Combined chemical and biosynthetic route to access a new apoptolidin congener.
Glycosylation of a synthetic aglycone using precursor-directed biosynthesis is facilitated by a chemical ketosynthase "knockdown" of the apoptolidin producer Nocardiopsis sp. This synthetic approach facilitated the preparation of an unnatural disaccharide derivative of apoptolidin D that substantially restores cytotoxicity against H292 cells and deconvolutes the role of the decorating sugars in apoptolidin bioactivity.
Ghidu
Victor P
VP
Department of Chemistry, Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee 37235, USA.
Ntai
Ioanna
I
Wang
Jingqi
J
Jacobs
Aaron T
AT
Marnett
Lawrence J
LJ
Bachmann
Brian O
BO
Sulikowski
Gary A
GA
D000190:Actinomyces / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006031:Glycosylation; D006801:Humans; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D018942:Macrolides; C518447:apoptolidin D