Peptide inhibitors of the mitogen-activated protein kinase pathway: a structure -mimetic peptide corresponding to the conserved inter-DFG-APE region in the kinase domain.
The signal transduction pathway mediated by mitogen-activated protein kinases is an attractive target for the design of pharmacologically effective inhibitors. Two specific cell-permeant small molecule inhibitors of this pathway have been reported. However, under certain circumstances, nonpermeable inhibitors, such as neutralizing antibodies and peptide inhibitors, are also useful. We present here a novel approach for such peptide inhibitor design. The procedure is based on the synthesis of a structure-mimetic peptide corresponding to a short peptide segment in the target molecule. The results obtained so far show that a peptide designed in such a way is an effective inhibitor of the pathway. The possible application of such peptides and antipeptide antibodies as probes for protein kinase regulation mechanisms is also evaluated.
Fukami
Y
Y
Biosignal Research Center and Graduate School of Science and Technology, Kobe University, Nada, Japan.
Tokmakov
A A
AA
Konaka
K
K
Sato
K
K
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology; D001665:Binding Sites / Q000276:immunology / Q000502:physiology; D005544:Forecasting; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000276:immunology; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*
D000906:Antibodies; D010455:Peptides; D020929:Mitogen-Activated Protein Kinase Kinases