Synthesis and Characterization of Oligonucleotide Peptides

Article abstract of DOI:10.1021/jo00009a044

The transport and reactivity of oligonucleotides may be altered by attaching pendant peptides, and it is of interest to develop general synthetic methods for such bioconjugates.Two protecting group strategies are described for the synthesis of nucleotide peptides containing a lysine residue.The preparation of a lysine-nucleopeptide phosphoramidite reagent is described, along with its use in solid-phase DNA synthesis.Di- and trinucleotides were prepared with pendant and extensively characterized by NMR.These studies showed the peptide side chains to have survived DNA synthesis conditions; we then incorporated nucleopeptide residues into longer oligonucleotides.A similar approach is described for the preparation of oligonucleotide histidines.Previously reported histidine-nucleopeptides serve as precursors to phosphoramidites and to phosphodiester DNA building blocks.Both solution- and solid-phase techniques are presented for the preparation of histidine-containing oligonucleotides.The methodology developed here allows the incorporation of nucleopeptide residues at internal positions in a DNA sequence, using standard reagents.We present a complete description of the synthesis, purification and characterization (via mass spectral and NMR methods) of the novel compounds.