Prooligonucleotides exhibit less serum-protein binding than phosphodiesterand phosphorothioate oligonucleotides

The protein-binding properties of dodecathymidine derivatives (prooligos) b earing either methyl- or tert-butyl-S-acylthioethyl (Me- or tBuSATE) protec ting groups were evaluated. The dissociation constants (Kd) were estimated for complexes of prooligos with serum blood proteins and lactoferrin using prooligos to compete the binding of the radiolabeled, alkylating probe olig onucleotide CIRp(T)(12) with the proteins. tBuSATE and MeSATE prooligos hav e decreased affinity of binding with serum proteins and lactoferrin compare d with their parent oligos. These data suggest that prooligos should cause less side effects which combined with their stability to nucleases and enha nced permeability into cells make them potentially useful for design of the rapeutics.