Glycopolypeptides: Synthesis, Self-assembly and Biomedical Applications

Glycopolypeptides are a kind of biodegradable polymers consisting of polypeptides (polyamino acid) and carbohydrates (such as monosaccharide, oligosaccharides and polysaccharides). Owing to their chemical similarity to glycoproteins, glycopolypeptides can, to some extent, mimic the structure and function of natural glycoproteins, and have attracted broad attention recently. Two general strategies have been developed for the synthesis of glycopolypeptides, i.e. direct polymerization of glycosylated monomers and post-polymerization glycosylation of reactive polypeptides. Although the synthesis of glycopolypeptides can be traced back to sixty years ago, the synthesis of glycopolypeptides with Control architectures and high molecular weights can be achieved when high purified sugar-substituted amino acid N-carboxyanhydride (NCA) monomers for Control ring-opening polymerization and "clickable" polypeptides for "click" glycosylation have been extensively developed. Based on these advances on Control synthesis of glycopolypeptides, many efforts are devoted to studying the self-assembly of amphiphilic glycopolypeptide (co) polymers into various nano-structures, such as micelles, vesicles and nanorods. More interestingly, hierarchical self-assembly of an alternating amphiphilic glycopolypeptide to mimic the complex structure of natural glycoconjugates also has been achieved. In addition, as a kind of structural mimics of natural glycoproteins, the synthetic glycopolypeptides are capable of binding selectively to various carbohydrate-binding proteins, such as lectins. And the lectin-binding ability is confirmed to be dependent on the type, composition, density and distribution pattern of the sugar residues on the polypeptide backbone. Also, due to the presence of carbohydrate-binding proteins on cell surfaces, especially on the surface of cancer cells, glycopolypeptides have been widely investigated as biocompatible nanocarrieres for targeted drug/gene delivery. Most recently, glycopolypeptides-based hydrogels are receiving increasing attention for tissue engineering applications because of their ability to enhance cell adhesion and proliferation in 3D cell culture. In this article, we summarize recent advances in the synthesis and self-assembly of glycopolypeptides, and their applications in biomedical fields, such as biomolecular recognitions, targeted gene/drug delivery and scaffolds for tissue engineering, are also emphatically reviewed and discussed.