BBackground

Oligonucelotide-peptide conjugates have several applications, including their potential use as therapeutic agents. We developed a strategy for the chemical ligation of unprotected peptides to oligonucleotides in aqueous solution. The two compounds are joined via a stable amide bond in a template-directed reaction.

Results

Peptides, ending in carboxy-terminal thioester, were converted to thioester-linked oligonucleotide-peptide intermediates. The oligonucleatide portion of the intermediate binds to a complementary oligonucleotide template, placing the peptide in close proximity to an adjacent template-bound oligonucleotide that terminates in a 3 ' amine. The ensuing reaction results in the efficient formation of an amide-linked oligonucleotide-peptide conjugate.

Conclusion

An oligonucleotide template can be used to direct the ligation of peptides to oligonucleotides via a highly stable amide linkage. The ligation reaction is sequence specific, allowing the simultaneous ligation of multiple oligonucleotide-peptide pairs.