Synthesis and structure-activity relationships of linear and conformationally constrained peptide analogues of CIYKYY as Src tyrosine kinase inhibitors

Anil Kumar; Guofeng Ye; Yuehao Wang; Xiaofeng Lin; Gongqin Sun; Keykavous Parang

doi:10.1021/jm060334k

Synthesis and structure-activity relationships of linear and conformationally constrained peptide analogues of CIYKYY as Src tyrosine kinase inhibitors

Anil Kumar, Guofeng Ye, Yuehao Wang, Xiaofeng Lin, Gongqin Sun, Keykavous Parang

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

A series of peptide analogues of Ac-CIYKYY (1) were synthesized by functional group modifications in peptide side chains or by introducing conformational constraints, to improve the inhibitory potency against active Src kinase. Ac-CIYKF(4-NO₂)Y (2, IC₅₀ = 0.53 μM) and conformationally constrained peptide 31 (IC₅₀ = 0.28 μM) exhibited 750- and 1400-fold higher inhibitory activities, respectively, versus that of 1 (IC₅₀ = 400 μM). Compound 2 exhibited a partial competitive inhibition pattern against ATP.

Original language	English (US)
Pages (from-to)	3395-3401
Number of pages	7
Journal	Journal of Medicinal Chemistry
Volume	49
Issue number	11
DOIs	https://doi.org/10.1021/jm060334k
State	Published - Jun 1 2006
Externally published	Yes

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Organic Chemistry

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title = "Synthesis and structure-activity relationships of linear and conformationally constrained peptide analogues of CIYKYY as Src tyrosine kinase inhibitors",

abstract = "A series of peptide analogues of Ac-CIYKYY (1) were synthesized by functional group modifications in peptide side chains or by introducing conformational constraints, to improve the inhibitory potency against active Src kinase. Ac-CIYKF(4-NO2)Y (2, IC50 = 0.53 μM) and conformationally constrained peptide 31 (IC50 = 0.28 μM) exhibited 750- and 1400-fold higher inhibitory activities, respectively, versus that of 1 (IC50 = 400 μM). Compound 2 exhibited a partial competitive inhibition pattern against ATP.",

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T1 - Synthesis and structure-activity relationships of linear and conformationally constrained peptide analogues of CIYKYY as Src tyrosine kinase inhibitors

AU - Kumar, Anil

AU - Ye, Guofeng

AU - Wang, Yuehao

AU - Lin, Xiaofeng

AU - Sun, Gongqin

AU - Parang, Keykavous

PY - 2006/6/1

Y1 - 2006/6/1

N2 - A series of peptide analogues of Ac-CIYKYY (1) were synthesized by functional group modifications in peptide side chains or by introducing conformational constraints, to improve the inhibitory potency against active Src kinase. Ac-CIYKF(4-NO2)Y (2, IC50 = 0.53 μM) and conformationally constrained peptide 31 (IC50 = 0.28 μM) exhibited 750- and 1400-fold higher inhibitory activities, respectively, versus that of 1 (IC50 = 400 μM). Compound 2 exhibited a partial competitive inhibition pattern against ATP.

AB - A series of peptide analogues of Ac-CIYKYY (1) were synthesized by functional group modifications in peptide side chains or by introducing conformational constraints, to improve the inhibitory potency against active Src kinase. Ac-CIYKF(4-NO2)Y (2, IC50 = 0.53 μM) and conformationally constrained peptide 31 (IC50 = 0.28 μM) exhibited 750- and 1400-fold higher inhibitory activities, respectively, versus that of 1 (IC50 = 400 μM). Compound 2 exhibited a partial competitive inhibition pattern against ATP.

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JO - Journal of Medicinal Chemistry

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ER -

Synthesis and structure-activity relationships of linear and conformationally constrained peptide analogues of CIYKYY as Src tyrosine kinase inhibitors

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