Modifying the glycosidic linkage in digitoxin analogs provides selective cytotoxins.
A chemoselective reaction between oxyamines and unprotected, unactivated reducing sugars was used to construct for the first time a panel of linkage-diversified neoglycosides. This panel of digitoxin analogs included potent and selective tumor cytotoxins; cytotoxicity was dependent on the structure of the glycosidic linkage. These results validate linkage diversification through neoglycosylation as a unique and simple strategy to powerfully complement existing methods for the optimization of glycoconjugates.
Langenhan
Joseph M
JM
Department of Chemistry, Seattle University, 901 12th Avenue, Seattle, WA 98122, USA. langenha@seattleu.edu
Engle
Jeffery M
JM
Slevin
Lauren K
LK
Fay
Lindsay R
LR
Lucker
Ryan W
RW
Smith
Kyle R
KR
Endo
Matthew M
MM
D000588:Amines / Q000737:chemistry; D002241:Carbohydrates / Q000737:chemistry; D003603:Cytotoxins / Q000737:chemistry / Q000494:pharmacology*; D004074:Digitoxin / Q000031:analogs & derivatives* / Q000737:chemistry; D006001:Glycoconjugates / Q000737:chemistry; D006031:Glycosylation
D000588:Amines; D002241:Carbohydrates; D003603:Cytotoxins; D006001:Glycoconjugates; D004074:Digitoxin