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Structural basis for the activity of pp60 c‐src protein tyrosine kinase inhibitors
Author(s) -
Prabhu Ninad V.,
Siddiqui Subeeh A.,
McMurray John S.,
Pettitt B. Montgomery
Publication year - 2001
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/1097-0282(200109)59:3<167::aid-bip1016>3.0.co;2-l
Subject(s) - antiparallel (mathematics) , chemistry , pharmacophore , stereochemistry , proto oncogene tyrosine protein kinase src , peptide , tyrosine , side chain , tyrosine kinase , beta sheet , peptide conformation , biochemistry , kinase , receptor , organic chemistry , physics , polymer , quantum mechanics , magnetic field
Conformational searches on three closely related pp60 c‐src protein tyrosine kinase inhibitors of varying potencies were performed to determine a structural basis for their activity. The first was a linear peptide (PDNEYAFFQf), the second its 10‐membered cyclic analogue, and the third a cyclic analogue with a para carboxyphenylalanine in place of one the F residues. A common backbone conformation with an antiparallel β‐sheet‐like geometry capped by similar β‐turns was found for all three peptides, which may be a binding conformation and gives a candidate pharmacophore for further testing. The interaction between some polar side chains and between some of the aromatic rings may be important for maintaining the correct conformation. The differences in potencies of these inhibitors may be attributed to certain thermodynamic and chemical reasons. © 2001 John Wiley & Sons, Inc. Biopolymers 59: 167–179, 2001