Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1997-01-15
1998-08-25
Kunz, Gary L.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
514 23, 514 25, 536 111, 536 41, 536 172, 5361231, A61K 31735, A61K 3170, C07H 100, C07H 1312
Patent
active
057983437
DESCRIPTION:
BRIEF SUMMARY
This case is filed under 35 USC 371 as the U.S. atage of PCT/EP95/02780 filed Jul. 14, 1995.
AREA OF THE INVENTION
The present invention relates to 7-O-carbamoylheptose derivatives, to a process for their production and to their use for the production of reagents and compositions for the diagnosis and therapy of pseudomonas infections in humans and animals, and to a screening process for their determination in Gram-negative bacteria.
BACKGROUND OF THE INVENTION
Bacteria of the Pseudomonadaceae family are Gram-negative organisms which occur ubiquitously and whose pathogenicity for humans is normally very weakly developed. P. aeruginosa, by contrast, is a human-pathogenic species and occurs frequently in wound infections and there especially as secondary infection in cases of higher-degree burns of the skin, and in cases of suppurative otitis media. In immunocompromised patients and in cases of cystic fibrosis it is particularly the antibiotic-resistant J. Trauma 21 (1981) 753-763. Bodey et al., Rev. Inf. Dis., 5 (1983), 279-313, Winkler et al., Klin. Wochenschrift, 63 (1985) 490-498!.
In terms of taxonomy, pseudomonads comprise a very heterogeneous family. Their species-related heterogeneity represents a considerable impediment to the medical diagnosis and therapy of pseudomonas infections. This is why it was only recently proposed that this family of Pseudomonadaceae be Leeuwenhoek, 64 (1993) 231-251!. The first group (RNA group 1) includes P. aeruginosa, P. fluorescens and P. putida. The second group (RNA group 2) comprises the pseudomonads which are pathogenic for plants and animals (for example P. plantarii) and is now referred to as burkholderia. Finally, a distinction is also made between comamonas (group 3) and the purple bacteria (group 4) which continue to be referred to as "pseudomonas" (for example P. diminuta, P. vesicularis) and lastly also xanthomonas (RNA group 5).
Beyond this, pseudomonads are also of biomedical interest for other al., Antimicrob. Agents Chemother., 36 (1985) 58-73!. There is evidence that this antibiotic resistance is associated with the structure of the cell wall membrane, that is to say with a high density of negatively E. W. Hancock et al., in: Bacterial Cell Wall, J. M. Ghuysen and R. Hakenbeck (eds.), Elsevier Amsterdam, 1994, 263-279). Such surface structures are in all Gram-negative bacteria essentially integral proteins of the cell membrane (OMP, porins) and the lipopolysaccharide (LPS, endotoxin). These molecules represent antigens which show high genus-, species- and subspecies-specific immunogenicity and, during the course of an infection, induce serotype-specific antibodies which may be of great importance to both diagnosis and therapy.
Over the course of the last decade it has been possible to acquire considerable knowledge about the serological and biological properties of these antigens. There has also been intensive study and elucidation of the LPS structures and there particularly of their immunogenic outer components (O chains) of the 17 serotypes now known. There has been complete chemical analysis of all P. aeruginosa O chains, and some of them have also been synthesized and classified serologically into various A. Knirel, Sov. Sci. Rev. B. Chem. 13 (1989) 1-101!. Based on this structural knowledge, various P. aeruginosa serotyping kits with monoclonal antibodies have been produced and are still commercially available. The disadvantage of these antibody test cocktails is that they detect only the known antibodies, but all monoclonal O-specific antibodies are necessary in order to detect all O types.
Besides the antigenic assay processes which have been known for a long time for the immunologically highly specific O chains, there has recently been development of cross-reacting monoclonal antibodies whose epitope is located not in the highly variable O chain of the lipopolysaccharide but in the less variable core oligosaccharide. Since these structures make essential contributions to the function of the outer cell membrane, core oligosaccharides are
REFERENCES:
Gerald P. Bodey et al., "Infections Caused by Pseudomonas Aeruginosa", Reviews of Infectious Diseases, vol. 5 No. 2, pp. 279-313, Mar.-Apr., 1983.
U. Winkler et al., "Pseudomonas Aeruginosa Infections of the Respiratory Tract in Cystic Fibrosis Patients", Klinische Wochen-Schrift, vol. 63, pp. 490-498, 1985.
Norberto J. Palleroni, "Pseudomonas Classification", Antonie Van Leenwenhoek, vol. 64, pp. 231-251, 1993.
Andrew M. Kropinski et al., "Structure and Functions of Pseudomonas Aeruginosa Lipopolysaccharide", Antibiot. Chemother., vol. 36, pp. 58-73, 1985.
Robert E.W. Hancock et al., "Molecular Organization and Structural Role of Outer Membrane Macromolecules," Bacterial Cell Wall, chapter 12, pp. 263-279, 1994.
N.K. Kochetkov et al., "The Structures of O-Specific Polysaccharides of Bacterium Pseudomonas Aeruginosa", Soviet Scientific Reviews B. Chem., vol. 13, pp. 1-101, 1989.
F.E. Di Padova et al., "A broadly Cross-Protective Monoclonal Antibody Binding to Escherichia coli and Salmonella Lipopolysaccharides", Infection and Immunity, vol. 61 No. 9, pp. 3863-3872, Sep., 1993.
Peter S.N. Rowe et al., "Structure of the Core Oligosaccharide from the Lipopolysaccharide of Pseudomonas Aeruginosa PAC1R and Its Defective Mutants", Euro. Biochem. 132, pp. 329-337, 1983.
Eleonora Altman et al., "A Novel Approach to the Structure Elucidation of the Core Region of the Lilpopolysaccharide from Pseudomonas Aeruginosa 06 (HABS) Rough-Type Mutant R5", XVIth Inter. Carbohydrate Symposium, p. 626, Jul. 5-10, 1992.
E. Altman et al., "A Novel Approach to the Structure Elucidation of the Core Region of Lipopolysaccharides. Structure of the Pseudomonas Aeruginosa 06 (Habs) LPS Core Oligosaccharide.", 2nd Conference of the Intern. Endotoxin Society, p. 55, Aug. 18, 1992.
William F. McManus, M.D., F.A.C.S., et al., "Burn Wound Infection", The Journal of Trauma, vol. 21 No. 9, pp. 753-756, Sep., 1981.
Beckmann Frank
Moll Hermann
Zahringer Ulrich
Forschungsinstitut Borstel Institut fur Experimentelle Biologie
Kunz Gary L.
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