Dynamic combinatorial chemistry (DCC) is a potentially useful method for the identification of biomacromolecule ligands; however, the number of reactions applicable to DCC in aqueous solution is limited. We report studies that investigate the reversible reaction of boronic acids with alcohols as an approach to enzyme inhibition, employing α-chymotrypsin as a model system. NMR techniques (¹¹B NMR and ¹H waterLOGSY) were used to observe ternary complexes of boronic acids, sugars and α-chymotrypsin, and were useful for distinguishing preferentially binding combinations of boronic acids and sugars. The results reveal that both the propensity of boronate ester formation in solution and affinity of the boronate ester for the target enzyme determine whether ternary complex formation is observed. The results also provide proof of principle for the boronate ester approach to DCC versusprotein targets.