Patent EA-005310-B1 (EA)
Title: Hypotensors
Inventor: ISHIDA YUICHI
IPC: C07K14/47
Filed: 2001-04-09
Abstract: 1. A method for selection of a substance capable of controlling activation of prorenin in which the method is carried out using, as an indicator, an adjusting ability of the activation of prorenin which occurs by protein-protein interaction in the profragment region of prorenin without alteration in a primary structure. 2. A method for selection of a substance capable of controlling activation of prorenin in which the method is carried out using, as an indicator, an adjusting ability of the activation of prorenin by an antibody against the profragment region of prorenin. 3. The method for selection according to claim 1 or 2, wherein the substance to be selected is a substance which is designed on the basis of information of at least three amino acid sequences of the amino acid sequence in the profragment region of prorenin. 4. The method for selection according to claim 1 or 2, wherein the substance to be selected is a substance which is designed on the basis of information of at least three amino acid sequences in from the first to the 19th or from 27th to the 41st amino acid sequence from N-terminal of the amino acid sequence in the profragment region of prorenin. 5. The method for selection according to claim 1 or 2, wherein the substance to be selected is a substance which is designed on the basis of information of at least three amino acid sequences in from the 5th to the 19th amino acid sequence from N-terminal of the amino acid sequence in the profragment region of prorenin. 6. The method for selection according to any of claims 3 to 5, wherein the substance to be selected is a peptide. 7. The method for selection according to any of claims 3 to 5, wherein the substance to be selected is a low-molecular compound. 8. The method for selection according to any of claim 1 to 7, wherein the prorenin is human prorenin. 9. The method for selection according to any of claims 1 to 7, wherein the prorenin is rat prorenin. 10. A prorenin activation controlling substance having a function of controlling activation of prorenin which occurs by protein-protein interaction in the profragment region of prorenin without alteration in a primary structure, said substance is a low-molecular compound, a compound derived from natural substances or a peptide. 11. A prorenin activation controlling substance having a function of controlling activation of prorenin which occurs by protein-protein interaction in the profragment region of prorenin without alteration in a primary structure, wherein the substance is selected by any of the methods mentioned in claims 1 to 9, said substance is a low-molecular compound, a compound derived from natural substances or a peptide. 12. A prorenin activation controlling substance having a function of inhibiting activation of prorenin which occurs by protein-protein interaction in the profragment region of prorenin without alteration in a primary structure, said substance is a low-molecular compound, a compound derived from natural substances or a peptide. 13. A prorenin activation controlling substance having a function of inhibiting activation of prorenin which occurs by protein-protein interaction in the profragment region of prorenin without alteration in a primary structure and retaining no renin-inhibiting activity, said substance is a low-molecular compound, a compound derived from natural substances or a peptide. 14. A prorenin activation controlling substance having a function of inhibiting activation of prorenin which occurs by protein-protein interaction in the profragment region of prorenin without alteration in a primary structure, wherein the substance is selected by any of the methods mentioned in claims 1 to 9, said substance is a low-molecular compound, a compound derived from natural substances or a peptide. 15. A prorenin activation controlling substance having a function of inhibiting activation of prorenin which occurs by protein-protein interaction in the profragment region of prorenin without alteration in a primary structure and retaining no renin-inhibiting activity, which is selected by any of the methods mentioned in claims 1 to 9, said substance is a low-molecular compound, a compound derived from natural substances or a peptide. 16. A prorenin activation controlling substance comprising a peptide having a partial sequence selected from amino acid sequence of profragment region of prorenin or an equivalent peptide thereto and having a function of inhibiting activation of prorenin which occurs by protein-protein interaction in the profragment region of prorenin without alteration in a primary structure. 