Cyclic peptides containing tryptophan and arginine as Src kinase inhibitors

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

doi:10.1016/j.bmcl.2013.03.124

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 journal › Article › peer-review

12 Scopus citations

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 language	English (US)
Pages (from-to)	3230-3234
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	23
Issue number	11
DOIs	https://doi.org/10.1016/j.bmcl.2013.03.124
State	Published - Jun 1 2013
Externally published	Yes

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

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10.1016/j.bmcl.2013.03.124

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title = "Cyclic peptides containing tryptophan and arginine as Src kinase inhibitors",

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.",

keywords = "Arginine, Cyclic peptides, Src, Tryptophan, Tyrosine kinase",

author = "{Nasrolahi Shirazi}, Amir and Tiwari, {Rakesh Kumar} and Alex Brown and Dindyal Mandal and Gongqin Sun and Keykavous Parang",

year = "2013",

month = jun,

day = "1",

doi = "10.1016/j.bmcl.2013.03.124",

language = "English (US)",

volume = "23",

pages = "3230--3234",

journal = "Bioorganic and Medicinal Chemistry Letters",

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TY - JOUR

T1 - Cyclic peptides containing tryptophan and arginine as Src kinase inhibitors

AU - Nasrolahi Shirazi, Amir

AU - Tiwari, Rakesh Kumar

AU - Brown, Alex

AU - Mandal, Dindyal

AU - Sun, Gongqin

AU - Parang, Keykavous

PY - 2013/6/1

Y1 - 2013/6/1

N2 - 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.

AB - 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.

KW - Arginine

KW - Cyclic peptides

KW - Src

KW - Tryptophan

KW - Tyrosine kinase

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JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

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ER -

Cyclic peptides containing tryptophan and arginine as Src kinase inhibitors

Abstract

Keywords

ASJC Scopus subject areas

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