Structural basis for the activity of pp60c-src protein tyrosine kinase inhibitors

Ninad V. Prabhu, Subeeh A. Siddiqui, John S. McMurray, Bernard Pettitt

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Conformational searches on three closely related pp60c-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.

Original languageEnglish (US)
Pages (from-to)167-179
Number of pages13
JournalBiopolymers
Volume59
Issue number3
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

src-Family Kinases
Protein Kinase Inhibitors
Conformations
Proteins
Peptides
Thermodynamics
Geometry
Testing

Keywords

  • β-turn
  • Antiparallel β-sheet
  • Backbone conformation
  • Cyclic analogue
  • Linear peptide
  • pp protein tyrosine kinase inhibitors

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Biophysics

Cite this

Structural basis for the activity of pp60c-src protein tyrosine kinase inhibitors. / Prabhu, Ninad V.; Siddiqui, Subeeh A.; McMurray, John S.; Pettitt, Bernard.

In: Biopolymers, Vol. 59, No. 3, 2001, p. 167-179.

Research output: Contribution to journalArticle

Prabhu, Ninad V. ; Siddiqui, Subeeh A. ; McMurray, John S. ; Pettitt, Bernard. / Structural basis for the activity of pp60c-src protein tyrosine kinase inhibitors. In: Biopolymers. 2001 ; Vol. 59, No. 3. pp. 167-179.
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