biostudies-literatureZhang JNational Institute of Allergy and Infectious DiseasesNational Center for Advancing Translational SciencesNCATS NIH HHSNIAID NIH HHSNational Cancer Institute1053-8https://www.ebi.ac.uk/biostudies/studies/S-EPMC4601055biostudies-literatureUnknown6(10)The synthesis of a set of digitoxigenin neogluco/xylosides and corresponding study of their anticancer SAR revealed sugar amine regiochemistry has a dramatic effect upon activity. Specifically, this study noted sugar 3-amino followed by 4-amino-substitution to be most advantageous where the solvent accessibility of the appended amine within neoglycoside-Na(+),K(+)-ATPase docked models correlated with increased anticancer potency. This study presents a preliminary model for potential further warhead optimization in the context of antibody-directed steroidal glycosides and extends the demonstrated compatibility of aminosugars in the context of neoglycosylation.ACS medicinal chemistry lettersInfluence of Sugar Amine Regiochemistry on Digitoxigenin Neoglycoside Anticancer Activity.PMC4601055UL1TR000117R37 AI052218UL1 TR000117R37 AI52218Zhang JThorson JSZhan CGNandurkar NSFang LPonomareva LVYuan YfalseInfluence of Sugar Amine Regiochemistry on Digitoxigenin Neoglycoside Anticancer Activity.The synthesis of a set of digitoxigenin neogluco/xylosides and corresponding study of their anticancer SAR revealed sugar amine regiochemistry has a dramatic effect upon activity. Specifically, this study noted sugar 3-amino followed by 4-amino-substitution to be most advantageous where the solvent accessibility of the appended amine within neoglycoside-Na(+),K(+)-ATPase docked models correlated with increased anticancer potency. This study presents a preliminary model for potential further warhead optimization in the context of antibody-directed steroidal glycosides and extends the demonstrated compatibility of aminosugars in the context of neoglycosylation.2015-01-01T00:00:00Z2015 Oct2026-05-03T00:26:39.947Z2025-06-01T12:01:57.374ZS-EPMC46010552648791110.1021/acsmedchemlett.5b00120