INHIBITION OF PROTEIN-TYROSINE KINASE-ACTIVITY IN INTACT-CELLS BY THEAPTAMERIC ACTION OF OLIGODEOXYNUCLEOTIDES

Direct interaction of oligodeoxynucleotides (ODNs) with proteins repre sents one of the nonantisense-mediated effects of ODNs. Phosphorothioa te-capped ODNs have been shown to inhibit directly the in vitro kinase activity of the chronic myelogenous leukemia-associated protein-tyros ine kinase p210(bcr-abl). In this study we have determined the efficac y of this aptameric ODN in a cellular system using the K562 chronic my elogenous leukemia-derived cell line, Significant effects upon cellula r phosphotyrosine content, as well as cellular growth in soft agar, ar e observed. These effects are sequence specific and are not mediated t hrough changes in p2l0(bcr-abl) protein levels. Additional ODNs are de scribed that also reduce cellular phosphotyrosine levels and inhibit g rowth in soft agar but do not inhibit p210(bcr-abl) kinase activity in vitro.