Identification and engineering of potent cyclic peptides with selective or promiscuous binding through biochemical profiling and bioinformatic data analysis
Thomas Smith, Bhaskar Bhushan, Daniele Granata, Christian S. Kaas, Birgitte Andersen, Klaas W. Decoene, Qiansheng Ren, Haimo Liu, Xin-Ping Qu, Yang Yang, Pan Jia, Quijia Chen, Martin Münzel, Akane Kawamura
Abstract
cyclic peptide ligands can be rapidly generated against a given target using mRNA display. In this study we harness mRNA display technology and the wealth of next generation sequencing (NGS) data generated to explore both experimental approaches and bioinformatic, statistical data analysis of peptide enrichment in cross-screen selections to rapidly generate high affinity CPs with differing intra-family protein selectivity profiles against fibroblast growth factor receptor (FGF-R) family proteins. Using these methods, CPs with distinct selectivity profiles can be generated which can serve as valuable tool compounds to decipher biological questions.