NAG-thiazoline, an N-acetyl-β-hexosaminidase inhibitor that implicates acetamido participation

Journal of the American Chemical Society

Volumn 118, Issue 28, 1996, Pages 6804-6805

  Knapp, Spencer ^a   Vocadlo, David ^b   Gao, Zhinong ^a   Kirk, Brian ^a   Lou, Jianping ^a   Withers, Stephen G ^b  

^a RUTGERS UNIVERSITY   (United States)

^b UNIVERSITY OF BRITISH COLUMBIA   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

BETA N ACETYLHEXOSAMINIDASE; THIAZOLE DERIVATIVE;

ARTICLE; ENZYME BINDING; ENZYME INHIBITION;

EID: 0029947945     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja960826u     Document Type: Article

References (31)

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4. The contribution of the acetamido group to NAGase binding has been estimated at 4.2 kcal/mol. Lai, E. C. K.; Withers, S. G. Biochemistry 1994, 33, 14743-14749.
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6. 2-Acetamido-2-deoxy-D-gluconolactone: (a) Conchie, J.; Hay, A. J.; Strachan, I.; Levvy, G. A. Biochem. J. 1967, 102, 929-941. (b) Li, S. C.; Li, Y. T. J. Biol. Chem. 1970, 245, 5153-5160. (c) Sandhoff, K.; Wassle, W. Hoppe-Seyler's Z. Physiol. Chem. 1971, 352, 1119-1133. (d) Villar, E.; Cabezas, J. E.; Calvo, P. Biochimie 1984, 66, 291-304. (e) Horsch, M.; Hoesch, L.; Fleet, G. W.; Rast, D. M. J. Enzyme Inhib. 1993, 7, 47-55.
7. 2-Acetamido-2-deoxy-D-gluconolactone: (a) Conchie, J.; Hay, A. J.; Strachan, I.; Levvy, G. A. Biochem. J. 1967, 102, 929-941. (b) Li, S. C.; Li, Y. T. J. Biol. Chem. 1970, 245, 5153-5160. (c) Sandhoff, K.; Wassle, W. Hoppe-Seyler's Z. Physiol. Chem. 1971, 352, 1119-1133. (d) Villar, E.; Cabezas, J. E.; Calvo, P. Biochimie 1984, 66, 291-304. (e) Horsch, M.; Hoesch, L.; Fleet, G. W.; Rast, D. M. J. Enzyme Inhib. 1993, 7, 47-55.
8. 2-Acetamido-2-deoxy-D-gluconolactone: (a) Conchie, J.; Hay, A. J.; Strachan, I.; Levvy, G. A. Biochem. J. 1967, 102, 929-941. (b) Li, S. C.; Li, Y. T. J. Biol. Chem. 1970, 245, 5153-5160. (c) Sandhoff, K.; Wassle, W. Hoppe-Seyler's Z. Physiol. Chem. 1971, 352, 1119-1133. (d) Villar, E.; Cabezas, J. E.; Calvo, P. Biochimie 1984, 66, 291-304. (e) Horsch, M.; Hoesch, L.; Fleet, G. W.; Rast, D. M. J. Enzyme Inhib. 1993, 7, 47-55.
9. 2-Acetamido-2-deoxy-D-gluconolactone: (a) Conchie, J.; Hay, A. J.; Strachan, I.; Levvy, G. A. Biochem. J. 1967, 102, 929-941. (b) Li, S. C.; Li, Y. T. J. Biol. Chem. 1970, 245, 5153-5160. (c) Sandhoff, K.; Wassle, W. Hoppe-Seyler's Z. Physiol. Chem. 1971, 352, 1119-1133. (d) Villar, E.; Cabezas, J. E.; Calvo, P. Biochimie 1984, 66, 291-304. (e) Horsch, M.; Hoesch, L.; Fleet, G. W.; Rast, D. M. J. Enzyme Inhib. 1993, 7, 47-55.
