Glycopeptide Self-Assembly Modulated by Glycan Stereochemistry through Glycan-Aromatic Interactions.
Changdong HeShuang WuDangliang LiuChangbiao ChiWeilin ZhangMing MaLuhua LaiSuwei DongPublished in: Journal of the American Chemical Society (2020)
Carbohydrates are often utilized to provide hydrophilicity and hydroxyl-based hydrogen bonds in self-assembling glycopeptides, affording versatile scaffolds with wide applicability in biomedical research. However, how stereochemistry of carbohydrates impacts the self-assembly process remains unclear. Here we have established a dimeric tyrosine-rich glycopeptide system for probing the corresponding hydrogelating behavior under the influence of site- and stereospecific glycosylations. Comparison of 18 glycoforms bearing monosaccharides at Tyr4 and Tyr4' shows that the glycopeptides with either α- or β-anomers exhibit contrary gelating abilities, when the glycan moieties contain axial hydroxyl groups. A high-resolution X-ray crystallographic structure of the β-galactose-containing gelator, along with other results from spectroscopic, microscopic, and rheological experiments, indicate an unusual carbohydrate-aromatic CH-π bonding that promotes glycopeptide self-assembly. These mechanistic findings, particularly evidence obtained at the angstrom scale, illuminate an unconventional role that carbohydrates can play in building supramolecules. Potential biomaterials exploiting the CH-π bond-based stabilization, as exemplified by an enzyme-resistant hydrogel, may thus be developed.
Keyphrases
- high resolution
- tissue engineering
- cell surface
- room temperature
- amino acid
- molecular docking
- drug delivery
- mass spectrometry
- single molecule
- molecular dynamics simulations
- human health
- magnetic resonance imaging
- computed tomography
- magnetic resonance
- hyaluronic acid
- wound healing
- climate change
- transition metal
- high speed