The binding of boronated peptides to low affinity mammalian saccharides

A 54‐member library of boronated octapeptides, with all but the boronated residue being proteinogenic, was tested for affinity to a set of saccharides commonly found on the terminus of mammalian glycans. After experimentation with a high‐throughput dye‐displacement assay, attention was focused on isothermal titration calorimetry as a tool to provide reliable affinity data, including enthalpy and entropy of binding. A small number of boronated peptides showed higher affinity and significant selectivity for N‐ acetylneuraminic acid over methyl‐α‐ d ‐galactopyranoside, methyl‐α/β‐ l ‐fucopyranoside and N‐ acetyl‐ d ‐glucosamine. Thermodynamic data showed that for most of the boronated peptides studied, saccharide binding was associated with a significant increase in entropy, presumably resulting from the displacement of semiordered water molecules from around the sugar and/or peptide.