6] Preparation of vitamin B6-peptide and vitamin B6-peptide-oligonucleotide conjugates

Abstract

Publisher Summary This chapter describes the preparation of vitamin B 6 –peptide conjugates. The general approach is first to assemble the peptide and then append the pyridoxyl group, prior to cleavage from the solid support. The vitamin B 6 , conjugate of the peptide, ornithine-cysteinecarboxyamide, is synthesized with linkage through the δ -amino group of the ornithine residue. This peptide has been used as a model for a series of ( δ )-ornithine isopeptides that have been incorporated into oligonucleotide conjugates. The chapter also describes the preparation of vitamin B 6 –peptide–oligonucleotide conjugates. The general approach is to link the peptide via its cysteinyl thiol group to an oligonucleotide bearing a thiol-reactive functionality. The oligodeoxynucleotide is synthesized using a commercially available reagent that places a primary amine at the 5' terminus. Reaction of this primary amine with an active ester of iodoacetic acid thereby provides the thiol-reactive functionality for conjugation with the thiol group of the cysteine residue in the peptide.