Heptakis(6-amino-6-deoxy)-beta-cyclodextrin stabilizes the synthetic anticoagulant fondaparinux

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The intermolecular interactions between the cationic per-6-amino-b-CD with the highly anionic heparin analogue anticoagulant fondaparinux were studied at two different – physiological (pD 7.4) and acidic (pD 2.0) – pH values in a recently published study. Under both pH conditions strong electrostatic interactions were identified between the oppositely charged carbohydrates based on NMR studies. Under acidic conditions a thermodynamically stable (log b > 4.9), high-affinity system was described by extensive NMR experiments.

Under acidic condition, the degradation of fondaparinux was observed. It has been revealed by NMR and nESI-MS experiments that the degradation corresponds to the desulfation of the anticoagulant agent that involves one or two sulfate moieties.

It has been demonstrated that the heptacationic cyclodextrin – present in equimolar ratio – strongly inhibits the sulfate loss of fondaparinux, acting as a stabilizer. Thus, per-6-amino-b-CD offers an efficient strategy to study sulfated carbohydrates under acidic conditions without any sulfate loss. The finding of this research opens the floor for new applications of cationic CDs as glycosaminoglycan stabilizers.

Bianka Várnai, Márkó Grabarics, Zoltán Szakács, Kevin Pagel, Milo Malanga, Tamás Sohajda, Szabolcs Béni,
Structural characterization of fondaparinux interaction with per-6-amino-beta-cyclodextrin: An NMR and MS study, Journal of Pharmaceutical and Biomedical Analysis, 197, 2021, 113947,


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