Abstract
Peptide-based molecules are known to have therapeutic utility, but the generation of phage-focused libraries to optimize peptide properties and functionality is challenging. Genetic approaches are limited to peptide extension on the peptide termini. Current chemical methods are technically challenging and time-consuming. A new chemical method is developed to extend a maleimide-conjugated peptide with a cysteine-containing random peptide phage display library. As a proof of concept, a 15-mer epidermal growth factor receptor (EGFR)-binding peptide was synthesized with a maleimide group at its C-terminus and then conjugated to the cysteine-containing library. After panning and screening, several extended peptides were discovered and tested to have a higher affinity to EGFR. This strategy can have broad utility to optimize pharmacophores of any modalities (peptides, unnatural peptides, drug conjugates) capable of bearing a maleimide group.
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This work was supported by the Pfizer Postdoctoral Fellowship Program.
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Santoso, B., Murray, B.W. (2015). Maleimide-Based Method for Elaboration of Cysteine-Containing Peptide Phage 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_18
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DOI: https://doi.org/10.1007/978-1-4939-2020-4_18
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Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-2019-8
Online ISBN: 978-1-4939-2020-4
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