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Glycopeptide Self-Assembly Modulated by Glycan Stereochemistry through Glycan–Aromatic Interactions

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journal contribution
posted on 25.09.2020, 08:35 by Changdong He, Shuang Wu, Dangliang Liu, Changbiao Chi, Weilin Zhang, Ming Ma, Luhua Lai, Suwei Dong
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.