Document Type
Article
Publication Date
6-1-2013
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-(32)P]-ATP and polyE4Y as the substrate. C[RW]5 was a noncompetitive Src kinase inhibitor, showing approximately fourfold more selectivity towards Src than Abl.
Recommended Citation
Nasrolahi Shirazi, Amir, Rakesh Kumar Tiwari, Alex Brown, Dindyal Mandal, Gongqin Sun, and Keykavous Parang. "Cyclic peptides containing tryptophan and arginine as Src kinase inhibitors." Bioorganic & medicinal chemistry letters 23, no. 11 (2013): 3230-3234.
DOI:10.1016/j.bmcl.2013.03.124
Copyright
Elsevier
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
Comments
NOTICE: this is the author’s version of a work that was accepted for publication in Bioorganic & Medicinal Chemistry Letters. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Bioorganic & Medicinal Chemistry Letters, volume 23, issue 11, 2013. DOI: 10.1016/j.bmcl.2013.03.124
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