Peptide-Oligonucleotide Hybrids with N-Acylphosphoramidate Linkages

Article abstract of DOI:10.1021/jo00120a032

The preparation of a peptide-oligonucletide hybrid with an N-acylphospkoramidate linkage has been carried out by (i) phosphitylation of the C-terminal carboxamide of a protected peptide by reaction with a chloroalkoxy(dialkylamino)phosphine in the presence of a base, (ii) coupling of the resulting N-acylphosphorodiamidite onto an oligonucleotide-resin followed by oxidation, and (iii) deprotection and cleavage under basic conditions.The synthetic method takes advantage of the unprecedented reaction of primary carboxamides with electrophilic P(III) species and takes place under mild conditions which are compatible with the stability of both the peptide and the oligonucleotide components.