Binding of a series of synthetic multivalent carbohydrate analogs to the Man/Glc-specific lectins Con A and Dioclea grandiflora lectin was investigated by isothermal titrn. microcalorimetry. Dimeric analogs possessing terminal a-D-mannopyranoside residues, and di-, tri-, and tetrameric analogs possessing terminal 3,6-di-O-(a-D-mannopyranosyl)-a-D-mannopyranoside residues, which is the core trimannoside of asparagine-linked carbohydrates, were selected in order to compare the effects of low and high affinity analogs, resp. Exptl. conditions were found that prevented pptn. of the carbohydrate-lectin cross-linked complexes during the isothermal titrn. microcalorimetry expts. The results show that the value of n, the no. of binding sites on each monomer of the lectins, is inversely proportional to the no. of binding epitopes (valency) of each carbohydrate. Hence, n values close to 1.0, 0.50, and 0.25 were obsd. for the binding of mono-, di-, and tetravalent sugars, resp., to the two lectins. Importantly, differences in the functional valency of a triantennary analog for Con A and D. grandiflora lectin are obsd. The enthalpy of binding, DH, is obsd. to be directly proportional to the no. of binding epitopes in the higher affinity analogs. For example, DH of a tetravalent trimannoside analog is nearly four times greater than that of the corresponding monovalent analog. Increases in Ka values of the multivalent carbohydrates relative to monovalent analogs, known as the multivalency effect, are shown to be due to more pos. entropy (TDS) contributions to binding of the former sugars. A general thermodn. model for distinguishing binding of multivalent ligands to a single receptor with multiple, equal subsites vs. binding to sep. receptor mols. is given. [on SciFinder (R)]