Abstract:
Benzyl 3-deoxy-4-S-(β-D-galactopyranosyl)-4-thio-β-D-threopentopyranoside (3) is a potent inhibitor of the β-galactosidase from Escherichia coli synthesized in our laboratory. The 2′,3′,4′,6′-tetra-O-acetyl derivative of this thiodisaccharide was oxidized with m-chloroperoxybenzoic acid to give a 2:1 diastereomeric mixture of sulfoxides 2S and 2R. The absolute configurations of their sulfur stereocenters were determined by using NMR techniques and by taking into account the anisotropic effects of the S=O group in the major conformers. O-Deacetylation of 2S and 2R afforded the free thiodisaccharide S-oxides 4S and 4R, which were evaluated as inhibitors of the above-mentioned enzyme. The kinetic studies showed that 4S and 4R are competitive inhibitors of the enzyme with Ki values of 0.19 and 0.45 mM, respectively. Further enzymatic reactions demonstrated that 4S is also a substrate of the β-galactosidase, as it was diastereoselectively hydrolyzed, with 4R remaining unchanged under the same conditions. © 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Registro:
Documento: |
Artículo
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Título: | Thiodisaccharide sulfoxides: Absolute configuration of the so sulfur atom and influence on the biological activity towards the β-galactosidase from E. coli |
Autor: | Colomer, J.P.; Mayordomo, M.Á.C.; De Toro, B.F.; Jiménez-Barbero, J.; Varela, O. |
Filiación: | CIHIDECAR-CONICET-UBA, Depto. Química Orgánica, Universidad de Buenos Aires, Ciudad Universitaria, Pab. II, Buenos Aires, 1428, Argentina Depto. Química Orgánica i, Facultad Ciencias Químicas, Universidad Complutense de Madrid, Avd. Complutense s/n, Madrid, 28040, Spain Department of Chemical and Physical Biology, Centro de Investigaciones Biológicas, CSIC, Ramiro Maeztu 9, Madrid, 28040, Spain Structural Biology Unit, CIC BioGUNE, Parque Tecnológico de Bizkaia Building 801A, Derio, 48160, Spain IKERBASQUE, Basque Foundation for Science, Bilbao, 48011, Spain
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Palabras clave: | Biomimetics; Carbohydrates; Configuration determination; Enzymes; Inhibitors; Sulfoxides |
Año: | 2015
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Volumen: | 2015
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Número: | 7
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Página de inicio: | 1448
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Página de fin: | 1455
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DOI: |
http://dx.doi.org/10.1002/ejoc.201403609 |
Título revista: | European Journal of Organic Chemistry
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Título revista abreviado: | Eur. J. Org. Chem.
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ISSN: | 1434193X
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CODEN: | EJOCF
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Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_1434193X_v2015_n7_p1448_Colomer |
Referencias:
- Driguez, H., (2001) ChemBioChem, 2, pp. 311-318
- Driguez, H., (1997) Top. Curr. Chem., 187, pp. 85-116
- Witczak, Z.J., (1999) Curr. Med. Chem., 6, pp. 159-172
- Witczak, Z.J., Culhane, J.M., (2005) Appl. Microbiol. Biotechnol., 69, pp. 237-244
- Witczak, Z.J., (2013) Phosphorus Sulfur Silicon Relat. Elem., 188, pp. 413-417
- Wen, X., Yuan, Y., Kuntz, D.A., Rose, D.R., Pinto, B.M., (2005) Biochemistry, 44, pp. 6729-6737
- Wormald, M.R., Petrescu, A.J., Pao, Y.-L., Glithero, A., Elliott, T., Dwek, R.A., (2002) Chem. Rev., 102, pp. 371-386
- Ritchie, G.E., Moffatt, B.E., Sim, R.B., Morgan, B.P., Dwek, R.A., Rudd, P.M., (2002) Chem. Rev., 102, pp. 305-319
- Yuasa, H., Saotome, C., Kanie, O., (2002) Trends Glycosci. Glycotechnol., 14, pp. 231-254
