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