Structure-based design of an aromatic helical foldamer-protein interface.

ABSTRACT: The starting point of this study is the solid state structure of a complex between human carbonic anhydrase II (HCAII) and a helically folded tetradecaamide aromatic foldamer with a nanomolar HCAII ligand appended at the N terminus of the helix. In this complex, the foldamer is achiral but its handedness is biased by diastereoselective interaction with the protein. Computational analysis of the HCAII surface and inspection of the initial solid state structure led to the suggestion of main chain and side chain modifications of the foldamer helix that would result in an extension of the foldamer protein interface as well as in absolute helix handedness control. Molecular dynamics simulations validated several of these suggested modifications as potentially resulting in favorable foldamer-pro

SUBMITTER: Wang L 

PROVIDER: S-EPMC12154549 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature