SH2-directed ligands of the Lck tyrosine kinase.
Two separate libraries, prepared via parallel synthesis, were employed to identify low-molecular-weight SH2-targeted ligands for the Lck tyrosine protein kinase. These libraries were constructed to furnish non-amino acid analogues of the (1) Glu-Glu and (2) Ile residues of the Lck SH2 domain peptide ligand Ac-pTyr-Glu-Glu-Ile-amide. The lead compound acquired in this study exhibits a dissociation constant for the Lck SH2 domain that is comparable to that displayed by Ac-pTyr-Glu-Glu-Ile-amide. These results demonstrate that the standard amino acid residues Glu-Glu-Ile can be completely replaced with non-amino acid moieties without loss of SH2 affinity.
Lee
T R
TR
Department of Biochemistry, The Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA.
Lawrence
D S
DS
D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques; D003374:Coumarins / Q000138:chemical synthesis* / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D008024:Ligands; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000737:chemistry*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D018909:src Homology Domains
D000577:Amides; D003374:Coumarins; D008024:Ligands; D014443:Tyrosine; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)