6448
S. Desvergnes et al. / Bioorg. Med. Chem. 15 (2007) 6443–6449
2. (a) O’Brien, R. J.; Nunn, P. P. Am. J. Respir. Crit. Care
Med. 2001, 163, 1055–1058; (b) Zhang, Y.; Amzel, L. M.
Curr. Drug Targets 2002, 3, 131–154.
incubated with UGM (8.2 nm) for 10 min at room tem-
perature in 50 lL of 100 mM potassium phosphate buf-
fer (pH 7.5). After the pre-incubation, 10 lL of freshly
prepared sodium dithionite (100 mM) was added to
the solution to reduce UGM and then 20 lL of UDP-
galactofuranose (UDP-Galf, 0.2 mM) was added as a
substrate. The concentrations of sodium dithionite and
UDP-Galf in the reaction mixture were 12.5 mM and
50 lM, respectively. The reaction was carried out at
37 ꢁC for 2 min, and the resulting mixture was immedi-
ately frozen by liquid nitrogen to terminate the reaction.
The reaction mixture was analyzed by HPLC using a
C18 column (Microsorb-MV, Varian, 4.6 · 250 mm)
with the detector set at 262 nm. Two eluting methods
were examined to determine the conversion of UDP-
Galf to the product UDP-galactopyranose (UDP-Galp).
3. See for example: (a) Takayama, K.; Kilburn, J. O.
Antimicrob. Agents Chemother. 1989, 33, 1493–1499; (b)
Wen, X.; Crick, D. C.; Brennan, P. J.; Hultin, P. G.
Bioorg. Med. Chem. 2003, 17, 3579–3587; (c) Gobec, S.;
ˇ
Plantan, I.; Mravljak, J.; Svajger, U.; Wilson, R. A.;
Besra, G. S.; Soares, S. L.; Appelberg, R.; Kikelj, D. Eur.
J. Med. Chem. 2006, 1–10.
4. (a) Rastogi, N.; Goh, K. S.; David, H. L. Antimicrob.
Agents Chemother. 1990, 34, 759–764; (b) Barry, C. E.
Biochem. Pharmacol. 1997, 54, 1165–1172; (c) Pan, F.;
Jackson, M.; Ma, Y.; McNeil, M. R. J. Bacteriol. 2001,
183, 3991–3998.
5. Pedersen, L. L.; Turco, S. J. Cell. Mol. Life Sci. 2003, 60,
259–266.
6. (a) Cren, S.; Gurcha, S. S.; Blake, A. J.; Besra, G. S.;
Thomas, N. S. Org. Biomol. Chem. 2004, 2, 2418–2420; (b)
Rose, N. L.; Completo, G. C.; Lin, S.-J.; McNeil, M.;
Palcic, M. M.; Lowary, T. L. J. Am. Chem. Soc. 2006, 128,
6721–6729; (c) Mikusova, K.; Belanova, M.; Kordulak-
ova, J.; Honda, K.; McNeil, M. R.; Mahapatra, S.; Crick,
D. C.; Brennan, P. J. J. Bacteriol. 2006, 188, 6592–6598;
(d) Wing, C.; Errey, J. C.; Mukhopadhyay, B.; Blanchard,
J. S.; Field, R. A. Org. Biomol. Chem. 2006, 4, 3945–3950;
(e) Kremer, L.; Dover, L. G.; Morehouse, C.; Hitchin, P.;
Everett, M.; Morris, H. R.; Dell, A.; Brennan, P. J.;
McNeil, M. R.; Flaherty, C.; Duncan, K.; Besra, G. S. J.
Biol. Chem. 2001, 276, 26430–26440.
3.10.1. Method 1. Mobile phase was 0.5% acetonitrile in
50 mM triethylammonium acetate buffer, pH 6.8. Flow
rate was at 1.0 mL/min. Under these conditions, UDP-
Galp and UDP-Galf were eluted at 6.1 and 7.6 min,
respectively.
3.10.2. Method 2. Mobile phase A: 50 mM potassium
phosphate buffer (pH 7.0) containing 2.5 mM tetrabuty-
lammonium hydrogen sulfate (TBAHS). Mobile phase
B: 50% acetonitrile in 50 mM potassium phosphate buf-
fer (pH 7.0) containing 2.5 mM TBAHS.20 The sample
was loaded on the column and eluted isocratically with
mobile phase A containing 4% mobile phase B. The elu-
tion rate was 0.55 mL/min. Under these conditions,
UDP-Galp and UDP-Galf were eluted at 10.9 and
12.6 min, respectively.
