title: Synthesis and screening of one-bead-one-compound cyclic peptide libraries.
abstract: Cyclic peptides have been a rich source of biologically active molecules. Herein we present a method for the combinatorial synthesis and screening of large one-bead-one-compound (OBOC) libraries of cyclic peptides against biological targets such as proteins. Up to ten million different cyclic peptides are rapidly synthesized on TentaGel microbeads by the split-and-pool synthesis method and subjected to a multistage screening protocol which includes magnetic sorting, on-bead enzyme-linked and fluorescence-based assays, and in-solution binding analysis of cyclic peptides selectively released from single beads by fluorescence anisotropy. Finally, the most active hit(s) is identified by the partial Edman degradation-mass spectrometry (PED-MS) method. This method allows a single researcher to synthesize and screen up to ten million cyclic peptides and identify the most active ligand(s) in ~1 month, without the time-consuming and expensive hit resynthesis or the use of any special equipment.
authors.affiliation: Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH, USA.
authors.forename: Ziqing
authors.initials: Z
authors.lastname: Qian
authors.forename: Punit
authors.initials: P
authors.lastname: Upadhyaya
authors.forename: Dehua
authors.initials: D
authors.lastname: Pei
mesh_terms: D019151:Peptide Library; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: D019151:Peptide Library; D010456:Peptides, Cyclic