Sialosides libraries

In order to prepare o2,6-linked sialoside libraries with naturally occurring and non-natural sialic acid modifications, a flexible o2,6-sialyltransferase enzyme is required. Although several manunalian sialyltransferases have been reported to have relatively broad donor substrate specificity (for example, rat liver o2,6-sialyltransferases can tolerate a variety of modifications on the Neu5Ac moiety of CMP-Neu5Ac) (29-32), but they suffer from low expression level which limits their applications in preparative- and large- scale synthesis of sialosides. 

Seven different bacterial sialidases, including six commercially available sialidases from Arthrobacter ureafaciens, Clostridium perfingens. Streptococcus sp. IID, Vibrio cholera. Salmonella typhimurium, and Streptococcus pneumoniae, as well as PmSTl which also possesses sialidase activity (20), were used as model systems to test the application of the sialoside library and the 96-well plate based high-throughput colorimetric screening method. 

Scheme 6. One-pot three-enzyme chemoenzymatic synthesis of pNP-tagged o2,3- and a2,6-linked sialoside libraries containing a list of naturally occurring sialic acidforms.

A versatile synthesis of a sialoside library was established using three enzymes,... 

Chokhawala, H. A., Yu, H., and Chen, X., High-throughput substrate specificity studies of sialidases by using chemoenzymatically synthesized sialoside libraries. ChemBioChem... 

Similarly, standard drug DANA was docked for NEU3 enzyme, which revealed about the presence of big hydrophobic pocket near the C9 position of the sialic acid. Therefore, a library of mammalian NEU3 enzyme inhibitors was synthesized by modifying DANA at C9 and N5Ac positions using click reaction. AT-5-Azidoacetyl- and 9-azido-9-deoxy DANA derivatives were synthesized from NeuSAc, which was clicked with different alkyne-functionalized molecules to afford diverse triazolo-sialosides 80 (20 10 pM), hexyl 81 (23 4pM), and phenoxymethyl 82 (45 3 pM) (Figure 6.5). 

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