Abstract
Protein kinases are implicated in diverse signaling cascades and have been targeted with small molecules that typically bind the conserved ATP-binding active site. These inhibitors are often promiscuous and target multiple protein kinases, which has led to the development of alternate strategies to discover selective ligands. We have recently described a fragment-based selection approach, where a small-molecule warhead can be non-covalently tethered to a phage-displayed library of cyclic peptides. This approach led to the conversion of the promiscuous kinase inhibitor, staurosporine, into a selective bivalent inhibitor.
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Restituyo, E., Camacho-Soto, K., Ghosh, I. (2015). A Fragment-Based Selection Approach for the Discovery of Peptide Macrocycles Targeting Protein Kinases. 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_7
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DOI: https://doi.org/10.1007/978-1-4939-2020-4_7
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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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