Conjugation of Indoles to Antibodies through a Novel Self-Immolating Linker.
Chemistry
; 24(19): 4830-4834, 2018 Apr 03.
Article
de En
| MEDLINE
| ID: mdl-29493023
ABSTRACT
A novel strategy to attach indole-containing payloads to antibodies through a carbamate moiety and a self-immolating, disulfide-based linker is described. This new strategy was employed to connect a selective estrogen receptor down-regulator (SERD) to various antibodies in a site-selective manner. The resulting conjugates displayed potent, antigen-dependent down-regulation of estrogen receptor levels in MCF7-neo/HER2 and MCF7-hB7H4 cells. They also exhibited similar antigen-dependent modulation of the estrogen receptor in tumors when administered intravenously to mice bearing MCF7-neo/HER2 tumor xenografts. The indole-carbamate moiety present in the new linker was stable in whole blood from various species and also exhibited good inâ
vivo stability properties in mice.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Indoles
Limites:
Animals
/
Humans
Langue:
En
Journal:
Chemistry
Sujet du journal:
QUIMICA
Année:
2018
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique