Template-directed ligation of peptides to oligonucleotides

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

Research output: Contribution to journalArticle

74 Citations (Scopus)

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
StatePublished - 1996

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Oligonucleotides
Ligation
Peptides
Amides
Antisense Oligonucleotides
Therapeutic Uses
Amines

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.

Template-directed ligation of peptides to oligonucleotides. / Bruick, Richard K.; Dawson, Philip E.; Kent, Stephen B H; Usman, Nassim; Joyce, Gerald F.

In: Chemistry and Biology, Vol. 3, No. 1, 1996, p. 49-56.

Research output: Contribution to journalArticle

Bruick, RK, Dawson, PE, Kent, SBH, Usman, N & Joyce, GF 1996, 'Template-directed ligation of peptides to oligonucleotides', Chemistry and Biology, vol. 3, no. 1, pp. 49-56.
Bruick RK, Dawson PE, Kent SBH, Usman N, Joyce GF. Template-directed ligation of peptides to oligonucleotides. Chemistry and Biology. 1996;3(1):49-56.
Bruick, Richard K. ; Dawson, Philip E. ; Kent, Stephen B H ; Usman, Nassim ; Joyce, Gerald F. / Template-directed ligation of peptides to oligonucleotides. In: Chemistry and Biology. 1996 ; Vol. 3, No. 1. pp. 49-56.
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