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 language | English (US) |
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Pages (from-to) | 49-56 |
Number of pages | 8 |
Journal | Chemistry and Biology |
Volume | 3 |
Issue number | 1 |
DOIs | |
State | Published - 1996 |
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmacology
- Drug Discovery
- Clinical Biochemistry