Construction of a Stapled α-Helix Peptide Library Displayed on Phage for the Screening of Galectin-3-Binding Peptide Ligands
Construction of a Stapled α-Helix Peptide Library Displayed on Phage for the Screening of Galectin-3-Binding Peptide Ligands
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DOI：
10.1021/acsomega.9b03461
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发表时间：
2020-03-24
期刊：
影响因子：
4.1
通讯作者：
Mihara, Hisakazu
中科院分区：
文献类型：
--
作者：
Anananuchatkul, Teerapat;Chang, Iou Ven;Mihara, Hisakazu
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A stapled alpha-helix peptide library was designed and constructed using a chemically modified phage display system for screening stapled-peptide ligands against target proteins. The alpha-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 alpha-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 mu M) despite being nonsugar ligands. The stapled modification played important roles in stabilizing the alpha-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 alpha-helix peptide phage library with a constrained structure by the staple linker will advance the discovery of peptide ligands with improved specificity and affinity.