Probing Disaccharide Binding to Triplatin as Models for Tumor Cell Heparan Sulfate (GAG) Interactions

In this study, we have used [1H, 15N] NMR spectroscopy to investigate the interactions of the trinuclear platinum anticancer drug triplatin (1) (1,0,1/t,t,t or BBR3464) with site-specific sulfated and carboxylated disaccharides. Specifically, the disaccharides GlcNS­(6S)-GlcA (I) and GlcNS­(6S)-IdoA...

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Published in:Inorganic chemistry 2023-08, Vol.62 (33), p.13212-13220
Main Authors: Gorle, Anil K., Malde, Alpeshkumar K., Chang, Chih-Wei, Rajaratnam, Premraj, von Itzstein, Mark, Berners-Price, Susan J., Farrell, Nicholas P.
Format: Article
Language:English
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Summary:In this study, we have used [1H, 15N] NMR spectroscopy to investigate the interactions of the trinuclear platinum anticancer drug triplatin (1) (1,0,1/t,t,t or BBR3464) with site-specific sulfated and carboxylated disaccharides. Specifically, the disaccharides GlcNS­(6S)-GlcA (I) and GlcNS­(6S)-IdoA­(2S) (II) are useful models of longer-chain glycosaminoglycans (GAGs) such as heparan sulfate (HS). For both the reactions of 15N-1 with I and II, equilibrium conditions were achieved more slowly (65 h) compared to the reaction with the monosaccharide GlcNS­(6S) (9 h). The data suggest both carboxylate and sulfate binding of disaccharide I to the Pt with the sulfato species accounting for
ISSN:0020-1669
1520-510X
1520-510X
DOI:10.1021/acs.inorgchem.3c01391