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11. 2-Acetamido-(2-deoxy and 1,2-dideoxy)nojirimycin: (a) Kappes, E.; Legler, G. J, Carbohydr. Chem. 1989, 8, 371-388. (b) Kajimoto, T.; Liu, K. K.-C.; Pederson, R. L.; Zhong, Z.; Ichikawa, Y.; Porco, J. A.; Wong, C-H. J. Am. Chem. Soc. 1991, 113, 6187-6196. (c) Legler, G.; Lullau, E.; Kappes, E.; Kastenholz, F. Biochim. Biophys. Acta 1991,1080, 89-95. (d) Fleet, G. W. J.; Smith, P. W.; Nash, R. J.; Fellows, L. E.; Parekh, R. B.; Rademacher, T. W. Chem. Lett. 1986, 1051-1054.
12. 2-Acetamido-(2-deoxy and 1,2-dideoxy)nojirimycin: (a) Kappes, E.; Legler, G. J, Carbohydr. Chem. 1989, 8, 371-388. (b) Kajimoto, T.; Liu, K. K.-C.; Pederson, R. L.; Zhong, Z.; Ichikawa, Y.; Porco, J. A.; Wong, C-H. J. Am. Chem. Soc. 1991, 113, 6187-6196. (c) Legler, G.; Lullau, E.; Kappes, E.; Kastenholz, F. Biochim. Biophys. Acta 1991,1080, 89-95. (d) Fleet, G. W. J.; Smith, P. W.; Nash, R. J.; Fellows, L. E.; Parekh, R. B.; Rademacher, T. W. Chem. Lett. 1986, 1051-1054.
13. 2-Acetamido-(2-deoxy and 1,2-dideoxy)nojirimycin: (a) Kappes, E.; Legler, G. J, Carbohydr. Chem. 1989, 8, 371-388. (b) Kajimoto, T.; Liu, K. K.-C.; Pederson, R. L.; Zhong, Z.; Ichikawa, Y.; Porco, J. A.; Wong, C-H. J. Am. Chem. Soc. 1991, 113, 6187-6196. (c) Legler, G.; Lullau, E.; Kappes, E.; Kastenholz, F. Biochim. Biophys. Acta 1991,1080, 89-95. (d) Fleet, G. W. J.; Smith, P. W.; Nash, R. J.; Fellows, L. E.; Parekh, R. B.; Rademacher, T. W. Chem. Lett. 1986, 1051-1054.
14. Some recent NAGase inhibitors: (a) Heightman, T. D.; Ermert, P.; Klein, D.; Vasella, A. Helv. Chim. Acta 1995, 78, 514-532. (b) Liessem, B.; Giannis, A.; Sandhoff, K.; Nieger, M. Carbohydr. Res. 1993, 250, 19-30. (c) Wolk, D. R.; Vasella, A.; Schweikart, T.; Peter, M. G. Helv. Chim. Acta 1992, 75, 323-334. (d) Aoyagi, T.; Suda, H.; Uotani, K.; Kojima, F.; Aoyama, T.; Horiguchi, K.; Hamada, M.; Takeuchi, T. J. Antibiot. 1992, 45, 1404-1408. (e) Aoyama, T.; Naganawa, H.; Suda, H.; Uotani, K.; Aoyagi, T.; Takeuchi, T. J. Antibiot. 1992, 45, 1557-1558. (f) Horsch, M.; Hoesch, L.; Vasella, A.; Rast, D. M. Eur. J. Biochem. 1991, 197, 815-818.
15. Some recent NAGase inhibitors: (a) Heightman, T. D.; Ermert, P.; Klein, D.; Vasella, A. Helv. Chim. Acta 1995, 78, 514-532. (b) Liessem, B.; Giannis, A.; Sandhoff, K.; Nieger, M. Carbohydr. Res. 1993, 250, 19-30. (c) Wolk, D. R.; Vasella, A.; Schweikart, T.; Peter, M. G. Helv. Chim. Acta 1992, 75, 323-334. (d) Aoyagi, T.; Suda, H.; Uotani, K.; Kojima, F.; Aoyama, T.; Horiguchi, K.; Hamada, M.; Takeuchi, T. J. Antibiot. 1992, 45, 1404-1408. (e) Aoyama, T.; Naganawa, H.; Suda, H.; Uotani, K.; Aoyagi, T.; Takeuchi, T. J. Antibiot. 1992, 45, 1557-1558. (f) Horsch, M.; Hoesch, L.; Vasella, A.; Rast, D. M. Eur. J. Biochem. 1991, 197, 815-818.
