Cyclic peptides containing tryptophan and arginine as Src kinase inhibitors

Authors

Amir Nasrolahi Shirazi
Rakesh Kumar Tiwari
Alex Brown
Dindyal Mandal
Gongqin Sun, University of Rhode IslandFollow
Keykavous Parang, University of Rhode IslandFollow

Document Type

Article

Date of Original Version

2013

Department

Cell & Molecular Biology

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 (IC₅₀ = 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.

Publication Title, e.g., Journal

Bioorganic & Medicinal Chemistry Letters

Volume

23

Issue

11

Citation/Publisher Attribution

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 & Medicinal Chemistry Letters, 23(11), 3230-3234. https://doi.org/10.1016/j.bmcl.2013.03.124

Available at: https://doi.org/10.1016/j.bmcl.2013.03.124