Three semi-synthetic approaches to a set of curdlan sulfate polysaccharides with different sulfation patterns

Fabiana Esposito¹Agnieszka Zabłocka²Serena Traboni¹Alfonso Iadonisi¹Sabina Górska²Emiliano Bedini^1*

• ¹University of Naples Federico II, Naples, Italy
• ²Instytut Immunologii i Terapii Doswiadczalnej im Ludwika Hirszfelda Polskiej Akademii Nauk, Wrocaw, Poland

Introduction: Curdlan is a linear homopolysaccharide composed of -1→3-linked glucose units. It is extracted from some bacteria as an exopolysaccharide, and employed in the food industry due to its remarkable rheological and thermal behaviors. Furthermore, its ability to form gel encapsulations with several drugs and its roles in innate and adaptive immunity have fueled an increasing interest in pharmaceutical applications of curdlan and derivatives thereof. Among them, curdlan sulfate derivatives disclosed not only a highly enhanced water solubility concerning native curdlan, but also an efficient immunomodulatory potential both in vitro and in vivo assays. Methods: To detect the effects of sulfation degree and sulfation pattern on the immunological activity of curdlan sulfate, a set of regioselectively sulfated curdlan polysaccharides has been semi-synthesized and fully characterized utilizing nuclear magnetic resonance (NMR) spectroscopy techniques. Results: Although some regioselectively sulfated curdlan derivatives were already reported some years ago, in this work a comprehensive semi-synthetic study has been developed, by investigating three different, complementary approaches based, respectively, on direct regioselective sulfation or desulfation reactions or multi-step protection-sulfation-deprotection procedures. Discussion: Some of the semi-synthesized curdlan sulfate derivatives were selected as representatives of different sulfation degrees and patterns and subjected to a panel of immunological assays to define some structure-activity relationships.