Chemical protein synthesis-assisted high-throughput screening strategies for d-peptides in drug discovery

• Published in: Chinese chemical letters Vol. 31; no. 9; pp. 2365 - 2374
• Main Authors: Li, Ying, Cao, Xiuxiu, Tian, Changlin, Zheng, Ji-Shen
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.09.2020; Department of Chemistry, School of Life Sciences, Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei 230027, China%High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei 230031, China%Department of Chemistry, School of Life Sciences, Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei 230027, China; High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei 230031, China
• Subjects: Chemical protein synthesis; d-Peptide drug; Mirror-image one-bead one-compound (OBOC); Mirror-image phage display; Mirror-image proteins; Mirror-image proteins; Chemical protein synthesis; Mirror-image phage display; d-Peptide drug; Mirror-image one-bead one-compound (OBOC); D-Peptide drug
• ISSN: 1001-8417; 1878-5964
• DOI: 10.1016/j.cclet.2020.04.015

Chemical protein synthesis-assisted high-throughput screening strategies (e.g., mirror-image phage display, mirror-image one-bead one-compound approaches) for d-peptide ligands were reviewed. [Display omitted] d-peptides are recognized as a new class of synthetic chemical drugs and they possess many interesting advantages such as high enzymatic stability, improved oral bioavailability, as well as high binding affinity and specificity. Recently, d-peptide drugs have been attracting increasing attention in both academic and industrial researches over recent years. One d-peptide etelcalcetide has even entered the market that targets the calcium (Ca2+)-sensing receptor (CaSR) to fight secondary hyperparathyroidism. Effective discovery and optimization of d-peptide ligands that can bind to various disease-related targets with high specificity and potency is of great importance for the development of d-peptide drugs. This review surveys the recent method development in this area especially the chemical protein synthesis-assisted high-throughput screening strategies for d-peptide ligands and their application in drug discovery.