Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1985-09-12
1989-04-04
Rollins, John W.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
424 941, 530358, 514885, A61K 3700, A61K 3748
Patent
active
048187631
DESCRIPTION:
BRIEF SUMMARY
Numerous and various thymus preparations are known. They also include the thymus preparation (HTH) according to Comsa & Bernardi ("Extraction, Fractionation and Testing of a Homogeneous Thymic Hormone Preparation", published in Annals of the New York Academy of Sciences, Vol. 240, Feb. 28, 1975, pp. 402-403).
Cosma was able to show, among other things, that HTH possesses immune system-immunostimulating and endocrinologically active properties. He suspected that this effect can be attributed to a special thymic hormone ("Hormonal Coordination of the Immune Response", Vol. 92, Springer-Verlag, 1982). Comsa also demonstrated that thymus preparations can be therapeutically ineffective or detrimental due to unclarified side effects of substances that are yet to be identified. Consequently, thymic preparations may contain substances which conceal or inhibit or interfere with the effective properties of the presumed thymic hormone within the thymic preparation and which can represent a considerable risk for the patient.
An objective of the present invention is to propose a biologically active substance of the above-described type which shows a clear relationship to the desired thymic hormone-like effect, i.e., is essentially free from foreign substances which can adversely affect this effect. The purpose primarily pursued herewith is mainly to create the possibility to standardize the effect of such a preparation and thus to open up ways for processes for the production of the active substance from bilogical starting materials, which practically yield pure preparations with hormone-like effects, which are free from foreign substances.
The task is accomplished by the invention characterized in the claims.
It was surprising for the inventors that they were unable to localize any specific thymic hormone possessing clearly immunological and endocrinological properties in the Comsa-Bernardi HTH thymus fraction. On investigations of HTH, it was possible to prepare two reproducibly detectable polypeptide chains, HTH.sub.a and HTH.sub.B as the hormonal active substances, whose amino-acid sequences surprisingly proved to be identical with the sequences of the H2A and H2B histones. The inventors were thus able to show for the first time ever that histones which had previously been known only as cell-nucleus proteins must possess hromone-like properties with extracellular and endocrine activities. Histone/thymic hormone structural comparisons showed that the hormone-like, especially thymic hormone-like properties of the histones are determined, at least essentially to a major extent, by the variable evolution parts of the histones (following description and FIG. 3 (A)) and that they cannot be found in the invariable evolution (constant) portions of the histone. The inventors were able to localize component sequences with hormonal effect (active histone sequences) by the structural comparisons in the variable evolution-histone segments of the H2 histones (following description and FIG. 3 (B)), which show similarities with thymic hormones. It was also possible to show that similarities especially exist with the N-terminal histone areas and interchangeable relationship which exist between histones and proteins of the immune system, especially ubiquitin.
Thus, it is disclosed in the present invention that histones, especially H2A and H2B histones and certain segments thereof possess hormone-like, especially thymic hormone-like properties and are not only constituents of the cell nucleus. It was also found that the immune system-immunostimulating and/or endocrinologically active substances, which are contained in the great variety of known thymus preparations, show similarities with the variable evolution segments of the histones and can therefore probably be included in a histone family which may have to be redefined concerning its newly discovered hormonal properties.
Thus, the present invention discloses relatively simple ways for the specific production of immune system-immunostimulating and/or endocrinologically active prep
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Jornvall Hans
Reichhart Robert
Rusch Volker
Zeppezauer Michael
Rollins John W.
Rusch Volker
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