1 research outputs found
High Affinity Glycodendrimers for the Lectin LecB from Pseudomonas aeruginosa
Following an iterative oxime ligation
procedure, cyclopeptide (R)
and lysine-based dendron (D) were combined in all possible arrangements
and successively functionalized with α-fucose and β-fucose
to provide a new series of hexadecavalent glycosylated scaffolds (i.e.,
scaffolds RD<sub>16</sub>, RR<sub>16</sub>, DR<sub>16</sub>, and DD<sub>16</sub>). These compounds and smaller analogs (tetra- and hexavalent
scaffolds R<sub>4</sub> and R<sub>6</sub>) were used to evaluate the
influence of the ligand valency and architecture, and of the anomer
configuration in the binding to the αFuc-specific lectin LecB
from Pseudomonas aeruginosa. Competitive
enzyme-linked lectin assays (ELLA) revealed that only the RD<sub>16</sub> architecture displaying αFuc (<b>9A</b>) reaches strong
binding improvement (IC<sub>50</sub> of 0.6 nM) over αMeFuc,
and increases the α-selectivity of LecB. Dissociation constant
of 28 nM was measured by isothermal titration micorcalorimetry (ITC)
for <b>9A</b>, which represents the highest affinity ligand
ever reported for LecB. ITC and molecular modeling suggested that
the high affinity observed might be due to an aggregative chelate
binding involving four sugar head groups and two lectins. Interestingly,
unprecedented binding effects were observed with β-fucosylated
conjugates, albeit being less active than the corresponding ligands
of the αFuc series. In particular, the more flexible lysine-based
dendritic structures (<b>15B</b> and <b>18B</b>) showed
a slight inhibitory enhancement in comparison with those having cyclopeptide
core