Synthesis Of Thio-containing Pyranosides And Their Binding Affinity Analysis To Con A By QCM

Carbohydrate/protein interactions are crucially important in many biological processes,and thus have been greatly concerned. To investigate those interactions, both variouscarbohydrate targets mainly supplied by carbohydrate synthesis, and powerful analysismethods, such as SPR, ITC, QCM and so on, are indispensable. Thio-containing glycosidesare often applied in the synthesis of oligosaccharides. Many of them have been directlyused as drugs or as potential therapeutic prototypes in the treatment of a variety ofpathological conditions. More importantly, thio-containing glycosides have greatadvantages when applied in Dynamic Combinatorial Chemistry (DCC) since they can offera consequent set of reversible reactions at very mild conditions. Thus, synthesis ofthio-containing glycosides and investigation of their interactions to proteins are ofconsiderable current research interests.In the present studies, by the application of double parallel and double serial inversion, thiolanalogs of D-pyranosides were efficiently synthesized. With the combination of otherdeveloped synthetic methods,9thiol analogs of D-mannopyranosides were finally acquired.The protein recognition properties of these9thio-containing mannosides were thenevaluated in a competition binding assay with the model lectin Con A by QCM. EC50valueswere estimated by non-linear regression. To our surprise, Methyl α-D-mannopyranosidedisplayed significant lower binding affinity towards Con A than its2-thio analog. Resultswere in agreement with known binding affinities where the4-thio-analog,6-thio-analogand β-D-derivatives of Methyl α-D-mannopyranoside are ineffective.3-thio-analog showsslightly lower binding affinities.