Programmable synthesis of well-defined, glycosylated iron() supramolecular assemblies with multivalent protein-binding capabilities

• Published in: Chemical science (Cambridge) 2023-01, Vol.14 (4), p.118-126
• Main Authors: Schwab, Jake H, Bailey, Jake B, Gembicky, Milan, Stauber, Julia M
• Format: Article
• Language: English
• Subjects: Assemblies; Binding; Biological activity; Biological properties; Carbohydrates; Chemistry; Chemists; Concanavalin A; Iron; Maltose; Mannose; Modular construction; Principles; Proteins; Recognition; Self-assembly
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/d2sc05689e

Multivalency plays a key role in achieving strong, yet reversible interactions in nature, and provides critical chemical organization in biological recognition processes. Chemists have taken an interest in designing multivalent synthetic assemblies to both better understand the underlying principles governing these interactions, and to build chemical tools that either enhance or prevent such recognition events from occurring in biology. Rationally tailoring synthetic strategies to achieve the high level of chemical control and tunability required to mimic these interactions, however, is challenging. Here, we introduce a systematic and modular synthetic approach to the design of well-defined molecular multivalent protein-binding constructs that allows for control over size, morphology, and valency. A series of supramolecular mono-, bi-, and tetrametallic Fe( ii ) complexes featuring a precise display of peripheral saccharides was prepared through coordination-driven self-assembly from simple building blocks. The molecular assemblies are fully characterized, and we present the structural determination of one complex in the series. The mannose and maltose-appended assemblies display strong multivalent binding to model lectin, Concanavalin A ( K d values in μM), where the strength of the binding is a direct consequence of the number of saccharide units decorating the molecular periphery. This versatile synthetic strategy provides chemical control while offering an easily accessible approach to examine important design principles governing structure-function relationships germane to biological recognition and binding properties. A modular approach to the synthesis and design of well-defined molecular saccharide-functionalized multivalent assemblies that engage in protein binding.