Sugar-assisted Ligation for Glycoprotein Synthesis

As a long-term expert in the field of the chemical synthesis of glycoprotein, Creative Biolabs owns lots of scientists who are proficient in glycoprotein synthesis using different strategies. Sugar-assisted ligation (SAL) is a useful strategy for homogeneous glycoprotein synthesis. Our scientists have accumulated rich experience in employing SAL for glycoprotein synthesis, and we are more than happy to share our experience and help our customers in glycoprotein development.

Introduction of SAL for Glycoprotein Synthesis

Fig.1 Mechanism of SAL. (Bennett, 2008)

One of the most common methods to the chemical synthesis of glycoproteins involves the ligation of smaller peptide fragments through native chemical ligation (NCL), which has proved to be extremely powerful for the convergent synthesis of large glycopeptides and glycoproteins. Although useful, NCL is limited by the requirement for a N-terminal cysteine, alanine or phenylalanine residue. Although the use of auxiliaries has expanded the number of possible ligation junctions available for glycoprotein synthesis, NCL is limited to sterically unencumbered amino acids.

Scientists have developed an alternative approach, termed SAL for glycoprotein synthesis. This method uses a glycopeptide in which the thiol auxiliary is attached through a sugar (N-acetylglucosamine or N-acetylgalactosamine) via either the C-2 acetamide or a 2-mercaptoacetate moiety on the C-3 hydroxyl group. These glycopeptides undergo thioester exchange with a peptide thioester, followed by an S to N acyl shift to afford a native peptide linkage. The reaction shows high tolerance at the ligation junction and is orthogonal to functional groups present in all proteinogenic amino acids. After ligation, the thiol handle can be removed through hydrogenolysis or deacetylation. However, there is a problem that the use of chemical desulfurization is incompatible with unprotected cysteine residues. It is exciting that this problem is solved by the protection of cysteine residues with an acetamidomethyl protecting group. SAL has been employed for the synthesis of glycoprotein antibiotic diptericin, which opens new avenues for the synthesis of complex glycopeptides and homogeneous glycoproteins.

SAL for Glycoprotein Synthesis at Creative Biolabs

SAL is a useful method for the convergent synthesis of glycoprotein. This approach can be carried out not only the thiol auxiliary is attached to a monosaccharide but also the thiol auxiliary is attached to complex glycans, which are frequently observed in nature. A disadvantage of SAL is the need to desulfurize the thiol handle to regenerate the native carbohydrate N-acetyl group as this is not compatible with any side-chain thiols of cysteine residues that may be present in the target sequence. In terms of the extensive experience in the development of glycoprotein, Creative Biolabs has perfected our technical pipelines of glycoprotein synthesis. We circumvent this disadvantage by introducing a thiol side chain in a base-labile O-3-thioacetate in the sugar that mediates ligation.

Powered by our advanced synthesis platforms and experienced technical personnel, Creative Biolabs is fully competent and dedicated to serving as your one-stop-shop for glycoprotein synthesis and comprehensive analysis. For more detailed information, please feel free to contact us or directly send us an inquiry.

Reference

1. Bennett, C.S.; et al. Sugar-assisted glycopeptide ligation with complex oligosaccharides: scope and limitations. Journal of the American Chemical Society. 2008, 130(36): 11945-52.

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