Tunable structure of chimeric isomaltomegalosaccharides with double -(1 4)-glucosyl chains enhances the solubility of water-insoluble bioactive compounds

Isomaltomegalosaccharides with alpha-(1 -> 4) and alpha-(1 -> 6)-segments solubilize water-insoluble ligands since the former complexes with the ligand and the latter solubilizes the complex. Previously, we enzymatically synthe-sized isomaltomegalosaccharide with a single alpha-(1 -> 4)-segment at the reducing end (S-IMS) by dextran dex-trinase (DDase), but the chain length [average degree of polymerization (DP) <= 9] was insufficient for strong encapsulation. We hypothesized that the conjugation of longer alpha-(1 -> 4)-segment afforded the promising function although DDase is incapable to do so. In this study, the cyclodextrin glucanotransferase-catalyzed coupling reaction of alpha-cyclodextrin to S-IMS synthesized a new alpha-(1 -> 4)-segment at the nonreducing end (N -4S) of S-IMS to form D-IMS [IMS harboring double alpha-(1 -> 4)-segments]. The length of N-4S was modulated by the ratio between alpha-cyclodextrin and S-IMS, generating N-4Ss with DPs of 7-50. Based on phase-solubility analysis, D-IMS-28.3/13/3 bearing amylose-like helical N-4S with DP of 28.3 displayed a water-soluble com-plex with aromatic drugs and curcumin. Small-angle X-ray scattering revealed the chain adapted to rigid in solution in which the radius of gyration was estimated to 2.4 nm. Furthermore, D-IMS with short N-4S solubilized flavonoids of less-soluble multifunctional substances. In our research, enzyme-generated functional biomaterials from DDase were developed to maximize the hydrophobic binding efficacy towards water-insoluble bioactive compounds.