Biomimetic Glycosylated Polythreonines by N-Carboxyanhydride Polymerization

Glycosylated threonine (Thr) is a structural motif found in seemingly disparate natural proteins from deep-sea collagen to mucins. Synthetic mimics of these important proteins are of great interest in biomedicine. Such materials also provide ready access to probe the contributions of individual amino acids to protein structure in a controlled and tunable manner. N-Carboxyanhydride (NCA) polymerization is one major route to such biomimetic polypeptides. However, challenges in the preparation and polymerization of Thr NCAs have impeded obtaining such structures. Here, we present optimized routes to several glycosylated and acetylated Thr NCAs of high analytical purity. Transition metal catalysis produced tunable homo-, statistical, and block-polypeptides with predictable chain lengths and low dispersities. We conducted structural work to examine their aqueous conformations and found that a high content of free OH Thr induces the formation of water-insoluble beta-sheets. However, glycosylation appears to induce a polyproline II-type helical conformation, which sheds light on the role of glyco-Thr in rigid proteins such as mucins and collagen.

Automated summary

This article introduces the importance of glycosylated threonine and its synthesis methods. Through high purity threonine polymers, the contributions of individual amino acids to protein structure can be explored. Structural studies have found that glycosylated threonine can induce the formation of specific conformations, shedding light on the function of rigid proteins such as mucins and collagen.