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J. Biol. Chem., Vol. 269, Issue 51, 32051-32054, Dec, 1994

Isozyme-specific inhibition of protein kinase C by RNA aptamers

R Conrad, LM Keranen, AD Ellington and AC Newton
Department of Chemistry, Indiana University, Bloomington 47405.

In vitro selection technology has been used to purify RNA aptamers from a random sequence pool that can bind to, and specifically inhibit, protein kinase C beta II. Two of the selected RNA aptamers bind to this isozyme of protein kinase C with nanomolar affinities and inhibit activation with unprecedented selectivity; the highly related, alternatively spliced beta I isozyme, which differs by 23 residues, is inhibited with 1 order of magnitude lower potency; the next most similar isozyme, alpha, shows no detectable inhibition. The production of isozyme-specific inhibitors of protein kinase C opens the possibilities for dissecting the roles of specific protein kinase Cs in the myriad of intracellular signalling pathways.
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