Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1995-04-27
1997-05-06
Cain, Edward J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
A61K 3800
Patent
active
056271549
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
This invention relates to polypeptides found in the venom of the Heteropoda venatoria spider and to polypeptides having substantially the same amino acid sequence and substantially the same activity as said polypeptides. The polypeptides and the pharmaceutically acceptable salts thereof block calcium channels in cells including neuronal and muscle cells of various organisms including invertebrates and vertebrates, This invention also relates to the use of said polypeptides and their salts in blocking calcium channels in cells such as cells in the nervous and muscular system of an organism, per se, and in the treatment of calcium channel mediated diseases and conditions in a mammal. Further, this invention relates to compositions comprising said polypeptides and salts thereof.
Compounds which are calcium antagonists have a variety of utilities. Calcium antagonists can find clinical application in the treatment of such conditions as angina, hypertension, cardiomyopathies, supraventricular arrhythmias, aesophogeal achalasia, premature labor and Raynaud's disease among others. See W. G. Nayler, Calcium Antagonists, Academic Press, Harcourt Brace Jovanovich Publishers, New York, N.Y. 1988, the teachings of which are incorporated herein by reference. Further, such compounds are useful in the study of the physiology of cells such as neuronal and muscle cells.
SUMMARY OF THE INVENTION
This invention concerns polypeptides found in the venom of the Heteropoda venatoria spider. The polypeptides of this invention and the fractions in which they are present according to this invention are as follows.
Heteropoda peptide AU 2 has the amino acid sequence, SEQ ID NO: 1. Heteropoda peptide AU 3 has the amino acid sequence, SEQ ID NO: 2. Heteropoda peptide AU 5A has the amino acid sequence, SEQ ID NO: 3. Heteropoda peptide AU 5B has the amino acid sequence, SEQ ID NO: 4. Heteropoda peptide AU 5C has the amino acid sequence, SEQ ID NO: 5. Heteropoda peptide KJ 1 has the amino acid sequence, SEQ ID NO: 6. Heteropoda peptide KJ 5 has the amino acid sequence, SEQ ID NO: 7. Heteropoda peptide KJ 6 has the amino acid sequence, SEQ ID NO: 8. Heteropoda peptide KJ 7 has the amino acid sequence, SEQ ID NO: 9.
The polypeptides of this invention block calcium channels in cells. Accordingly, these polypeptides are useful in blocking calcium channels in cells, per se. These polypeptides are also useful in the control of invertebrate pests and in the treatment of diseases and conditions in a mammal mediated by calcium channel function in cells.
Also within the scope of this invention are polypeptides which have substantially the same amino acid sequence and substantially the same calcium channel blocking activity as the polypeptides described above.
This invention also concerns pharmaceutical compositions comprising said polypeptides and methods of administering said polypeptides.
DETAILED DESCRIPTION OF THE INVENTION
Venom is obtained from the Heteropoda venatoria spider through the process of milking by electrical stimulation according to standard methods well known to those skilled in the art. It is preferred that the method employed is one which safeguards against contamination of the whole venom by abdominal regurgitant or hemolymph. Such methods are well known to those skilled in the art. The whole venom so obtained is stored in a frozen state at about -78.degree. C. until used for purification as described below. Purification of the constituents from the whole venom is accomplished by reverse phase high performance liquid chromatography (HPLC) on a variety of preparative and semi-preparative columns such as C-4 and C-18 Vydac.RTM. columns (Rainin Instrument Co. Inc., Mack Road, Woburn, Mass. 01801 ). Peak detection is carried out monochromatically at 220-230 nm. Further analysis of the fractions can be accomplished with, for example, polychrome UV data collected with a Waters 990 diode array detector (Millipore Corporation, Waters Chromatography Division, 34 Maple Street, Milford, Mass. 01757). Th
REFERENCES:
Proceedings of The Indian Academy of Science; 97,pp. 231-237, (1988).
J. Biological Chemsitry, 265, pp. 861-867, (1990).
Kelbaugh Paul R.
Saccomano Nicholas A.
Volkmann Robert A.
Cain Edward J.
Ginsburg P. H.
Pfizer Inc.
Richardson P. C.
Zielinski B. C.
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