at Peking University School of Pharmaceutical Sciences
​​​​the dong research group
11. Glycopeptide Self-Assembly Modulated by Glycan Stereochemistry through Glycan−Aromatic Interactions
J. Am. Chem. Soc. 2020, 142, 40, 17015–17023
Changdong He, Shuang Wu, Dangliang Liu, Changbiao Chi, Weilin Zhang, Ming Ma, Luhua Lai, and 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.