7. Escherichia coli UGM: (a) Sanders, D. A. R.; Staines, A.
G.; McMahon, S. A.; McNeil, M.; Whitfield, C.; Nai-
smith, J. H. Nat. Struct. Biol. 2001, 8, 858–863; Myco-
bacterium
tuberculosis
UGM:
(b)
Beis,
K.;
Srikannathasan, V.; Liu, H.; Fullerton, S. W. B.; Bam-
ford, V. A.; Sanders, D. A. R.; Whitfield, C.; McNeil, M.
R.; Naismith, J. H. J. Mol. Biol. 2005, 348, 971–982.
8. (a) Barlow, J. N.; Girvin, M. E.; Blanchard, J. S. J. Am.
Chem. Soc. 1999, 121, 6968–6969; (b) Zhang, Q.; Liu, H.-w.
J. Am. Chem. Soc. 2000, 122, 9065–9070; (c) Zhang, Q.; Liu,
H.-w. J. Am. Chem. Soc. 2001, 123, 6756–6766; (d)
Fullerton, S. W. B.; Daff, S.; Sanders, D. A. R.; Ingledew,
W. J.; Whitfield, C.; Chapman, S. K.; Naismith, J. H.
Biochemistry 2003, 42, 2104–2109; (e) Soltero-Higgin, M.;
Carlson, E. E.; Gruber, T. D.; Kiessling, L. L. Nat. Struct.
Mol. Biol. 2004, 11, 539–543; (f) Miller, S. M. Nat. Struct.
Mol. Biol. 2004, 11, 497–498.
The residual activity of UGM in the presence of individ-
ual iminogalactitol derivative was evaluated by dividing
the conversion in the presence of each derivative with
that in the absence of the derivatives. The results are
summarized in Table 1.
Acknowledgment
9. (a) Lee, R. E.; Smith, M. D.; Nash, R. J.; Griffiths, R.
C.; McNeil, M.; Grewal, R. K.; Yan, W.; Besra, G. S.;
Brennan, P. J.; Fleet, G. W. J. Tetrahedron Lett. 1997,
38, 6733–6736; (b) Lee, R. E.; Smith, M. D.; Pickering,
L.; Fleet, G. W. J. Tetrahedron Lett. 1999, 40, 8689–
8692; (c) Veerapen, N.; Yu, Y.; Sanders, D. A. R.; Pinto,
B. M. Carbohydr. Res. 2004, 339, 2205–2217; (d) Liau-
tard, V.; Desvergnes, V.; Martin, O. R. Org. Lett. 2006,
8, 1299–1302; (e) Liautard, V.; Christina, A. E.; Des-
vergnes, V.; Martin, O. R. J. Org. Chem. 2006, 71, 7337–
7345.
´
This work was supported by the CNRS, the Universite
Joseph Fourier, and the Agence Nationale pour la
Recherche (Grant No. ANR-05-JCJC-0130-01). H-w.L.
is grateful for the grant support from Welch Foundation
(F-1511). S.D. also thanks the LEDSS for financial
support.
Supplementary data
10. (a) Caravano, A.; Mengin-Lecreulx, D.; Brondello, J.-M.;
Vincent, S. P.; Sinay, P. Chem. Eur. J. 2003, 9, 5888–5898;
Supplementary data associated with this article can be
¨
(b) Caravano, A.; Vincent, S. P.; Sinay, P. Chem.
¨
Commun. 2004, 1216–1217; (c) Sadeghi-Khomani, A.;
Blake, A. J.; Wilson, C.; Thomas, N. R. Org. Lett. 2005, 7,
4891–4894; (d) Caravano, A.; Dohi, H.; Sinay, P.; Vincent,
¨
References and notes
S. P. Chem. Eur. J. 2006, 12, 3114–3123.
11. (a) Huang, Z.; Zhang, Q.; Liu, H.-w. Bioorg. Chem. 2003,
31, 494–502; (b) Caravano, A.; Vincent, S. P.; Sinay, P.
Bioorg. Med. Chem. Lett. 2006, 16, 1123–1125; (c) Itoh,
K.; Huang, Z.; Liu, H.-w. Org. Lett 2007, 9, 879–882.
¨
1. (a) Jarlier, V.; Nikaido, H. FEMS Microbiol. Lett. 1994,
123, 11–18; (b) Nguyen, L.; Thompson, C. J. Trends
Microbiol. 2006, 7, 304–312.