Oligonucleotide conjugated to linear and branched high molecular weight polyethylene glycol as substrates for RNase H.

Two conjugates of an anti-HIV oligonucleotide (ODN) with different high mol ecular weight monomethoxy polyethylene glycols (MPEGs) have been tested for their activity as substrate towards RNase H. The MPEG does not impede the formation of the regular hybrid duplex with the target RNA sequence as poin ted out by the persistence of the RNase H activity; thus, these derivatives stimulate the hydrolysis of RNA by the enzyme at the same site and with th e same extent of cleavage as the native sequence.