Oligonucleotide Bioconjugation with Bifunctional Palladium Reagents.
Angew Chem Int Ed Engl
; 60(21): 12109-12115, 2021 05 17.
Article
en En
| MEDLINE
| ID: mdl-33730425
ABSTRACT
Organometallic reagents enable practical strategies for bioconjugation. Innovations in the design of water-soluble ligands and the enhancement of reaction rates have allowed for chemoselective cross-coupling reactions of peptides and proteins to be carried out in water. There are currently no organometallic-based methods for oligonucleotide bioconjugation to other biomolecules. Here we report bifunctional palladium(II)-oxidative addition complexes (OACs) as reagents for high-yielding oligonucleotide bioconjugation reactions. These bifunctional OACs react chemoselectively with amine-modified oligonucleotides to generate the first isolable, bench stable oligonucleotide-palladium(II) OACs. These complexes undergo site-selective C-S arylation with a broad range of native thiol-containing biomolecules at low micromolar concentrations in under one hour. This approach provided oligonucleotide-peptide, oligonucleotide-protein, oligonucleotide-small molecule, and oligonucleotide-oligonucleotide conjugates in >80 % yield and afforded conjugation of multiple copies of oligonucleotides onto a monoclonal antibody.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Oligonucleótidos
/
Compuestos Organometálicos
/
Reactivos de Enlaces Cruzados
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos