Abstract
Using a uniquely promiscuous engineered glycosyltransferase (GT) derived from the macrolide-inactivating GT OleD, a single-step asymmetric glucosylation of one 'arm' of the drug mitoxantrone was efficiently achieved in high stereo- and regiospecificity. The synthesis, structural elucidation, and anticancer activity of the corresponding mitoxantrone 4'-β-D-glucoside are described.
Publication types
-
Research Support, N.I.H., Extramural
MeSH terms
-
Antineoplastic Agents / chemical synthesis*
-
Antineoplastic Agents / chemistry
-
Antineoplastic Agents / pharmacology
-
Drug Screening Assays, Antitumor
-
Female
-
Glucosides / chemical synthesis*
-
Glucosides / chemistry
-
Glucosides / pharmacology
-
Glucosyltransferases / metabolism
-
Glycosylation
-
Glycosyltransferases / metabolism*
-
Humans
-
K562 Cells
-
Mitoxantrone / analogs & derivatives*
-
Mitoxantrone / chemical synthesis
-
Mitoxantrone / chemistry*
-
Mitoxantrone / pharmacology
-
Protein Engineering
-
Stereoisomerism
Substances
-
Antineoplastic Agents
-
Glucosides
-
mitoxantrone 4'-beta-D-glucoside
-
Mitoxantrone
-
Glycosyltransferases
-
Glucosyltransferases
-
macrolide glycosyltransferase