Template-directed ligation of peptides to oligonucleotides

Richard K. Bruick, Philip E. Dawson, Stephen B H Kent, Nassim Usman, Gerald F. Joyce

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Abstract

Background: Oligonucleotide-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 a carboxy-terminal thioester, were converted to thioester-linked oligonucleotide-peptide intermediates. The oligonucleotide 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. Conclusions: 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. antisense, oligonucleotide-peplide conjugate, template-directed ligation

Original languageEnglish (US)
Pages (from-to)49-56
Number of pages8
JournalChemistry and Biology
Volume3
Issue number1
Publication statusPublished - 1996

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ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Bruick, R. K., Dawson, P. E., Kent, S. B. H., Usman, N., & Joyce, G. F. (1996). Template-directed ligation of peptides to oligonucleotides. Chemistry and Biology, 3(1), 49-56.