![]() In the case of sialic acid binding viruses, NA also facilitates the release of progeny virions from infected cells. Therefore inhibition of NA can hinder the spread of sialic acid binding pathogens, and NA inhibitors offer great potential as anti-microbial agents. By destroying sialic acid-containing glycosides, NA facilitates the movement of pathogens through biological environments rich in sialic acid receptors, including mammalian tissues and mucus. NA is found in many types of pathogens including Trypanosoma cruzi, Clostridium perfringens, Streptococcus pneumoniae, Vibrio cholerae, mumps virus, parainfluenza virus and influenza virus. Common substrates recognized by NA contain terminal N-acetylneuraminic acid (Neu5Ac, NANA) or N-glycolylneuraminic acid (Neu5Gc, NGNA) with an α2-3 or α2-6 ketosidic bond to galactose. ![]() Neuraminidase (NA, EC 3.2.1.18), also referred to as sialidase, is a retaining glycosidase that hydrolyzes α-ketosidic linkages to sialic acids. These results confirm that this novel anomeric sulfo modification offers great potential to improve the potency of next-generation NA inhibitors including covalent inhibitors. The sulfo-sialic acid analogues described in this report are also more potent inhibitors of influenza NA (up to 40-fold) and bacterial NA (up to 8.5-fold) relative to the corresponding anomeric phosphonic acids. While 2-decarboxy-2-deoxy-2-sulfo- N-acetylneuraminic acid contains no further modifications of the 2-deoxy-pyranose ring, it is still a more potent inhibitor of avian-origin H5N1 neuraminidase (NA) and drug-resistant His275Tyr NA as compared to the oxocarbenium ion transition state analogue 2,3-dehydro-2-deoxy- N-acetylneuraminic acid. These novel compounds, which we refer to as sulfo-sialic acid analogues, include 2-decarboxy-2-deoxy-2-sulfo- N-acetylneuraminic acid and its 4-deoxy-3,4-dehydrogenated pseudoglycal. ![]() The design, synthesis and application of N-acetylneuraminic acid-derived compounds bearing anomeric sulfo functional groups are described. ![]()
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |