Construction of a Stapled ?-Helix Peptide Library Displayed on Phage for the Screening of Galectin-3-Binding Peptide Ligands.

ABSTRACT: A stapled ?-helix peptide library was designed and constructed using a chemically modified phage display system for screening stapled-peptide ligands against target proteins. The ?-helix peptide library, with two cysteine residues on the opposite side of the randomized face, was modified with a rigid hydrocarbon staple linker on a phage. The stapled ?-helix peptide phage library was screened against galectin-3 (Gal-3), a cancer-related galactose-binding protein. The obtained stapled peptides showed a high binding affinity (K d = 0.45 ?M) despite being nonsugar ligands. The stapled modification played important roles in stabilizing the ?-helical structure that contributed to the high binding affinity to Gal-3. In addition, the best stapled peptide ligands showed specific binding to Gal-3 among various carbohydrate-binding proteins. Thus, the designed ?-helix peptide phage library with a constrained structure by the staple linker will advance the discovery of peptide ligands with improved specificity and affinity.

SUBMITTER: Anananuchatkul T 

PROVIDER: S-EPMC7097893 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature