EUR POLYM J 252, 114739: 1-10 (2026)

IF 6,3

Structural design of diblock glycopolymers modulates galectin affinity

Marina Rodrigues Tavares, Michaela Hovorková, Markéta Frejková, Vladimír Křen, Tomáš Etrych, Pavla Bojarová, Petr Chytil

 Abstract

Galectins are carbohydrate-binding proteins that have recently attracted considerable attention due to their vital role in cancer development and progression, and support of cancer cell survival. The two most common galectins, galectin-1 (Gal-1) and galectin-3 (Gal-3), are promising targets for therapeutic inhibition. Their carbohydratebinding affinities can be enhanced by exploiting the multivalency effect induced by multiple glycosylation binding sites. This study investigates diblock glycopolymers differing in carbohydrate ligand content and distribution along the polymer chain. Developed diblock glycopolymers take advantage of biocompatible and highly water-soluble N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers, which form the entire polymer backbone. The diblock presentation with a pristine HPMA block attached to the ligand-carrying block enabled the presentation of a high number of ligands while maintaining the favorable physicochemical properties of the backbone, which may have otherwise been compromised by a high ratio of ligand to backbone. Using a simple lactose or N-acetyllactosamine ligand, we identified the polymer design and the ratio of both polymer blocks that best enhanced binding affinity to Gal-1 or Gal-3. Our findings demonstrate that a well-designed glycopolymer structure featuring a basic ligand, such as lactose, can achieve performance comparable to that of higher-affinity ligands, emphasizing the crucial role of structural optimization in multivalent interactions. These results highlight the potential of tailored HPMA-based diblock glycopolymers as a platform for designing more effective drug-free nanomedicines that target and inhibit galectins in cancer therapy.

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