DIFFERENTIAL INHIBITION OF EUKARYOTE PROTEIN-KINASES BY CONDENSED TANNINS

Condensed tannins, isolated from a variety of plant sources, were char acterized according to the constituent flavans, being based on procyan idin and/or prodelphinidin and having a cis or trans stereochemistry a t positions 2 and 3. All the tannin preparations are potent inhibitors of rat liver cyclic AMP-dependent protein kinase catalytic subunit (c AK) with IC50 values (concentrations for 50% inhibition) ranging from 0.009 to 0.2 mu M. The tannin preparations are very good inhibitors of rat brain Ca2+- and phospholipid-dependent protein kinase C (PKC) (IC 50 values in the range 0.3-7 mu M), wheat embryo Ca2+-dependent protei n kinase (CDPK) (IC50 values in the range 0.8-7 mu M) and of calmoduli n (CaM)-dependent myosin light chain kinase (MLCK) (IC50 values in the range 7-24 mu M). One of the most effective preparations, that from t he leaves of Ribes nigram, has IC50 values with respect to cAK, PKC, C DPK and MLCK of 0.009, 0.6, 2.0 and 16 mu M, respectively. In general, the order with respect to sensitivity to inhibition by these condensed tannins is cAK > PKC > CDPK > MLCK. The Ribes nigrum preparation is a competitive inhibitor of cAK with respect to both ATP and synthetic p eptide substrate. These condensed tannin preparations are the most pot ent plant-derived inhibitors of cAK yet found. Copyright (C) 1996 Else vier Science Ltd.