17. A prorenin activation controlling substance comprising a peptide having a continued 3 to 10 partial sequence selected from amino acid sequence of profragment region of prorenin and having a function of inhibiting activation of prorenin which occurs by protein-protein interaction in the profragment region of prorenin without alteration in a primary structure. 18. A prorenin activation controlling substance comprising a peptide having a continued 3 to 8 partial sequence selected from amino acid sequence of profragment region of prorenin and having a function of inhibiting activation of prorenin which occurs by protein-protein interaction in the profragment region of prorenin without alteration in a primary structure. 19. A prorenin activation controlling substance comprising a peptide having a continued 3 to 6 partial sequence selected from amino acid sequence of profragment region of prorenin and having a function of inhibiting activation of prorenin which occurs by protein-protein interaction in the profragment region of prorenin without alteration in a primary structure. 20. A prorenin activation controlling substance comprising a peptide selected from the peptide mentioned in SEQ ID NO: 7 to NO: 14 of the Sequence Listing and having a function of inhibiting activation of prorenin which occurs by protein-protein interaction in the profragment region of prorenin without alteration in a primary structure. 21. A prorenin activation controlling substance comprising a peptide selected from the peptide mentioned in SEQ ID NO: 3, NO: 4 and from NO: 15 to NO: 20 of the Sequence Listing and having a function of inhibiting activation of prorenin which occurs by protein-protein interaction in the profragment region of prorenin without alteration in a primary structure. 22. A prorenin activation controlling substance having a function of inhibiting activation of prorenin which occurs by protein-protein interaction in the profragment region of prorenin without alteration in a primary structure, wherein the substance is a low-molecular compound designed from the information of amino acid sequence of profragment region of prorenin. 23. The prorenin activation controlling substance according to any of claims 16 to 22, wherein the substance has a function of inhibiting activation of prorenin which occurs by protein-protein interaction in the profragment region of prorenin without alteration in a primary structure and retains no renin-inhibiting activity. 24. The prorenin activation controlling substance according to any of claims 12 to 23, wherein an effect of inhibiting activation of prorenin is caused by an antagonistic action against the protein-protein interaction in the profragment region of prorenin, said substance is a low-molecular compound, a compound derived from natural substances or a peptide. 25. A prorenin activation controlling substance comprising an antibody against the profragment region of prorenin the sequence is selected from SEQ ID NO: 22-26 of the Sequence Listing which is capable of inhibiting the prorenin activation in vivo by removal of prorenin based on an antigen-antibody reaction to the profragment region of prorenin. 26. A hypotensor containing at least one of the prorenin activation controlling substances mentioned in any of claims 12 to 25 as an effective ingredient. 27. The hypotensor according to claim 26, wherein about 10% or more hypotensive rate is available as a hypotensive effect is about 10% or higher at least at the 12th hour after administration in vivo. 28. The hypotensor according to claim 26, wherein a hypotensive effect is selectively achieved only in patients suffering from hypertension. 29. An organ hypertrophy suppressor containing at least one of the prorenin activation controlling substances mentioned in any of claims 12 to 25 as an effective ingredient. 30. The organ hypertrophy suppressor according to claim 29, wherein an organ hypertrophy can be suppressed in heart and/or kidney. 31. An arterial thickening suppressor containing at least one of the prorenin activation controlling substances mentioned in any of claims 12 to 25 as an effective ingredient. 32. A method for a treatment of hypertension using any of the hypotensors mentioned in claims 26 to 28. 33. A method for a treatment of cardiac insufficiency or renal insufficiency using the organ hypertrophy suppressor mentioned in claim 29 or 30. 34. A method for a treatment of diseases accompanied by thickening of blood vessel using the arterial thickening suppressor mentioned in claim 31. 35. A method of selection a substance capable of inhibiting the prorenin activation without alteration in a primary structure, the method is carried using a system of the prorenin activation derived from an animal, not a human, the system is designed on the basis of information of a partial prorenin amino acid sequences of an animal, not a human, corresponding to the partial prorenin amino acid sequences of a human, which is involved in a human prorenin activation.