A synthetic pentasaccharide with GTPase activity

Organic Letters

Volumn 3, Issue 26, 2001, Pages 4311-4314

  Solomon, Dmitry ^a   Fridman, Micha ^a   Zhang, Jeanwei ^a   Baasov, Timor ^a  

^a TECHNION ISRAEL INSTITUTE OF TECHNOLOGY   (Israel)

Author keywords

[No Author keywords available]

Indexed keywords

GUANOSINE DIPHOSPHATE; GUANOSINE TRIPHOSPHATASE; GUANOSINE TRIPHOSPHATE; OLIGOSACCHARIDE;

ARTICLE; CARBOHYDRATE ANALYSIS; CHEMISTRY; CONFORMATION; HYDROLYSIS; KINETICS; METABOLISM; MOLECULAR GENETICS; NUCLEAR MAGNETIC RESONANCE;

CARBOHYDRATE CONFORMATION; CARBOHYDRATE SEQUENCE; GTP PHOSPHOHYDROLASES; GUANOSINE DIPHOSPHATE; GUANOSINE TRIPHOSPHATE; HYDROLYSIS; KINETICS; MOLECULAR SEQUENCE DATA; NUCLEAR MAGNETIC RESONANCE, BIOMOLECULAR; OLIGOSACCHARIDES;

EID: 0035961027     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol010257h     Document Type: Article

References (23)

1. (a) Gurrier-Takada, C.; Altman, S. Science 1983, 223, 285.
2. (b) Zang, A. J.; Cech, T. R. Science 1986, 231, 470.
3. Breaker, R. R.; Joyce, G. F. Chem. Biol. 1994, 1, 223.
4. For recent reviews in this field see the following special issues: (a) "Frontiers in Carbohydrate Research" Chem. Rev. 2000, 291, 4265-4712.
5. (b) "Carbohydrates and Glycobiology" Science 2001, 291, 2337-2378.
6. For cyclodextrin-based catalytic systems, see: (a) Breslow, R.; Dong, S. D. Chem. Rev. 1998, 98, 1997.
7. (b) Han, M. J.; Yoo, K. S.; Chang, J. Y.; Ha, T.-K. Angew. Chem., Int. Ed. 2000, 39, 347. For ribose-containing catalytic polymers, see:
8. (c) Han, M. J.; Yoo, K. S.; Cho, T. J.; Chang, J. Y.; Cha, Y. J.; Nam, S. H. Chem. Commun. 1997, 163.
9. (d) Han, M. J.; Yoo, K.; Kim, K. H.; Lee, G. H. S.; Chang, J. Y. Macromolecules 1997, 30, 5408.
10. (a) Suzuki, S.; Higashiama, T.; Nakahara, A. Bioorg. Chem. 1973, 2, 145.
11. (b) Hosseini, M. W.; Lehn, J.-M.; Mertes, M. P. Helv. Chim. Acta 1983, 66, 2454.
12. (c) Hosseini, M. W.; Lehn, J.-M.; Jones, K. C.; Plute, K. E.; Mertes, K. B.; Mertes, M. P. J. Am. Chem. Soc. 1989, 111, 6330.
13. The monosaccharides 2-5 were prepared by standard methods. All new compounds exhibited satisfactory spectral and analytical data. Yields refer to spectroscopically and chromatographically homogeneous materials.
14. Veeneman, G. H.; van Leeuwen, S. H.; van Boom, J. H. Tetrahedron Lett. 1990, 31, 1331.
15. 1H NMR spectroscopy (H-1, δ 5.68, J = 8.4 Hz).
16. eq (small Δδ for α-anomers and larger Δδ for β-anomers: Imoto, M.; Kusunose, N.; Matsuura, Y.; Kusumoto, S.; Shiba, T. Tetrahedron Lett. 1987, 28, 6277). Complementary results were obtained by both methods in all molecules containing KDO (see Supporting Information).
17. eq (small Δδ for α-anomers and larger Δδ for β-anomers: Imoto, M.; Kusunose, N.; Matsuura, Y.; Kusumoto, S.; Shiba, T. Tetrahedron Lett. 1987, 28, 6277). Complementary results were obtained by both methods in all molecules containing KDO (see Supporting Information).
18. Complete NMR assignments for the monosaccharides 2-5 along with the protected oligosaccharides 7-8, 10, 11α, 11β and selected data for 1α and 1β are given in Supporting Information.
19. (11)DNAse activity was examined by using DNA plasmid pSL301 (Brosius, J. DNA 1989, 8, 759) as a substrate. The extent of DNA hydrolysis was monitored [in Tris/HCl (50 mM), DNA (16.7 μg/mL), 1 (6.2 mM), pH 7.5, 2 h, 55 °C] by measuring the relative quantities of the supercoiled (ccc). open-circular (oc), and linear (1) DNA forms by using agarose gel electrophoresis. The bis(p-nitrophenyl)phosphate was used as a substrate to determine the phosphodiesterase activity; the reaction progress was followed [in Tris/HCl (50 mM), bis (p-nitrophenyl) phosphate (0-20 mM), 1 (1.9 mM), pH 7.2, 50 °C] by UV spectroscopy (400 nm). In both cases, only moderate activities were determined (see Figures 1S and 2S in Supporting Information).
20. We note that the integral of the inorganic phosphate signal in Figure 1 (the spectra were acquired at a relaxation delay time of 0.5 s, 320 scans) appears to be less than that for either of the phosphate groups of GDP. This is attributed to the longer spin lattice relaxation time (T1) of inorganic phosphate than that for either phosphate group of GDP. Indeed, when the same spectra were recorded at the relaxation delay time of 10 s, 320 scans, integration of 1:1 was observed.
21. (a) Yohannes, P. G.; Plute, K. E.; Mertes, M. P.; Mertes, K. B. Inorg. Chem. 1987, 26, 1751.
22. (b) Maegley, K. A.; Admiraal, S. J.; Herschlag, D. Proc. Natl. Acad. Sci. U.S.A. 1996, 93, 8160.
23. We note that the preliminary experiments with pure diastereomers indicated that 1β is considerably more active than 1α (Scheme 2). Further kinetic and mechanistic studies are in progress and will be reported in due course.