Cyclic peptides containing tryptophan and arginine as Src kinase inhibitors

Amir Nasrolahi Shirazi, Rakesh Kumar Tiwari, Alex Brown, Dindyal Mandal, Gongqin Sun, Keykavous Parang

Research output: Contribution to journalArticle

Abstract

A number of cyclic and linear peptides containing various combinations of amino acids were evaluated for their Src kinase inhibitory potency. Among all the peptides, cyclic decapeptide C[RW]5 containing alternative arginine (R) and tryptophan (W) residues was found to be the most potent Src kinase inhibitor. C[RW]5 showed higher inhibitory activity (IC 50 = 2.8 μM) than C[KW]5, L(KW)5, C[RW] 4, and C[RW]3 with IC50 values of 46.9, 69.1, 21.5, and 25.0 μM, respectively, as determined in a fluorescence intensity-based assay. Thus, the cyclic nature, the presence of arginine, ring size, and the number of amino acids in the structure of the peptide were found to be critical in Src kinase inhibitory potency. The IC50 value of C[RW]5 was found to be 0.8 μM in a radioactive assay using [γ-32P]-ATP and polyE4Y as the substrate. C[RW] 5 was a noncompetitive Src kinase inhibitor, showing approximately fourfold more selectivity towards Src than Abl.

Original languageEnglish (US)
Pages (from-to)3230-3234
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume23
Issue number11
DOIs
StatePublished - Jun 1 2013
Externally publishedYes

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Keywords

  • Arginine
  • Cyclic peptides
  • Src
  • Tryptophan
  • Tyrosine kinase

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

Cite this

Nasrolahi Shirazi, A., Tiwari, R. K., Brown, A., Mandal, D., Sun, G., & Parang, K. (2013). Cyclic peptides containing tryptophan and arginine as Src kinase inhibitors. Bioorganic and Medicinal Chemistry Letters, 23(11), 3230-3234. https://doi.org/10.1016/j.bmcl.2013.03.124