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Multivalent chitobiose self-assembled glycostructures as ligands to lysozyme.
Bharat Singh Patel1, Shivender Yadav1, Avadhesha Surolia2
1Department of Organic Chemistry, Indian Institute of Science, Bangalore, India.
Bioorganic Chemistry
|December 5, 2024
Summary
Synthetic glycostructures with chitobiose bind strongly to lysozyme, showing pH sensitivity and enhanced binding constants. These multivalent structures also delay the enzyme
Area of Science:
- Biochemistry and Supramolecular Chemistry
- Glycobiology and Biomaterials
Background:
- Self-assembled glycostructures are crucial for understanding biological interactions.
- Chitobiose is a key component in biological recognition processes, particularly with enzymes like lysozyme.
- Developing multivalent glycostructures with tunable properties is essential for advanced applications.
Purpose of the Study:
- To synthesize and characterize pH-sensitive, self-assembled multivalent glycostructures containing chitobiose.
- To investigate the binding affinity and kinetics of these glycostructures with lysozyme.
- To evaluate the impact of multivalent binding on lysozyme's enzymatic activity.
Main Methods:
- Synthesis of glycolipid (GL) and lipid (L) components.
- Formation of self-assembled glycostructures with varying GL:L molar fractions.
- Characterization using dynamic light scattering (DLS) and solid-state microscopy.
- Binding studies with lysozyme to determine association/dissociation kinetics and equilibrium binding constants (Ka).
- Assessment of lysozyme's antimicrobial lytic activity in the presence of glycostructures.
Main Results:
- Uniform self-assembled glycostructures were successfully prepared.
- The structures exhibited pH-dependent disassembly due to ester linkage hydrolysis.
- Binding avidity to lysozyme increased with GL content, with 50% GL showing the highest affinity.
- Multivalent chitobiose glycostructures achieved Ka values 2-4 orders of magnitude higher than monomeric chitobiose.
- Complexation with glycostructures delayed lysozyme's lytic activity.
Conclusions:
- pH-sensitive multivalent chitobiose-containing glycostructures facilitate high-affinity lysozyme binding.
- Multivalent presentation significantly enhances equilibrium binding constants compared to monovalent interactions.
- Complexation modulates lysozyme's enzymatic function, delaying its lytic activity.
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