Tunable multivalent Fe(II)-based glycoassemblies as mimetics for native high-mannose glycans.

Area of Science:

• Carbohydrate Chemistry
• Biophysical Chemistry
• Glycobiology

Background:

• High mannose glycans (HMGs) are crucial in biological processes like protein folding and immunity.
• Lectins bind HMGs via multivalent interactions, involving multiple sugars and lectin binding sites.

Purpose of the Study:

• To create chemically defined multivalent glycan displays using Fe(II) iminopyridine complexes.
• To investigate the interaction of these displays with monomeric Griffithsin (mGRFT) as a model lectin.
• To explore their potential as HMG mimetics and competitive inhibitors.

Main Methods:

• Synthesis of Fe(II) iminopyridine complexes with controlled glycan valency, arm length, and mannose display.
• Characterization of interactions using biolayer interferometry (BLI), isothermal titration calorimetry (ITC), and NMR spectroscopy.
• Systematic molecular modifications to tune binding affinity.

Main Results:

• Fe(II) glycan assemblies exhibited a >1000-fold range in binding affinity (K_D) with mGRFT.
• Binding affinity was tunable by altering saccharide tether length and the number of displayed sugars.
• Demonstrated the ability of these assemblies to mimic native HMGs.

Conclusions:

• Tunable Fe(II) glycan assemblies serve as effective mimetics for high mannose glycans.
• These assemblies can function as competitive inhibitors of native glycan binding by lectins.
• The study provides a platform for designing glycan-based molecules with controlled binding properties.