ISOZYME-SPECIFIC INHIBITION OF PROTEIN-KINASE-C BY RNA APTAMERS

In vitro selection technology has been used to purify RNA aptamers fro m a random sequence pool that can bind to, and specifically inhibit, p rotein kinase C beta IL. Two of the selected RNA aptamers bind to this isozyme of protein kinase C with nanomolar affinities and inhibit act ivation with unprecedented selectivity; the highly related, alternativ ely spliced beta I isozyme, which differs by 23 residues, is inhibited with 1 order of magnitude lower potency; the next most similar isozym e, alpha, shows no detectable inhibition. The production of isozyme-sp ecific inhibitors of protein kinase C opens the possibilities for diss ecting the roles of specific protein kinase Cs in the myriad of intrac ellular signaling pathways.