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Novel Peptide-Based Inhibitors of Protein Kinases

Abstract

Protein kinases are a class of enzymes that modulate the function and activity of other proteins through phosphorylation. Protein kinases regulate many aspects of cellular metabolism including signal transduction, transcription, translation, cell-cycle progression, and biosynthesis. Owing to their profound influence over such critical cellular processes, mutations or aberrant expression of protein kinases can have major implications on cell health and viability. Indeed, dysfunctional protein kinase activity has been linked to such pathological conditions as neurodegeneration, inflammation, autoimmunity, and cancer. Despite their therapeutic importance, our ability to target discrete protein kinases using small-molecule-based inhibitors has been hindered due to high degrees of structural similarity among protein kinase active sites. Recently, peptides have emerged as powerful, yet selective, modulators of protein kinase activity by virtue of their ability to mimic highly specific substrate-interaction domains of protein kinases. This chapter provides an overview of the development and application of novel peptide-based protein kinase inhibitors. The goal here is to highlight how the various binding modes of peptide-based kinase inhibitors and efforts to enhance their binding affinities have contributed to the understanding of the complex nature of protein kinase–substrate interactions. Furthermore, the therapeutic relevance of peptide-based kinase inhibitors is explored, focusing on the advantages and limitations of such molecules as they are applied in the treatment of kinase-mediated disease.

Keywords

  • Protein kinase
  • Peptide
  • Protein kinase inhibitor
  • Peptide-based therapeutic
  • Protein kinase substrate
  • Peptide-based kinase inhibitor
  • Protein kinase interaction domain
  • Protein-protein interactions

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Holub, J.M. (2020). Novel Peptide-Based Inhibitors of Protein Kinases. In: Shapiro, P. (eds) Next Generation Kinase Inhibitors. Springer, Cham. https://doi.org/10.1007/978-3-030-48283-1_8

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