An Update on Protein Kinases as Therapeutic Targets—Part II: Peptides as Allosteric Protein Kinase C Modulators Targeting Protein–Protein Interactions

Mulate Zerihun, Samuel J.S. Rubin, Shmuel Silnitsky, Nir Qvit

Research output: Contribution to journalReview articlepeer-review

1 Scopus citations

Abstract

Human protein kinases are highly-sought-after drug targets, historically harnessed for treating cancer, cardiovascular disease, and an increasing number of autoimmune and inflammatory conditions. Most current treatments involve small molecule protein kinase inhibitors that interact orthosterically with the protein kinase ATP-binding pocket. As a result, these compounds are often poorly selective and highly toxic. Part I of this series reviews the role of PKC isoforms in various human diseases, featuring cancer and cardiovascular disease, as well as translational examples of PKC modulation applied to human health and disease. In the present Part II, we discuss alternative allosteric binding mechanisms for targeting PKC, as well as novel drug platforms, such as modified peptides. A major goal is to design protein kinase modulators with enhanced selectivity and improved pharmacological properties. To this end, we use molecular docking analysis to predict the mechanisms of action for inhibitor–kinase interactions that can facilitate the development of next-generation PKC modulators.

Original languageEnglish
Article number17504
JournalInternational Journal of Molecular Sciences
Volume24
Issue number24
DOIs
StatePublished - 15 Dec 2023

Bibliographical note

Publisher Copyright:
© 2023 by the authors.

Keywords

  • allosteric
  • kinases
  • modified peptides
  • peptides
  • peptidomimetics
  • protein kinase C

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