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Hashimoto, W.; Muraka, K. Biosci. Biotechnol. Biochem.
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We examined the type of inhibition of this enzyme by 5–7
and 9–11 through a Lineweaver–Burk plot of a-rhamnos-
idase kinetics, which showed that all the tested pyrroli-
dines were competitive inhibitors of a-rhamnosidase
(Fig. 4).
5. (a) Chua, J. E. H.; Manning, P. A.; Morona, R.
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Except for the inhibition of b-amylase by compound 9
that showed 46.6% inhibition at 200 lM concentration,
all synthetic pyrrolidines do not demonstrate inhibitory
activity at 200 lM against seven glycosidases16 (a-gluco-
sidase from Bakers yeast, a-mannosidase from Jack
Beans, a-amylase from Bacillus licheniformis, b-glucosi-
dase from Almonds, b-galactosidase from Escherichia
coli, b-amylase from Barley and invertase from Bakers
yeast), using this data we could state that 5–7 and
9–11 are highly selective and potent inhibitors of
a-rhamnosidase.
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9. Davis, B. G.; Brandstetter, T. W.; Hackett, L.; Winches-
ter, B. G.; Nash, R. J.; Watson, A. A.; Griffiths, R. C.;
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In conclusion, the synthesized 12 polyhydroxylated
pyrrolidines were identified with structure-based inhibi-
tory activity and specific inhibitory activity for a-rham-
nosidase. The compound
7
(2S,3S,4R)-deacetyl
anisomycin, had the best inhibitory activity because it
possesses the same stereoconfiguration at C1 and C2
as a-L-rhamnopyranoside.
11. (a) Davis, B. G.; Hull, A.; Smith, C.; Nash, R. J.;
Watshon, A. A.; Winkler, D. A.; Griffiths, R. C.; Fleet, G.
W. J. Tetrahedron: Asymmetry 1998, 9, 2947; (b) Fair-
banks, A. J.; Carpenter, N.; Fleet, G. W. J.; Ramsden, N.
G.; Cenci de Bello, I.; Winchester, B. G.; Al-Daher, S. S.;
Nagahashi, G. Tetrahedron 1992, 48, 3365.
Acknowledgments
This work was supported by a grant (BioGreen21 Pro-
ject) from the Rural Development Administration,
Korea. We also thank Brain Korea 21 program.
12. Kim, J. H.; Curtis-Long, M. J.; Kim, J. Y.; Park, K. H.
Org. Lett. 2004, 6, 2273.
13. Kim, J. H.; Curtis-Long, M. J.; Seo, W. D.; Ryu, Y. B.;
Yang, M. S.; Park, K. H. J. Org. Chem. 2005, 70, 4082.
14. Jeong, H. J.; Lee, J. M.; Kim, M. K.; Lee, S.-G.
J. Heterocycl. Chem. 2002, 39, 1019.
Supplementary data
Supplementary data associated with this article can be
15. Enzyme activity test: a-L-rhamnosidase activity was
assayed using p-nitrophenyl a-L-rhamnopyranoside
(PNLR) as a substrate and a-rhamnosidase from P.
decumbens according to the method of Chapman et al.10b
The reaction mixture, containing 50 lL of enzyme solu-
tion (33 lg/mL), 100 lL of 2.5 mM p-nitrophenyl a-L-
rhamnopyranoside, 50 lL of sample solution and 50 lL of
50 mM phosphate buffer (pH 6.7) were incubated at 30 °C
for 20 min. After the addition of 100 lL of 0.4 M NaOH
to stop the reaction, absorbance of the mixture at 405 nm
was determined.
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