16. Some recent NAGase inhibitors: (a) Heightman, T. D.; Ermert, P.; Klein, D.; Vasella, A. Helv. Chim. Acta 1995, 78, 514-532. (b) Liessem, B.; Giannis, A.; Sandhoff, K.; Nieger, M. Carbohydr. Res. 1993, 250, 19-30. (c) Wolk, D. R.; Vasella, A.; Schweikart, T.; Peter, M. G. Helv. Chim. Acta 1992, 75, 323-334. (d) Aoyagi, T.; Suda, H.; Uotani, K.; Kojima, F.; Aoyama, T.; Horiguchi, K.; Hamada, M.; Takeuchi, T. J. Antibiot. 1992, 45, 1404-1408. (e) Aoyama, T.; Naganawa, H.; Suda, H.; Uotani, K.; Aoyagi, T.; Takeuchi, T. J. Antibiot. 1992, 45, 1557-1558. (f) Horsch, M.; Hoesch, L.; Vasella, A.; Rast, D. M. Eur. J. Biochem. 1991, 197, 815-818.
17. Some recent NAGase inhibitors: (a) Heightman, T. D.; Ermert, P.; Klein, D.; Vasella, A. Helv. Chim. Acta 1995, 78, 514-532. (b) Liessem, B.; Giannis, A.; Sandhoff, K.; Nieger, M. Carbohydr. Res. 1993, 250, 19-30. (c) Wolk, D. R.; Vasella, A.; Schweikart, T.; Peter, M. G. Helv. Chim. Acta 1992, 75, 323-334. (d) Aoyagi, T.; Suda, H.; Uotani, K.; Kojima, F.; Aoyama, T.; Horiguchi, K.; Hamada, M.; Takeuchi, T. J. Antibiot. 1992, 45, 1404-1408. (e) Aoyama, T.; Naganawa, H.; Suda, H.; Uotani, K.; Aoyagi, T.; Takeuchi, T. J. Antibiot. 1992, 45, 1557-1558. (f) Horsch, M.; Hoesch, L.; Vasella, A.; Rast, D. M. Eur. J. Biochem. 1991, 197, 815-818.
18. Some recent NAGase inhibitors: (a) Heightman, T. D.; Ermert, P.; Klein, D.; Vasella, A. Helv. Chim. Acta 1995, 78, 514-532. (b) Liessem, B.; Giannis, A.; Sandhoff, K.; Nieger, M. Carbohydr. Res. 1993, 250, 19-30. (c) Wolk, D. R.; Vasella, A.; Schweikart, T.; Peter, M. G. Helv. Chim. Acta 1992, 75, 323-334. (d) Aoyagi, T.; Suda, H.; Uotani, K.; Kojima, F.; Aoyama, T.; Horiguchi, K.; Hamada, M.; Takeuchi, T. J. Antibiot. 1992, 45, 1404-1408. (e) Aoyama, T.; Naganawa, H.; Suda, H.; Uotani, K.; Aoyagi, T.; Takeuchi, T. J. Antibiot. 1992, 45, 1557-1558. (f) Horsch, M.; Hoesch, L.; Vasella, A.; Rast, D. M. Eur. J. Biochem. 1991, 197, 815-818.
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31. The time course of release of 4-methylumbelliferone from 7 by jack bean NAGase was followed by establishing a series of reaction mixtures, each containing NAGase (2.4 μg/mL) and 7 (0.65 mM) in 420 μL of 50 mM citrate buffer containing 100 mM NaCl and 0.1% BSA at pH 5.0. These mixtures were quenched at various incubation times by adding 1.26 mL of 0.2 M glycine buffer, pH 10.65. The fluorescence due to 4-methylumbelliferone was then measured at 450 nM. The resulting time-dependent decrease in activity was shown to be due to the buildup of a reversible inhibitor rather than covalent inactivation by repeating the experiment at a higher enzyme concentration and then diluting the sample prior to assay. Under these conditions essentially no time-dependent loss of enzyme activity was observed.