The synthesis of peptide-oligonucleotide conjugates by a fragment coupling approach

Abstract

Solid-phase synthesis of several peptide-oligonucleotide conjugates has been achieved using a peptide fragment coupling strategy on a controlled pore glass support. The conjugates contain either a hydrophobic tetrapeptide LGIG or an 8-residue basic peptide of the HIV-1 Tat protein coupled to one of two oligodeoxyribonucleotides, an oligoribonucleotide or a mixed ribo/2′- O-methyl oligonucleotide. Improved yields were obtained when internucleotide β-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 oligonucleotide.