Expanding the Conformational Landscape of Minimalistic Tripeptides by Their O-Glycosylation

• DOI: 10.1021/jacs.1c07592
• Publication Date: 2021-11-19T13:33:20Z
• Authors: Alexandra Brito; Dhwanit Dave; Ayala Lampel; Vânia I. B. Castro; Daniela Kroiss; Rui L. Reis; Tell Tuttle; Rein V. Ulijn; Ricardo A. Pires; Iva Pashkuleva
• Keywords: 0301 basic medicine; Science & Technology; Glycosylation; Reductionist approach; Protein Conformation; GLYCOSYLATION; Self-assembly; Molecular Dynamics Simulation; 540; CH-pi interactions; Chemistry; Aggregation; 03 medical and health sciences; QD; Protein Multimerization; Oligopeptides; Glycoproteins

We report on the supramolecular self-assembly of tripeptides and their O-glycosylated analogues, in which the carbohydrate moiety is coupled to a central serine or threonine flanked by phenylalanine residues. The substitution of serine with threonine introduces differential side-chain interactions, which results in the formation of aggregates with different morphology. O-glycosylation decreases the aggregation propensity because of rebalancing of the π interactions. The glycopeptides form aggregates with reduced stiffness but increased thermal stability. Our results demonstrate that the designed minimalistic glycopeptides retain critical functional features of glycoproteins and therefore are promising tools for elucidation of molecular mechanisms involved in the glycoprotein interactome. They can also serve as an inspiration for the design of functional glycopeptide-based biomaterials.