Chemistry: molecular biology and microbiology – Enzyme – proenzyme; compositions thereof; process for... – Hydrolase
Patent
1991-01-30
1992-08-18
Schwartz, Richard A.
Chemistry: molecular biology and microbiology
Enzyme , proenzyme; compositions thereof; process for...
Hydrolase
C12N 964
Patent
active
051399440
DESCRIPTION:
BRIEF SUMMARY
The present invention is concerned with collagen-specific enzymes with platelet aggregation inhibition properties; for brevity we will refer to such enzymes herein as collagenases.
The name collagenase is used for an important group of enzymes which specifically degrade collagen by means of hydrolytic scissions of peptide bonds in the helical regions when the collagen is in the native (undenatured) state. There are basically two types of collagenases:
(a) those making multiple non-specific hydrolytic scissions of the collagen molecule. This type of collagenase is elaborated by micro organisms that in themselves do not contain collagen;
(b) those which make a very limited number, typically one cut, per collagen molecule. This type of collagenase, the so-called tissue collagenases, is produced by mammals and other advanced animals that in fact have collagen as a major extracellular component of their tissues (Harris, E. D. and E. C. Cartwright 1977 in, Proteinases in Mammalian Cells and Tissues, Elsevier, pp 249-282).
Collagen is a structural protein which is virtually ubiquitous throughout the human body and bodies of higher animals. It is characterized by regions of small, repeating sequences of amino acids which result in the formation of helical chains between molecules. These helices give rise to its exceptional structural stability and strength. As a major constituent of connective tissue and skin, and the extracellular matrix (cement) which binds cells together, and as a major trigger in the aggregation of platelets collagen is of considerable physiological importance. An enzyme which specifically cleaves collagen should have a wide variety of medical and scientific applications.
Collagenases are widely distributed in nature in, for example, bacteria and vertebrate tissue. Bacterial collagenases, e.g. those produced by Clostridium histolyticum, are of the first type; that is, they cleave the collagen molecule at approximately 200 sites. This type is concerned with invasion of a host and, through degradation of the collagen molecule, with nutrition. Mammalian and other vertebrate collagenases are of the second type; that is, they cleave collagen at only one specific site. This type is concerned with repair of tissues, removing injured collagen, and remodelling of specialized tissues at a particular time of development or physiological expression, e.g. resorption of the tadpole tail or involution of the postpartum uterus. Following biochemical extraction and purification, tissue collagenases occur in latent form which requires specific activation. Harris, E. D. and E. C. Cartwright 1977, in, Proteinases in Mammalian cells and tissues, Elsevier, pp 249-282; Cawston, T. E. and G. Murphy 1981. Methods Enzymol 80, pp 711-734. This property severely limits the commercial usefulness of the known tissue collagenases. In fact relatively little is known about tissue collagenase because of the technical difficulties of having active enzyme in pure form.
This invention is concerned with a new type of tissue collagenase which occurs in active form following extraction. This active type of collagenase can be derived from the cephalic tissue of leeches. We have now isolated this new type of tissue collagenase from a variety of arhynchobdellid and rhynchobdellid leech species, including members of the family Hirudinidae, e.g. Hirudo medicinalis, Hirudinaria manillensis and Poecilobdella granulosa; the family Haemadipsidae e.g. Haemadipsa zeylanica and Haemadipsa picta; and the family Glossiphoniidae, e.g. Haementeria ghilianii (all the above being as defined in "Leech Biology and Behaviour" by Dr. R. T. Sawyer, Oxford University Press, 1986).
According to the invention, therefore, there is provided a collagenase which is such that it cleaves native (undenatured) collagen at a single site, said collagenase being characterised by the fact that it is leech derived.
The leech collagenase according to the invention belongs to the tissue type of collagenases in that it cleaves at a single primary site of the collagen molecu
REFERENCES:
patent: 3646195 (1972-02-01), Eriksson et al.
patent: 4390630 (1983-06-01), Sawyer et al.
patent: 4588587 (1986-05-01), Gasic
patent: 4788149 (1988-11-01), Cerami et al.
Stricklin et al. Biochemistry vol. 16 #8, 1977 p. 1607 Human Skin Collagee: Isolation of Precursor and Active Forms From Both Nibroblast and Organ Cultures.
Iraqi Fuad
Levy Haim
Rigbi Meir
Sawyer Roy T.
Biophram (UK) Limited
Nolan S.
Schwartz Richard A.
Yissum Research Development Company of the Hebrew University of
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