Protein Kinase C (PKC) plays a crucial role in signal transduction for a variety of biologically active substances which activate cellular functions and proliferation. Several classes of naturally occurring compounds including diacylglycerols, phorbol esters and indolactams have been shown to activate PKC. The last-named compounds include teleocidin B, lyngbyatoxin and indolactam V. Since none of these are readily available to researchers, the study of this class of activators has not progressed as rapidly as for the others. The proposed project will provide an efficient synthesis of a potent indolactam activator of PKC. This in turn will provide the research community with a reliable source of this class of activator at reasonable prices. The project will also develop a suitable substrate for the preparation of a (3H)-labeled indolactam activator of very high specific activity for use in receptor binding studies. The efficient synthesis will provide a starting material for further structural modifications which may lead to new indolactam-based compounds with altered and possibly useful biological properties.
