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.
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Acknowledgements
The work in this laboratory is supported by the National Institutes of Health (GM062820 and CA0132855).
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Qian, Z., Upadhyaya, P., Pei, D. (2015). Synthesis and Screening of One-Bead-One-Compound Cyclic Peptide Libraries. In: Derda, R. (eds) Peptide Libraries. Methods in Molecular Biology, vol 1248. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2020-4_3
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DOI: https://doi.org/10.1007/978-1-4939-2020-4_3
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Online ISBN: 978-1-4939-2020-4
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