Sterically Shielded, Stabilized Nitrile Imine for Rapid Bioorthogonal Protein Labeling in Live Cells.
J Am Chem Soc
; 140(14): 4860-4868, 2018 04 11.
Article
em En
| MEDLINE
| ID: mdl-29565582
ABSTRACT
In pursuit of fast bioorthogonal reactions, reactive moieties have been increasingly employed for selective labeling of biomolecules in living systems, posing a challenge in attaining reactivity without sacrificing selectivity. To address this challenge, here we report a bioinspired strategy in which molecular shape controls the selectivity of a transient, highly reactive nitrile imine dipole. By tuning the shape of structural pendants attached to the ortho position of the N-aryl ring of diaryltetrazoles-precursors of nitrile imines, we discovered a sterically shielded nitrile imine that favors the 1,3-dipolar cycloaddition over the competing nucleophilic addition. The photogenerated nitrile imine exhibits an extraordinarily long half-life of 102 s in aqueous medium, owing to its unique molecular shape that hinders the approach of a nucleophile as shown by DFT calculations. The utility of this sterically shielded nitrile imine in rapid (â¼1 min) bioorthogonal labeling of glucagon receptor in live mammalian cells was demonstrated.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Coloração e Rotulagem
/
Receptores de Glucagon
/
Iminas
/
Nitrilas
Limite:
Humans
Idioma:
En
Revista:
J Am Chem Soc
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos