Chemical glycosylation of peptides
Whereas recombinant synthesis of glycosylated peptides and proteins yields heterogeneous products, homogeneous glycoforms with potential for better defined bioactivity can be obtained by complex chemical methods. A new technology permits straightforward selective glycosylation via incorporation of amino acid building blocks bearing glycans during the course of SPPS and LPPS. A proprietary library of highly purified and well characterized glycan derivatives of amino acids is now commercially available to support development of peptides and proteins with enhanced physicochemical and pharmacological properties.
Glycosylation involves covalent attachment of carbohydrates to macromolecules such as lipids, proteins, and peptides. Glycosylated products can be classified into five major classes namely, N-linked glycans (has carbohydrate part attached to nitrogen of asparagine or arginine side-chains), O-linked glycans (attached via the hydroxyl oxygen of serine, threonine, tyrosine, hydroxylysine, or hydroxyproline side-chains, or to oxygens on lipids such as ceramide), Phospho-glycans (linked through the phosphate group of a phospho-serine), C-linked glycans (where a sugar is added to a carbon on a tryptophan side-chain) and Glypiation (formed by the addition of a glycosylphosphatidylinositol, GPI, anchor that links proteins to lipids through glycan linkages). A number of proteins are not stable unless they contain oligosaccharides linked at the amide nitrogen of asparagine. It has been estimated that as much as 50% of all proteins are glycosylated. The influence of glycosylation on the folding and stability of glycoprotein is twofold. Firstly, the highly soluble glycans may have a direct physicochemical stabilization effect. Secondly, N-linked glyca ...