Chemistry: natural resins or derivatives; peptides or proteins; – Proteins – i.e. – more than 100 amino acid residues – Blood proteins or globulins – e.g. – proteoglycans – platelet...
Patent
1995-04-10
1998-07-07
Housel, James C.
Chemistry: natural resins or derivatives; peptides or proteins;
Proteins, i.e., more than 100 amino acid residues
Blood proteins or globulins, e.g., proteoglycans, platelet...
435 731, 4353201, C12P 2108
Patent
active
057770832
DESCRIPTION:
BRIEF SUMMARY
This invention concerns stress protein epitopes intended inter alia for use in diagnosis and treatment of disease states in which stress proteins are produced.
Environmental stress can induce an increase in the rate of synthesis of so-called heat shock, or stress, proteins in both procaryotic and eucaryotic cells (see for example Schlesinger et al (eds) in: Heat Shock from Bacteria to Man, Cold Spring Harbor, N.Y., (1972)). Although the function of the stress proteins has yet to be finally resolved, some have been reported to participate in assembly and structural stabilisation of certain cellular and viral proteins, and their presence at high concentration may have an additional stabilising effect during exposure to adverse conditions.
Many pathogenic organisms have been shown to produce stress proteins (see Young et al, Proc. Natl. Acad. Sci. USA, 85, 4267-4270 (1988)). The proteins are thought to be produced in response to the stress of infection to help protect the invading pathogen. Thus, for example, the ability to produce stress proteins has been implicated in the survival of bacterial pathogens within macrophages (Christmas et al, Cell, 41, 753-762 (1985) and Morgan et al, Proc. Natl. Acad. Sci. USA, 83, 8059-8063 (1986)).
Burnie et al, (GB 90307236.1, WO 92/01717), have found that stress proteins from both fungi and bacteria, for example, Candida albicans and Corynebacterium leikium, comprise an immunodominant conserved antigen. The carboxy end of the Candidal stress protein has been sequenced and an antibody raised against the epitope LKVIRKNIVKKMIE found to recognise both the 47 and 92 Kd Candidal stress proteins in sera from patients suffering from systemic Candidal infection. In addition, the antibodies also recognised stress proteins in sera of patients suffering from other fungal infection, for example, the 40 and 88/84 Kd Aspergillus stress proteins, as well as stress proteins in sera from patients suffering from bacterial infection, for example, the 52 and 86 Kd Coryneform stress proteins. Other peptide sequences from the Candidal stress protein were found to be immunogenic, for example, the epitopes LSREM, LKVIRK and STDEPAGESA reacted with sera from patients with systemic candidiasis.
The entire human 89 kDa heat shock protein (HSP90) gene has been sequenced (Hickey et al, Mol. Cell. Biol., 9, 2615-2626, 1989) and its amino acid sequence deduced and compared to that of heat shock proteins of other species. Although it appears that the class of heat shock proteins is highly conserved among species, direct comparison and identification of common functional sequences (i.e. epitopes) of the heat shock proteins have not been reported.
It is now found that, notwithstanding the efficacy of the earlier described epitopes, routes to production, other than from the carboxy sequence of the candidal HSP90, can give equal or potentially superior results when used in diagnosis or therapy.
According to the present invention there is provided a functional epitope which is purified from human HSP 90 or which is synthesised to correspond to such a purified epitope, which is, if purified, unchanged or changed by substitution of selected amino acids and if synthesised is identical to a purified epitope or differs from a purified epitope by substitution of selected amino acids, and which cross-reacts with an antibody raised against a stress protein.
The epitope may comprise the amino acid sequence XXXLXVIRKXIV, or XXILXVIXXXXX, wherein X is any amino acid, and may comprise, for example, the amino acid sequence NKILKVIRKNIV.
The epitope may be selected from the amino acid sequences KIRY, NNLGTI, QFIGYPI, KKIK, SKEQV or Candidal equivalent sequence SIKAV, GLELPE or Candidal equivalent sequence FELEES, LDKK or Candidal equivalent sequence LGDQ, WTAN or Candidal equivalent sequence WSAN, NSTMGY or Candidal equivalent sequence TTMSSY, PIVET or Candidal equivalent sequence PIIKE, or KNDK or Candidal equivalent sequence AEDK.
