Molecular architectures of glycosylated dendronized bottle brushes in action: Biocompatibility and anti-amyloidogenic activity of pseudo-glycodendrimers

Glycopolymers are versatile materials for biomedical and healthcare applications, e.g., as carrier and polymeric therapeutics. Especially, the topology and surface composition of such materials play a key role in being promising materials in the anti-amyloidogenic interventions. Herein, 2nd and 3rd generation of pseudo-glycodendrimers (<b>PGDs</b>), based on hyperbranched polyester core with different sugar decorations, are synthesized, characterized, and used to investigate their anti-amyloidogenic properties toward Aβ (1-40) and (1-42), key players in Alzheimerś disease. The findings reveal that <b>PGDs</b> have a dendronized bottle brush architecture, as determined by SAXS analysis. <b>PGDs</b> are capable of interfering with the aggregation process of Amyloid-β peptides due to the high degree of sugar functionalization on the outer surface and the specific molecular shape. Additionally, cell viability studies indicate that <b>PGDs</b> exhibit concentration-dependent biocompatibility. Importantly, it is demonstrated that <b>PGDs</b> can be multi-functionalized by various sugar molecules, dyes, and/or peptides in a final one-pot approach. These findings suggest that <b>PGDs</b> may offer new avenues for therapeutic research in neurodegenerative diseases. Finally, it should be noted that this kind of highly branched glycopolymers possesses a molecular shape of dendronized bottle brushes and not a globular perfectly branched structure like glycodendrimers, as originally postulated.