LacNAc (Galβ4GlcNAc) is a typical carbohydrate ligand of galectins - human lectins regulating, e.g., intercellular communication, adhesion and signaling . Human galectins participate in a number of pathologies including cancerogenesis, metastatic formation, inflammation or fibrosis. Therefore, they are prospective targets for therapeutical applications where selectivity for one particular galectin is highly desirable.
In the present study we synthesized a series of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers decorated with LacNAc epitope in various concentrations and architectures. The functionalized LacNAc disaccharide was prepared by enzymatic synthesis catalyzed by β-galactosidase from Bacillus circulans . In a structure-affinity relationship study we compare the difference in affinity between LacNAc distributed statistically on the polymer backbone or nested on bi- and trivalent phenyl branches. The affinity of prepared glycopolymers to galectins was determined in ELISA-type assay. We conclude that the manner of the LacNAc presentation on the HPMA copolymer brings a clear discrimination between galectins, reaching affinity in nanomolar range. The prepared selective glycopolymers are attractive for in vivo use due to their good water solubility and lack of toxicity and immunogenicity .
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