Peptide inhibitors of the mitogen-activated protein kinase pathway: A structure-mimetic peptide corresponding to the conserved inter-DFC-APE region in the kinase domain
Y. Fukami et al., Peptide inhibitors of the mitogen-activated protein kinase pathway: A structure-mimetic peptide corresponding to the conserved inter-DFC-APE region in the kinase domain, PHARM THERA, 82(2-3), 1999, pp. 399-407
The signal transduction pathway mediated by mitogen-activated protein kinas
es is an attractive target for the design of pharmacologically effective in
hibitors. Two specific cell permeant small molecule inhibitors of this path
way have been reported. However, under certain circumstances, nonpermeable
inhibitors, such as neutralizing antibodies and peptide inhibitors, are als
o useful. We present here a novel approach for such peptide inhibitor desig
n. The procedure is based on the synthesis of a structure mimetic peptide c
orresponding 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 an
tipeptide antibodies as probes for protein kinase regulation mechanisms is
also evaluated. (C) 1999 Elsevier Science Inc. All rights reserved.