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Synthesis and Screening of One-Bead-One-Compound Cyclic Peptide Libraries

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Peptide Libraries

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1248))

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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Authors and Affiliations

  1. Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH, USA

    Ziqing Qian & Punit Upadhyaya

  2. Department of Chemistry and Biochemistry, The Ohio State University, Bioscience Building Room 578 484 West 12th Avenue, Columbus, OH, 43210, USA

    Dehua Pei

Authors
  1. Ziqing Qian
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  2. Punit Upadhyaya
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  3. Dehua Pei
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Corresponding author

Correspondence to Dehua Pei .

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Editors and Affiliations

  1. Dept of Chemistry, University of Alberta, Edmonton, Alberta, Canada

    Ratmir Derda

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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

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-2019-8

  • Online ISBN: 978-1-4939-2020-4

  • eBook Packages: Springer Protocols

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