Preparation of vitamin B6-conjugated peptides at the amino terminus and of vitamin B6-peptide-oligonucleotide conjugates.

A series of N-(4'-pyridoxyl)peptides has been made by standard Fmoc chemistry and a solid-phase coupling procedure. The last Fmoc group of the peptide was removed on the synthesizer, and the free amino group was then condensed with pyridoxal. The Schiff base formed was selectively reduced using sodium cyanoborohydride. The product was cleaved from the resin using a standard procedure. No deleterious effects were found when using the protected amino acids Fmoc-L-Ala, Fmoc-L-Arg(Pmc), Fmoc-L-Asp(OtBu), Fmoc-L-His(Trt), Fmoc-L-Ser(tBu), Fmoc-L-Thr(tBu), and Fmoc-L-Cys(Trt) for peptide synthesis. A vitamin B6-peptide-oligonucleotide conjugate could be synthesized using a cysteinyl peptide and a suitably activated oligonucleotide.