New ganglioside analogs that inhibit influenze virus sialidase |
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Authors: | Yasuo Suzuki Katsuhiko Sato Makoto Kiso Akira Hasegawa |
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Institution: | (1) Department of Biochemistry, University of Shizuoka, School of Pharmaceutical Science, 395 Yada, 422 Shizuoka, Japan;(2) Department of Applied Bio-organic Chemistry, Gifu University, 501-11 Gifu, Japan |
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Abstract: | Synthetic thioglycoside-analogs of gangliosides such as Neu5Ac)2-S-6)Glc-(1-1)Ceramide (1) and the GM3 analog Neu5Ac(2-S-6)Gal-(1–4)Glc(1-1)Ceramide (2), competitively inhibited GM3 hydrolysis by the sialidase of different subtypes of human and animal influenza viruses with an apparent Ki value of 2.8×10–6 and 1.5×10–5 M, respectively. The inhibitory activity of the ganglioside GM4 analog Neu5Ac-(2-S-6)Gal-(1-1)Ceramide (3)], in which the glucose of 1 was substituted by galactose, was lower than that of 1 (Ki =1.0×10–4 M). The thioglycoside-analogs (1, 2, 3) of the gangliosides were nonhydrolyzable substrates for influenza virus sialidase. The inhibitory activity of 1 to bacterial sialidases fromClostridium perfringens andArthrobacter ureafaciens was considerably lower than that to influenza virus sialidase, indicating that the structure of the active site in bacterial and influenza virus sialidase may be different and the analogs may be useful to determine the orientation of the substrate to the active site of sialidases, especially of influenza viruses.Abbreviations Cer
ceramide
- GM3
Neu5Ac(2–3)Gal(1–4)Glc(1-1)Cer
- GM4
Neu5Ac(2–3)Gal(1-1)Cer
Gangliosides were abbreviated according to Svennerholm 1] and the recommendation of the IUPAC-IUB Commission on Biochemical Nomenclature 2]. |
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Keywords: | sialidase inhibitor Thioglycoside-analog of ganglioside influenza virus |
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