Tailoring Metallosupramolecular Glycoassemblies for Enhancing Lectin Recognition

Multivalency is a fundamental principle in nature that leads to high-affinity intermolecular recognition through multiple cooperative interactions that overcome the weak binding of individual constituents. For example, multivalency plays a critical role in lectin-carbohydrate interactions that participate in many essential biological processes. Designing high-affinity multivalent glycoconjugates that engage lectins results in systems with the potential to disrupt these biological processes, offering promising applications in therapeutic design and bioengineering. Here, a versatile and tunable synthetic platform for the synthesis of metallosupramolecular glycoassemblies is presented that leverages subcomponent self-assembly, which employs metal ion templates to generate complex supramolecular architectures from simple precursors in one pot. Through ligand design, this approach provides precise control over molecular parameters such as size, shape, flexibility, valency, and charge, which afforded a diverse family of well-defined hybrid glyconanoassemblies. Evaluation of these complexes as multivalent binders to Concanavalin A (Con A) by isothermal titration calorimetry (ITC) demonstrates the optimal saccharide tether length and the effect of electrostatics on protein affinity, revealing insights into the impact of synthetic design on molecular recognition. The presented studies offer an enhanced understanding of structure-function relationships governing lectin-saccharide interactions at the molecular level and guide a systematic approach towards optimizing glyconanoassembly binding parameters.