title: Structure-based design of peptidomimetic antagonists of p56(lck) SH2 domain.
abstract: Starting from the tetrapeptide Ac-pYEEI-NHMe and using a structure-based approach, we have designed and synthesised a peptidomimetic ligand for p56(lck) SH2 domain containing a conformationally restricted replacement for the two glutamate residues. We have explored replacments for the isoleucine residue in the pY+3 pocket and thus identified 1-(R)-amino-3-(S)-indaneacetic acid as the most potent replacement. We also report the X-ray crystal structures of two of the antagonists.
authors: Roche Products Limited, 40 Broadwater Road, Welwyn Garden City, AL7 3AY, Hertfordshire, UK. chobbs@ionixpharma.com
authors: Christopher J
authors: CJ
authors: Hobbs
authors: Rino A
authors: RA
authors: Bit
authors: Andrew D
authors: AD
authors: Cansfield
authors: Bill
authors: B
authors: Harris
authors: Christopher H
authors: CH
authors: Hill
authors: Katherine L
authors: KL
authors: Hilyard
authors: Ian R
authors: IR
authors: Kilford
authors: Eric
authors: E
authors: Kitas
authors: Antonin
authors: A
authors: Kroehn
authors: Peter
authors: P
authors: Lovell
authors: David
authors: D
authors: Pole
authors: Paul
authors: P
authors: Rugman
authors: Brad S
authors: BS
authors: Sherborne
authors: Ian E D
authors: IE
authors: Smith
authors: David R
authors: DR
authors: Vesey
authors: D Lee
authors: DL
authors: Walmsley
authors: David
authors: D
authors: Whittaker
authors: Glyn
authors: G
authors: Williams
authors: Fiona
authors: F
authors: Wilson
authors: David
authors: D
authors: Banner
authors: Allan
authors: A
authors: Surgenor
authors: Neera
authors: N
authors: Borkakoti
mesh_terms: D000818:Animals; D006224:Cricetinae; D018360:Crystallography, X-Ray; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D018698:Glutamic Acid; D008024:Ligands; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000037:antagonists & inhibitors* / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D018909:src Homology Domains
chemical_list: D004791:Enzyme Inhibitors; D008024:Ligands; D009842:Oligopeptides; D018698:Glutamic Acid; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)