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The complex distribution of functional groups in carbohydrates, coupled with their strong solvation in water, makes them challenging targets for synthetic receptors. Despite extensive research into various molecular frameworks, most synthetic carbohydrate receptors have exhibited low affinities, and their interactions with sugars in aqueous environments remain poorly understood. In this work, we present a simple pyridinium-based hydrogen-bonding receptor derived from a subtle structural modification of a well-known tetralactam macrocycle. This small structural change resulted in a dramatic enhancement of glucose binding affinity, increasing from 56 M−1 to 3001 M−1. Remarkably, the performance of our synthetic lectin surpasses that of the natural lectin, concanavalin A, by over fivefold. X-ray crystallography of the macrocycle–glucose complex reveals a distinctive hydrogen bonding pattern, which allows for a larger surface overlap between the receptor and glucose, contributing to the enhanced affinity. Furthermore, this receptor possesses allosteric binding sites, which involve chloride binding and trigger receptor aggregation. This unique allosteric process reveals the critical role of structural flexibility in this hydrogen-bonding receptor for the effective recognition of sugars. We also demonstrate the potential of this synthetic lectin as a highly sensitive glucose sensor in aqueous solutions.
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Glycopolymer-Wrapped Carbon Nanotubes Show Distinct Interaction of Carbohydrates With Lectins
Glyconanomaterials with unique nanoscale property and carbohydrate functionality show vast potential in biological and biomedical applications. We investigated the interactions of noncovalent complexes of single-wall carbon nanotubes that are wrapped by disaccharide lactose-containing glycopolymers with the specific carbohydrate-binding proteins. The terminal galactose (Gal) of glycopolymers binds to the specific lectin as expected. Interestingly, an increased aggregation of nanotubes was also observed when interacting with a glucose (Glc) specific lectin, likely due to the removal of Glc groups from the surface of nanotubes resulting from the potential binding of the lectin to the Glc in the glycopolymers. This result indicates that the wrapping conformation of glycopolymers on the surface of nanotubes potentially allows improved accessibility of the Glc for specific lectins. Furthermore, it shows that the interaction between Glc groups in the glycopolymers and nanotubes play a key role in stabilizing the nanocomplexes. Overall, our results demonstrate that nanostructures can enable conformation-dependent interactions of glycopolymers and proteins and can potentially lead to the creation of versatile optical sensors for detecting carbohydrate-protein interactions with enhanced specificity and sensitivity.
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- Award ID(s):
- 1917513
- PAR ID:
- 10335254
- Date Published:
- Journal Name:
- Frontiers in Chemistry
- Volume:
- 10
- ISSN:
- 2296-2646
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3389/fchem.2022.852988