- Repetto, E., Marino, C., Varela, O., (2013) Bioorg. Med. Chem., 21, pp. 3327-3333
- Manzano, V.E., Uhrig, M.L., Varela, O., (2012) Org. Biomol. Chem., 10, pp. 8884-8894
- Cagnoni, A.J., Varela, O., Gouin, S.G., Kovensky, J., Uhrig, M.L., (2011) J. Org. Chem., 76, pp. 3064-3077
- Khiar, N., Fernández, I., Araújo, C.S., Rodríguez, J.-A., Suárez, B., Álvarez, E., (2003) J. Org. Chem., 68, pp. 1433-1442
- Witczak, Z.J., Kaplon, P., Dey, P.M., (2003) Carbohydr. Res., 338, pp. 11-18
- Sanhueza, C.A., Arias, A.C., Dorta, R.L., Vázquez, J.T., (2010) Tetrahedron: Asymmetry, 21, pp. 1830-1832
- Sanhueza, C.A., Dorta, R.L., Vázquez, J.T., (2011) J. Org. Chem., 76, pp. 7769-7780
- Sanhueza, C.A., Dorta, R.L., Vázquez, J.T., (2013) Tetrahedron: Asymmetry, 24, pp. 582-593
- Tarozzi, A., Angeloni, C., Malaguti, M., Morroni, F., Hrelia, S., Hrelia, P., (2013) Oxid. Med. Cell Longev., p. 415078
- Li, J., Zhao, J., Hamer-Maansson, J.E., Andersson, T., Fulmer, R., Illueca, M., Lundborg, P., (2006) Clin. Ther., 28, pp. 419-427
- Darwish, M., Kirby, M., Hellriegel, E.T., Robertson, P., Jr., (2009) Clin. Drug Invest., 29, pp. 613-623
- Khiar, N., Alonso, I., Rodriguez, N., Fernandez-Mayoralas, A., Jiménez-Barbero, J., Nieto, O., Cano, F., Martin-Lomas, M., (1997) Tetrahedron Lett., 38, pp. 8267-8270
- Karthaus, O., Shoda, S., Kobayashi, S., (1994) Tetrahedron: Asymmetry, 5, pp. 2213-2216
- Showalterk, H.D.H., Winters, R.T., Sercel, A.D., Michel, A., (1991) Tetrahedron Lett., 32, pp. 2849-2852
- Colomer, J.P., Manzano, V.E., Varela, O., (2013) Eur. J. Org. Chem., pp. 7343-7353
- Cagnoni, A.J., Uhrig, M.L., Varela, O., (2009) Bioorg. Med. Chem., 17, pp. 6203-6212
- Fernández, I., Khiar, N., (2003) Chem. Rev., 103, pp. 3651-3705
- Calle, L., Roldós, V., Cañada, F.J., Uhrig, M.L., Cagnoni, A.J., Manzano, V.E., Varela, O., Jiménez-Barbero, J., (2013) Chem. Eur. J., 19, pp. 4262-4270
- Green, C.H., Hellier, D.G., (1972) J. Chem. Soc. Perkin Trans., 2, pp. 458-463
- Richard, J.P., (1998) Biochemistry, 37, pp. 4305-4309
- Sinnot, M.L., (1990) Chem. Rev., 90, pp. 1171-1202
- Griesser, H.W., Muller-Hill, B., Overath, P., (1983) Eur. J. Biochem., 137, pp. 567-572
- Matthews, B.W., (2005) C. R. Biol., 328, pp. 549-556
- Heightman, T.D., Vasella, A.T., (1999) Angew. Chem. Int. Ed., 38, pp. 750-770
- (1999) Angew. Chem., 111, p. 794
Citas:
---------- APA ----------
Colomer, J.P., Mayordomo, M.Á.C., De Toro, B.F., Jiménez-Barbero, J. & Varela, O.
(2015)
. Thiodisaccharide sulfoxides: Absolute configuration of the so sulfur atom and influence on the biological activity towards the β-galactosidase from E. coli. European Journal of Organic Chemistry, 2015(7), 1448-1455.
http://dx.doi.org/10.1002/ejoc.201403609---------- CHICAGO ----------
Colomer, J.P., Mayordomo, M.Á.C., De Toro, B.F., Jiménez-Barbero, J., Varela, O.
"Thiodisaccharide sulfoxides: Absolute configuration of the so sulfur atom and influence on the biological activity towards the β-galactosidase from E. coli"
. European Journal of Organic Chemistry 2015, no. 7
(2015) : 1448-1455.
http://dx.doi.org/10.1002/ejoc.201403609---------- MLA ----------
Colomer, J.P., Mayordomo, M.Á.C., De Toro, B.F., Jiménez-Barbero, J., Varela, O.
"Thiodisaccharide sulfoxides: Absolute configuration of the so sulfur atom and influence on the biological activity towards the β-galactosidase from E. coli"
. European Journal of Organic Chemistry, vol. 2015, no. 7, 2015, pp. 1448-1455.
http://dx.doi.org/10.1002/ejoc.201403609---------- VANCOUVER ----------
Colomer, J.P., Mayordomo, M.Á.C., De Toro, B.F., Jiménez-Barbero, J., Varela, O. Thiodisaccharide sulfoxides: Absolute configuration of the so sulfur atom and influence on the biological activity towards the β-galactosidase from E. coli. Eur. J. Org. Chem. 2015;2015(7):1448-1455.
http://dx.doi.org/10.1002/ejoc.201403609