotechnology Research Abstracts, Chemical Abstracts Core, Directory of Open Access Journals
- Anahtar Kelimeler: accelerated molecular dynamics, halotryptophan, intrinsically disordered peptides, late-stage diversification, macrocyclisation, molecular dynamics, stapled peptides, Suzuki-Miyaura cross-coupling, ACCELERATED MOLECULAR-DYNAMICS, ALPHA-HELICAL PEPTIDES, ENZYMATIC HALOGENATION, TRYPTOPHAN, ARYLATION, MACROCYCLIZATION, DIVERSIFICATION, MILD, SIMULATIONS, STABILITY
- Orta Doğu Teknik Üniversitesi Adresli: Evet
Özet
The development of peptide stapling techniques to stabilise alpha-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 alpha-helicity and enhanced binding affinity to its native binding partner beta-catenin. An increased proteolytic stability against proteinase K has been demonstrated.