Molecular design of stapled pentapeptides as building blocks of self-assembled coiled coil-like fibers.

ABSTRACT: Peptide self-assembly inspired by natural superhelical coiled coils has been actively pursued but remains challenging due to limited helicity of short peptides. Side chain stapling can strengthen short helices but is unexplored in design of self-assembled helical nanofibers as it is unknown how staples could be adapted to coiled coil architecture. Here, we demonstrate the feasibility of this design for pentapeptides using a computational method capable of predicting helicity and fiber-forming tendency of stapled peptides containing noncoded amino acids. Experiments showed that the best candidates, which carried an aromatically substituted staple and phenylalanine analogs, displayed exceptional helicity and assembled into nanofibers via specific head-to-tail hydrogen bonding and packing bet

SUBMITTER: Jiang Y 

PROVIDER: S-EPMC10662664 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature