Cyclic peptides containing tryptophan and arginine as Src kinase inhibitors |
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| Authors: | Amir Nasrolahi Shirazi Rakesh Kumar Tiwari Alex Brown Dindyal Mandal Gongqin Sun Keykavous Parang |
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| Institution: | 1. Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI 02881, United States;2. Department of Cell and Molecular Biology, University of Rhode Island, Kingston, RI 02881, United States |
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| 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 CRW]5 containing alternative arginine (R) and tryptophan (W) residues was found to be the most potent Src kinase inhibitor. CRW]5 showed higher inhibitory activity (IC50 = 2.8 μM) than CKW]5, L(KW)5, CRW]4, and CRW]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 CRW]5 was found to be 0.8 μM in a radioactive assay using γ-32P]-ATP and polyE4Y as the substrate. CRW]5 was a noncompetitive Src kinase inhibitor, showing approximately fourfold more selectivity towards Src than Abl. |
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| Keywords: | Arginine Cyclic peptides Src Tryptophan Tyrosine kinase |
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