Binding of pathological forms of prion proteins

IPC classes for russian patent Binding of pathological forms of prion proteins (RU 2309410):

G01N33/68 - involving proteins, peptides or amino acids

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FIELD: medicine, diagnostics.

SUBSTANCE: the method for selective binding of aggregating abnormal form of [protein at the presence of nonaggregating normal form of this protein deals with contacting under conditions of selective binding of the material containing the above-mentioned abnormal form and normal form, with a binding agent. Moreover, the binding agent is polyionic material that has got the avidity of binding towards the mentioned aggregating form of the mentioned protein being present in the sample. The conditions of selective binding deal with the presence of a competitive agent in the solution. The competitive agent has got ionic groups that have the least avidity of binding towards abnormal group of this protein in comparison with a binding agent. The above-mentioned binding should be determined qualitatively or quantitatively due to carrying out the immunoassay upon aggregating form of the protein. As binding agents one should apply polyanionic materials (pentosan polysulfate, dextran sulfate and others) or polycationic materials hexadimetrin, polybren and others). Binding agent could be immobilized upon solid medium. Application of the present innovation enables to increase sensitivity and specificity of diagnostic tests to prion diseases.

EFFECT: higher efficiency.

37 cl, 1 dwg, 16 ex

The text descriptions are listed faxing

1. Process for the selective binding of an aggregating abnormal form of the protein in the presence neogregarine normal form of this protein, providing contacts in terms of selective binding material containing as specified abnormal and normal forms, and the binding agent, which is a polyionic material having avidity binding in respect of the specified aggregation the specified form of the protein present in the sample, where the specified conditions of selective binding include the presence of a competitive agent in the solution, and competitive agent has an ionic group with lower avidity binding in respect of abnormal forms of this protein than polyionic material.

2. The method according to claim 1 where the binding agent is resistant to proteases.

3. The method according to claim 1 or 2, where the protease is present during the specified link or where this protein is subjected to the action of the protease after its binding.

4. The method according to claim 1 or 2 where the binding agent is a polyanionic material having multiple anionic groups, or poly material with multiple cationic groups.

5. The method according to claim 4, where the specified polyion the second material has many anionic groups, which are sulfate, carboxyl or phosphate groups, or multiple cationic groups are amino groups, aminopropane or Quaternary ammonium groups.

6. The method according to claim 5, where the specified polyionic material is a polyanionic polyglycosides.

7. The method according to claim 6, where the polyanionic polyglycoside is polysulfonyl polyglycosides.

8. The method according to claim 7, where the polyanionic polyglycoside is a polyanionic derivative of pentosan or a derivative of dextran.

9. The method of claim 8, where polysulfonyl polyglycoside is a polysulfate of pentosan (PPS) or dextran sulfate.

10. The method according to claim 4, where the specified polyionic material is a bromide hexadimethrine, dendrimer FRAMES, poly-L-lysine, pDADMAC or polyethylenimine.

11. The method according to any one of claims 1, 2, 5-10, where competitive agent has a lower density of ionic groups than polyionic material.

12. The method according to claim 11, where the competitive agent is anionic.

13. The method according to item 12, where the competitive agent is an anionic detergent.

14. The method according to item 12, where the competitive agent is an amide derivatives of fatty acids, obtained by the condensation of amino acid.

15. The method according to 14, where the competitive agent is N-lauroylsarcosine.

16. The method according to any one of claims 1, 2, 5-10, 12-15, where the pH is such that it article is mulroy specified binding of a binding agent with abnormal form of the protein.

17. The method according to clause 16, where pH is 8-9.

18. The method according to 17, where the pH is equal to 8,2-8,6.

19. The method according to any one of claims 1, 2, 5-10, 12-15, 17-18, where there is a detergent, which stimulates the binding of a binding agent with abnormal form of the protein.

20. The method according to any one of claims 1, 2, 5-10, 12-15, 17-18, where the specified binding agent after binding with the specified aggregated abnormal form of the protein is captured by immobilized breathtaking agent.

21. The method according to claim 20, where the specified breathtaking agent is a lectin or antibody reactive with the specified binding agent.

22. The method according to claim 20, where the specified binding agent is provided to selectively connect the marker group and the Exciting agent is associated with the specified marker group.

23. The method according to any one of claims 1, 2, 5-10, 12-15, 17-18, where the binding agent immobilized on solid medium before exposure specified abnormal form of the protein.

24. The method according to item 23, where the environment is a substrate having deposited in the form of a coating specified binding agent.

25. The method according to item 23, where the binding agent selectively provide associated marker group and immobilized on the specified hard environment through the specified marker group.

26. The method according to item 22 or 25, where the specified link marker group is Biotin, fluorescein, dinitrophenol, di is othenin, the sequence of the nucleic acid or analogue of the nucleic acid or (His)6.

27. The method according to any one of claims 1, 2, 5-10, 12-15, 17-18, where the specified binding agent is a solid material that provides the surface with the specified avidity binding.

28. The method according to item 27, where this surface is the surface of the polymer having ion troupe, covalently linked in the structure of this polymer or formed by modification of the surface groups of the polymer.

29. The method of analysis for the presence of abnormal aggregating form of the protein in the sample, providing the binding specified abnormal form of the protein by the method according to any of the preceding paragraphs with subsequent determination of the presence or amount of binding protein with a binding agent.

30. The method according to clause 29, where the specified binding determine qualitatively or quantitatively by conducting immunoassay for aggregating form of this protein.

31. The method according to clause 29 or 30, where the binding of the abnormal aggregating form of the protein is conducted selectively in the presence of normal neogregarine form of the protein and then associated protein aggregated form is separated from unbound protein normal form and then carry out the specified determining the presence or quantity of the specified binding.

32. The method according to clause 29 or 30, where this anomalous f the RMA protein is PrP ^Scand the normal form is PrP^c.

33. The method according to claim 1, in which the abnormal aggregating form of the protein is PrP^Scand normal neogregarine form of the protein is PrP^cadditionally separating PrP^Scfrom PrP^cby selective binding of PrP^Scthe binding agent in the presence of an amide derivative of a fatty acid, obtained by the condensation of amino acid.

34. The method according to p, where amide derived fatty acids, obtained by the condensation of an amino acid is N-lauroylsarcosine.

35. The method according to at p or 34 conducted at pH 8-9.

36. Binding agent for an aggregating abnormal form of the protein, which is hexadimethrine or poly-linking agent, conjugated with associated marker group, whereby this binding agent may be immobilized on a solid medium by associating the specified link marker group with breathtaking agent on the specified hard environment.

37. Selective binding agent p, which is poly material selected from bromide hexadimethrine, dendrimers FRAMES, poly-L-lysine, pDADMAC or polyethylenimine.