Chemistry: natural resins or derivatives; peptides or proteins; – Peptides of 3 to 100 amino acid residues – 25 or more amino acid residues in defined sequence
Patent
1994-12-16
1996-07-30
Wax, Robert A.
Chemistry: natural resins or derivatives; peptides or proteins;
Peptides of 3 to 100 amino acid residues
25 or more amino acid residues in defined sequence
435 692, 4352523, 4353201, 536 231, A61K 3800, C07H 2104, C12P 2106, C12N 120
Patent
active
055412882
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to a novel peptide having a pharmacologically useful activity and a producing method thereof. The peptide is prepared by altering a part of amino acids which constitute a peptide having a normal protease inhibitory activity.
BACKGROUND OF THE INVENTION
Elastase, which is one of the proteolytic enzymes, has been said to play an important role in metabolism of living tissue. In particular, elastase, which is secreted from neutrophils which are one type of lymphocyte, is involved in infectious disease and inflammation of tissue, and may act in protection against infection and regeneration of damaged tissue. A protein having elastase inhibitory activity is also produced in the living body, and it acts to prevent excessive degradation of the living tissue by neutralizing the excess elastase activity [Ann. Rev. Med., 36:207-216, (1985)].
As stated above, the balance between the activity of elastase and that of elastase inhibitory protein is strictly regulated and maintained in the living body. When this balance is disturbed various diseases can result. For example, when elastase activity is enhanced, diseases such as pulmonary emphysema, idiopathic pulmonary fibroma, and adult respiratory distress syndrome (ARDS) are caused in the lung [Metabolism, 29:41-49, (1992)], and an increase of neutrophil elastase activity in the joints is thought to be involved in generation of diseases such as rheumatoid arthritis and deformative arthritis [Agents Actions, 8:11-18 (1978); Bulletin of Pharmacological Society of Japan, 99:93-107 (1992)]. Further, elastase is thought to be involved in generation of acute and chronic inflammatory diseases [Ann. Rev. Med., 36:207-216 (1985)].
.alpha. 1-anti-trypsin (hereinafter referred to as ".alpha. 1-AT") has been well known as one of the elastase inhibitory proteins which modulate the activity of elastase in the living body. .alpha. 1-AT exists in blood in a large amount and plays a role in inhibiting and neutralizing elastase activity [Nature, 298:329-334 (1982)]. However, since .alpha. 1-AT is very susceptible to oxidization, when air containing high levels of peroxide owing to smoking and air pollution is inhaled continuously, .alpha. 1-AT is oxidized by the inhaled peroxide in the lung, and the elastase inhibitory activity thereof may be lost [Am. Rev. Respir. Dis., 116:65-72 (1977)].
Further, .alpha. 1-AT is oxidized by oxygen released from leukocytes which migrate to the portion in the lung inflamed by the inhalation of the polluted air containing inflammable materials, and it loses elastase inhibitory activity [J. Clin. Invest., 66:987-995 (1980)]. Such inactivation of .alpha. 1-AT leads to a condition of an excess elastase activity in the limited portion in the lung, then the alveolus tissue is degraded by the excess elastase, and results in lung diseases such as pulmonary emphysema [Area of Chemical Therapy, 5:1455-1459 (1989)]. When bacteria infect the lung, and inflammation is therefore caused at the limited portion in the lung, .alpha. 1-AT is also inactivated and the lung tissue may be destroyed because leukocytes such as neutrophil migrate to the inflammatory site by the infection and they secrete a large amount of active oxygen and elastase [Metabolism, 29:41-49 (1992)].
In order to prevent and treat the diseases involving an elastase aforementioned, it has been said that administration of an elastase inhibitory substance such as .alpha. 1-AT into blood or tissue changed pathologically may be effective [Can. Med. Assoc. J., 146:841-844 (1992)]. However, it is necessary to use the .alpha. 1-AT derived from human to avoid an antigen-antibody reaction as a side-effect. Therefore obtaining enough .alpha. 1-AT for prevention and treatment has been difficult.
In addition, since pathogenic virus derived from human may remain in the purified .alpha. 1-AT products, when an elastase inhibitory substance such as.alpha. 1-AT is extracted and purified from human blood, this is a factor that has presented difficulties in using .a
REFERENCES:
patent: 5409895 (1995-04-01), Morishita et al.
patent: 5451659 (1995-09-01), Morishita et al.
Morii et al. (1985) Biol. Chem. Hoppe-Seyler 366: 19-21.
Barrett, Alan J., "The Possible Role of Neutrophil Proteinases in Damage to Articular Cartilage", Agents and Actions, 8:11-18 (1978).
Carp et al., "Potentail Mediator of Inflammation: Phagocyte-Derived Oxidants Suppress the Elastase-Inhibitory Capacity of Alpha.sub.1 -Proteinase Inhibitor in Vitro", J. Clin. Invest., 66:987-995 (1980).
Carrell et al., "Structure and Variation of Human .alpha..sub.1 -Antitrypsin", Nature, 298:329-334 (1982).
Ford et al., "Current Status of Alpha-1-Antitrypsin Replacement Therapy: Recommendations For the Management of Patients With Severe Hereditary Deficiency", Can. Med. Assoc. J., 146:841-844 (1992).
Janoff et al., "Possible Mechanisms of Emphysema in Smokers", Am. Rev. Respir. Dis., 116:65-72 (1977).
Janoff, Aaron Ph.D., "Elastase In Tissue Injury", Ann. Rev. Med., 36:207-216 (1985).
Laemmli, U. K., "Cleavage of Structural Proteins During the Assembly of the Head of Bacteriophage T4", Nature, 227:680-685 (1970).
Ohnishi et al., "Protective Effects of Urinary Trypsin Inhibitor in Experimental Shock", Jpn. J. Pharmacol., 39:137-144 (1985).
Ohnishi et al., "Pharmacological activities of a trypsin inhibitor, urinastatin", Oyo Yakuri, 31(3):663-675 (1986).
Sanger et al., "DNA Sequencing With Chain-Terminating Inhibitors", Proc. Natl. Acad. Sci. (USA), 74:5463-5467 (1977).
Wachter et al., "Kunitz-Type Proteinase Inhibitors Derived by Limited Proteolysis of the Inter-.alpha.-Trypsin Inhibitor, IV.sup.[1-3 ]: The Amino Acid Sequence of the Human Urinary Trypsin Inhibitor Isolated by Affinity Chromatography", Hoppe-Seyler's Z. Physiol. Che,. Bd,. 362:1351-1355 (1981).
Area of Chemical Therapy, 5:1455-1459 (1989).
Bulletin of Pharmacological Society of Japan, 99:93-107 (1992).
Megabolism, 29/1:41-49 (1992).
Genetic-Engineering Handbook:19-26, Yodo-sha eds., (1991).
Kono Yoshio
Mabuchi Toshiyuki
Nakano Shigeru
Nishimura Kaoru
Okushima Minoru
Hobbs Lisa J.
Nissin Shokuhin Kabushiki Kaisha
Wax Robert A.
LandOfFree
Peptide having elastase inhibitory activity and producing method does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Peptide having elastase inhibitory activity and producing method, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Peptide having elastase inhibitory activity and producing method will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1659669