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Pharmacol Ther. 1999 May-Jun;82(2-3):399-407.

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.

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  • 1Biosignal Research Center and Graduate School of Science and Technology, Kobe University, Nada, Japan.

Abstract

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.

PMID:
10454215
[PubMed - indexed for MEDLINE]
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