Alternative procedures for the synthesis of methionine-containing peptide-oligonucleotide hybrids

The synthesis of methionine-containing peptide-oligonucleotide hybrids has been found to be best accomplished by a stepwise solid-phase approach in wh ich peptide assembly using the sulfoxide derivative of methionine is follow ed by elongation of the oligonucleotide chain using the phosphite triester methodology, ammonia deprotection, and reduction of the sulfoxide to thioet her by reaction with N-methylmercaptoacetamide. Quantitative amino acid inc orporation yields could not always be achieved when the order of assembly o f the two moieties was reversed, i.e. by elongating the peptide chain on a resin-linked oligonucleotide in order to avoid exposure of the thioether fu nction to oxidizing conditions.