Helical sulfono-γ-AApeptides with predictable functions in protein recognition

Abstract

This review mainly summarizes the helical folding conformations of sulfono-γ-AApeptides and their biological applications in protein–protein interactions and assesses their potential for the mimicry of other α-helices for protein recognition.

Helical sulfonyl-γ-AApeptides for the inhibition of HIV-1 fusion and HIF-1α signaling

“…Secondly, although the left-handedness is opposite to the natural right-handedness observed in the α-helical domain of proteins, the similar helical pitch to α-helix (5.1 Å) and the robust folding framework of exactly four side chains per turn, which enables a straightforward design with predicted structure and function for protein binding. 12,25…”

Unnatural helical peptidic foldamers as protein segment mimics

“…1) were designed by our group and were first reported in 2015. 14,[50][51][52] Derived from g-chiral PNA (peptide nucleic acid), sulfono-g-AA building units are comparable to a conventional dipeptide residue in length and contain the same number of side chains as the conventional dipeptide. In the sulfono-g-AA amino acid unit, one side chain is derived from the chiral group of canonical amino acid, whereas another side chain is introduced by sulfonyl chlorides, providing an enormous chemical diversity.…”

An HR2-Mimicking Sulfonyl-γ-AApeptide Is a Potent Pan-coronavirus Fusion Inhibitor with Strong Blood–Brain Barrier Permeability, Long Half-Life, and Promising Oral Bioavailability

“…Non-natural sequence-specific peptidomimetics have become a promising alternative strategy to modulate protein–protein interactions (PPIs) − to alleviate issues associated with the intrinsic drawbacks of peptides. In addition to retaining the advantages of natural peptides, foldameric peptidomimetics also exhibit unique structures and functions and are highly resistant to enzymatic hydrolysis. , We have developed a new class of peptidomimetics, γ-AApeptides − (oligomers of N -acyl- N -aminoethyl amino acids), based on the γ-chiral peptide nucleic acid (PNA) backbone. They show extraordinary resistance to proteolytic degradation and amenability to chemical diversification, making them suitable candidates for a variety of biological applications. ,− As a subclass of γ-AApeptides, sulfonyl-γ-AApeptides (Figure A) not only possess the merits noted above but can also adopt well-defined helical structures − (Figure B,C).…”