THE SYNTHESIS OF PEPTIDE-OLIGONUCLEOTIDE CONJUGATES BY A FRAGMENT COUPLING APPROACH

Solid-phase synthesis of several peptide-oligonucleotide conjugates ha s been achieved using a peptide fragment coupling strategy on a contro lled pore glass support. The conjugates contain either a hydrophobic t erapeptide LGIG or an 8-residue basic peptide of the HIV-1 Tat protein coupled to one of two oligodeoxyribonucleotides, an oligoribonucleoti de or a mixed ribo/2'-O-methyl oligonucleotide. Improved yields were o btained when internucleotide beta-cyanoethyl groups were removed from the support-bound oligonucleotide prior to peptide fragment coupling, and by use of a long alkyl spacer in the linkage between peptide and o ligonucleotide. (C) 1998 Published by Elsevier Science Ltd. All rights reserved.