Abstract |
A stapled α-helix peptide library was designed and constructed using a chemically modified phage display system for screening stapled- peptide ligands against target proteins. The α-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 α-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 μM) despite being nonsugar ligands. The stapled modification played important roles in stabilizing the α-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 α-helix peptide phage library with a constrained structure by the staple linker will advance the discovery of peptide ligands with improved specificity and affinity.
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Authors | Teerapat Anananuchatkul, Iou Ven Chang, Takayuki Miki, Hiroshi Tsutsumi, Hisakazu Mihara |
Journal | ACS omega
(ACS Omega)
Vol. 5
Issue 11
Pg. 5666-5674
(Mar 24 2020)
ISSN: 2470-1343 [Electronic] United States |
PMID | 32226843
(Publication Type: Journal Article)
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Copyright | Copyright © 2020 American Chemical Society. |