Indiscriminate Convergent Synthesis
The Introduction and Necessity for Glycoproteins Synthesis
The glycoproteins are ubiquitous in the world and the structure of glycoproteins on the surface of cells is necessary to understanding multiple complex biological processes. In this case, the synthesis of glycoproteins is essential. In general, there are two strategies for the synthesis of glycoproteins. The first option is to form putative glycan-protein linkages early to form glycopeptide building blocks that can be assembled later. The second option is to construct the link in the late synthesis stage once the protein scaffold for its presentation is in place.
Since protection requirements and possible instability need to be considered when using glycosylation building blocks, the second option is often more attractive. However, the convergent glycosylation of oligopeptides is always limited by a lack of chemistry and/or regioselectivity. What’s more, the convergent protein glycosylation methods can be further divided into chemoselective, site-specific, as well as site-selective.
IME for Indiscriminate Convergent Synthesis
IME involves the conversion of the nitrile in the cyanoethyl thioglycoside to the methyl imidate group after exposure to sodium methoxide or methanol HCl. The IME-thioglycosides can react with simple amines and protein scaffolds easily. Using different IMEs, galactosylation or mannosylation can be accomplished. Based on IME, an in vivo bipartite drug delivery system called LEAPT has been developed. Now reductive amination has been used for the modification of albumin with the reducing terminus of lactose. Squaric acid diesters can also be served as coupling reagents for amines with low molecular weight.
Dielss-Alder Chemistry for Indiscriminate Convergent Synthesis
Under mild conditions, the Dielss-Alder chemistry has been used to modify glycosylated human serum albumin (HSA) with a series of glycosides to incorporate a conjugated diene. This method has been used to conjugate capsular polysaccharide fragments of the Gram-negative bacterium Neisseria meningitides to HSA. What’s more, the indiscriminate glycosylation has been reported through an aminooxy-thiol heterobifunctional linker based upon observations of Bertozzi. Other linkers have also been employed for the antibodies discovery against synthetic glycosylphosphatidylinositol (GPI) anchors.
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