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We report a turn-on tetravalent sialic acid-coated tetraphenylethene luminogen (TPE4S) with excellent hydrophilicity, good stability, high sensitivity and unique selectivity towards sialidases, and the maximum fluorescence enhancement was ∼40 fold. More importantly, TPE4S was successfully utilized for the screening of sialidase inhibitors and diagnosis of bacterial vaginosis.

Adenovirus type 37 (Ad37) is one of the principal agents responsible for epidemic keratoconjunctivitis (EKC), a severe ocular infection that remains without any available treatment. Recently, a trivalent sialic acid derivative (ME0322, Angew. Chem. Int. Ed., 2011, 50, 6519) was shown to function as a highly potent inhibitor of Ad37, efficiently preventing the attachment of the virion to the host cells and subsequent infection. Here, new trivalent sialic acid derivatives were designed, synthesized and their inhibitory properties against Ad37 infection of the human corneal epithelial cells were investigated. In comparison to ME0322, the best compound (17a) was found to be over three orders of magnitude more potent in a cell-attachment assay (IC50 = 1.4 nM) and about 140 times more potent in a cell-infection assay (IC50 = 2.9 nM). X-ray crystallographic analysis demonstrated a trivalent binding mode of all compounds to the Ad37 fiber knob. For the most potent compound ophthalmic toxicity in rabbits was investigated and it was concluded that repeated eye administration did not cause any adverse effects.

Novel 3-C-alkylated-Neu5Ac2en derivatives have been designed to target the expanded active site cavity of influenza virus sialidases with an open 150-loop, currently seen in X-ray crystal structures of influenza A virus group-1 (N1, N4, N5, N8), but not group-2 (N2, N9), sialidases. The compounds show selectivity for inhibition of H5N1 and pdm09 H1N1 sialidases over an N2 sialidase, providing evidence of the relative 150-loop flexibility of these sialidases. In a complex with N8 sialidase, the C3 substituent of 3-phenylally-Neu5Ac2en occupies the 150-cavity while the central ring and the remaining substituents bind the active site as seen for the unsubstituted template. This new class of inhibitors, which can 'trap' the open 150-loop form of the sialidase, should prove useful as probes of 150-loop flexibility.

A cytidine 5'-monophosphate (CMP)-sialic acid analogue carrying a fluorescent reporter group, an inhibitor of sialyltransferase, was synthesised in order to investigate glycan synthesis events in cells. The compound was found to be a substrate of a CMP-sialic acid transporter, and specific Golgi vesicles were visualised in the cells.

An efficient short protocol for the preparation of N-perfluoroacylated glycals of neuraminic acid, by simple short treatment of differently protected N-acetylneuraminic acid with perfluorinated anhydrides in acetonitrile at 135 degrees C, is reported, together with a rationalitazion of the reaction that allows the alternative formation of N-perfluoroacylated 1,7-lactones to be previewed under the same reaction conditions.

Sialic acid is the terminal sugar found on most glycoproteins and is crucial in determining serum half-life and immunogenicity of glycoproteins. Sialic acid analogs are antiviral therapeutics as well as crucial tools in bacterial pathogenesis research, immunobiology and development of cancer diagnostic imaging. The scarce supply of sialic acid hinders production of these materials. We have developed an efficient, rapid and cost effective fermentation route to access sialic acid. Our approach uses low cost feedstock, produces an industrially relevant amount of sialic acid and is scalable to manufacturing levels. We have also shown that precursor directed biosynthesis can be used to produce a N-acyl sialic acid analog. This work demonstrates the feasibility of engineering manufacturing-friendly bacteria to produce complex, unavailable small molecules.

2-(Perfluorohexyl)ethoxymethyl chloride was prepared as a novel fluorous protecting reagent. Neu5Ac aldolase-catalyzed chemoenzymatic transformation of N-acetyl-D-mannosamine to Neu5Ac derivatives was achieved successfully by using the fluorous reagent not only for hydroxy group protection but also for fluorous tagging. This chemoenzymatic method was applied to the synthesis of 2-deoxy-2,3-didehydrosialic acid 1 known as a potent sialidase inhibitor.