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Bioprospecting Open Reading Frames for Peptide Effectors

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Therapeutic Peptides

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1088))

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Abstract

Recent successes in the development of small-molecule antagonists of protein–protein interactions designed based on co-crystal structures of peptides bound to their biological targets confirm that short peptides derived from interacting proteins can be high-value ligands for pharmacologic validation of targets and for identification of druggable sites. Evolved sequence space is likely to be enriched for interacting peptides, but identifying minimal peptide effectors within genomic sequence can be labor intensive. Here we describe the use of incremental truncation to diversify genetic material on the scale of open reading frames into comprehensive libraries of constituent peptides. The approach is capable of generating peptides derived from both continuous and discontinuous sequence elements, and is compatible with the expression of free linear or backbone cyclic peptides, with peptides tethered to amino- or carboxyl-terminal fusion partners or with the expression of peptides displayed within protein scaffolds (peptide aptamers). Incremental truncation affords a valuable source of molecular diversity to interrogate the druggable genome or evaluate the therapeutic potential of candidate genes.

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Acknowledgements

The authors wish to thank Eileen Burke, Shirish Damle, and Alex Smith for material contributions and helpful discussions. This work was supported by National Institutes of Health grant R01-AI053800 (awarded to CPS).

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Authors and Affiliations

  1. Department of Biochemistry & Molecular Biology, Thomas Jefferson University, Philadelphia, PA, USA

    Ling Xiong & Charles Scott

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  1. Ling Xiong
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  2. Charles Scott
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Editors and Affiliations

  1. Dyax Corporation Discovery Research, Cambridge, Massachusetts, USA

    Andrew E. Nixon

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© 2014 Springer Science+Business Media, LLC

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Xiong, L., Scott, C. (2014). Bioprospecting Open Reading Frames for Peptide Effectors. In: Nixon, A. (eds) Therapeutic Peptides. Methods in Molecular Biology, vol 1088. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-673-3_6

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  • DOI: https://doi.org/10.1007/978-1-62703-673-3_6

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-672-6

  • Online ISBN: 978-1-62703-673-3

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