N ‐Acetylneuraminic Acid Derivatives and Mimetics as Anti‐Influenza Agents

Carbohydrate scaffolds in chemical genetic studies

“…It is now well established that the HIV infection starts with the interaction of the glycidic part of the viral glycoprotein gp120 with the CD4 receptors of T-lymphocytes (Mattews et al, 1987). Influenza viruses contain surface glycoproteins (haemagglutinin and neuraminidase) recognising the terminal neuraminic acid residue associated with glycoproteins of the upper respiratory tract and the lung in humans; this recognition is the first act of the infection which occurs by cleavage of the neuraminic acid residue performed by the neuraminidase (Thomson and von Itzstein, 2003). Protein glycosylation is also responsible for conformational changes that modify the behaviour of the macromolecule.…”

A 1H STD NMR spectroscopic investigation of sialylnucleoside mimetics as probes of CMP-Kdn synthetase

“…We have previously shown that compounds which mimic sialic acids are useful probes in the identification of substrate or product sub-structural binding requirements of sialic acid-recognising proteins [3,25,26]. Therefore, we thought it of value to investigate such binding requirements of the nucleotide CMP-Kdn synthetase through the evaluation of selected sialylnucleoside mimetics (8a and 8b).…”

Unsaturated N-acetyl- D-glucosaminuronic acid glycosides as inhibitors of influenza virus sialidase

“…We believe that these mimetics provide an excellent opportunity for the complete replacement of the glycerol sidechain of Neu5Ac2en (3) with either functionalised or non-functionalised hydrophobic groups and to investigate the influence of such substitutions on sialidase activity. In general, we have found that while bacterial sialidases can tolerate the introduction of hydrophobic moieties, all of the synthesised mimetics, to date, are less potent inhibitors of the investigated bacterial sialidases when compared with Neu5Ac2en (3).…”

“…To date the most successful small molecule influenza virus inhibitors developed have targeted the enzymic function sialidase and these developments have been reviewed elsewhere [2][3][4][5]. Both Relenza TM (1), a carbohydrate-based drug, and Tamiflu TM (2a), a carbocyclic mimetic (a pseudocarbohydrate) are potent and clinically effective antiinfluenza drugs [6].…”

“…As a response to this threat, apart from vaccine development, a number of groups have been engaged in heightened activities towards the discovery and development of small molecule anti-influenza drugs that target the viral surface glycoproteins haemagglutinin and sialidase [2][3][4].…”