title: Template-directed ligation of peptides to oligonucleotides.
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.
authors.affiliation: The Scripps Research Institute, 10666 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: R K
authors.initials: RK
authors.lastname: Bruick
authors.forename: P E
authors.initials: PE
authors.lastname: Dawson
authors.forename: S B
authors.initials: SB
authors.lastname: Kent
authors.forename: N
authors.initials: N
authors.lastname: Usman
authors.forename: G F
authors.initials: GF
authors.lastname: Joyce
mesh_terms: D000577:Amides / Q000737:chemistry; D013058:Mass Spectrometry; D009841:Oligonucleotides / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D013698:Templates, Genetic
chemical_list: D000577:Amides; D009841:Oligonucleotides; D010455:Peptides