The stress protein may comprise a malarial stress protein, a fungal stress protein or a ba
REFERENCES:
patent: 5188964 (1993-02-01), McGuire
patent: 5288639 (1994-02-01), Burnie et al.
patent: 5447843 (1995-09-01), McGuire
patent: 5474892 (1995-12-01), Jakob et al.
patent: 5541077 (1996-07-01), Burnie et al.
Matthews, R.C., et al., "Autoantibody To Heat-Shock Protein 90 Can Mediate Protection Against Systemic Candidosis," Immunology, 1991, vol. 74, pp. 20-24.
Hickey, Eileen, et al., "Sequence And Regulation Of A Gene Encoding A Human 89-Kilodalton Heat Shock Protein," Molecular And Cellular Biology, 1989, vol. 9, No. 6, pp. 2615-2626.
Burnie, James P., et al., "Heat Shock Protein 88 And Aspergillus Infection," Journal Of Clinical Microbiology, 1991, vol. 29, No. 10, pp. 2099-2106.
Matthews, R.C., "HSP 90, Yeasts And Corynebacterium Jeikeium," Epidemiology And Infection, 1991, vol. 107, pp. 273-283.
Matthews, Ruth, et al., "The Application Of Epitope Mapping In The Development Of A New Serological Test For Systemic Candidosis," Journal Of Immunological Methods, 1991, vol. 143, pp. 73-79.
Matthews et al, Epiderm. & Infect., 1991, vol. 107, pp. 273-283.
Matthews et al, Immunology, vol. 74, 1991, pp. 20-24.
Jendoubi, M et al, Nucleic Acids Res., vol. 16(22) 1988, p. 10928.
Binart, N. et al, Biochem. Biophys, Res. Comm., 1989, vol. 159(1), pp. 140-147.
Shinnick, T.M, 1991, vol. 167, pp. 145-160, Curr. Top. Microbiol. Inamun.
Lehner, T. et al, Infect & Immun., Apr. 1991, vol. 59(4) pp. 1434-1441.
Hoffmann, T et al, Gene, vol. 74, 1988, pp. 491-501.
Moore, SK et al, J. Biol. Chem., vol. 264(10) Apr. 5, 1989, pp. 5343-5351.
Hickey, E. et al, Mol. & Cell. Bio, Jun. 1989, vol. 9(6), pp. 2615-2626.
Matthews, R.C., J. Med. Microbiol, vol. 36, 1992, pp. 367-370.
Moore, S. K et al, DNA & Cell Bio.,vol. 9(6) 1990, pp. 387-400.
Rebbe, N.F. et al, Gene, vol. 53, 1987, pp. 235-245.
Yamazaki, M et al, Agric. Biol. Chem., vol. 54(12) pp. 3163-3170, 1990.
Yamazaki, M et al, Nucleic Acids Res., vol. 17(17), 1989.
Farrelly, FW et al, J. Analy. Chem., vol. 259(9), May 1984, pp. 5745-5741.
Gaston, JSH, Int. J. Clin. Lab Res., vol. 22, pp. 90-94, 1992.
Kumar, N et al, Infect. Immun, May 1990, vol. 58(5), pp. 1408-1404.
Matteir D et al, J. Immunol, Oct. 1989, vol. 19(10), pp. 1823-1828.
Sharma, D., Comp. Biochem. Physiol., Jul. 1992, vol. 102(3) pp. 437-444.
Ozawa, K et al, Genomics, vol. 12, 1992, pp. 214-220.
Matthews et al, J. of Imm. Methods, vol. 143, 1991, pp. 73-79.
Jung, G et al, Angewandte Chemie, vol. 31(4), Apr. 1992, pp. 367-486.
Geysen, HM et al, J. Mol. Recognit., vol. 1(1), pp. 32-41, Feb. 1988.
Guglielmi, G. et al, J. Bact., Nov. 1991, vol. 173(22), pp. 7374-7381.
Burnie James Peter
Matthews Ruth Christine
Housel James C.
NeuTec Pharma plc
Portner Ginny Allen
LandOfFree
Stress protein epitopes does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Stress protein epitopes, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Stress protein epitopes will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1207240