Young-Hee Shin and Hyunjun Yang
Chem. Commun., 2022,58, 945-948
DOI:
10.1039/D1CC05758H,
Communication
Systematic incorporation of ring-constrained β- and γ-amino acid residues into α-helix mimetics engenders stable helical secondary structures. In this paper, functional α/β/γ-helical peptidomimetics were explored for mimicry of BH3 helical domains, Bim as a pioneering study. The Bim-based α/β/γ-peptides in an αγααβα-hexad repeat with five helical turns inhibited the interaction between Bak and Bcl-xL with excellent resistance towards proteolytic digestion. Further optimization of the α/β/γ-backbone strategy will considerably expand the utility of functional α/β/γ-peptidomimetics, in particular due to its prominent stability against proteolysis.