Peptides having immunomodulatory activity

Details Peptides having immunomodulatory activity Peptides having immunomodulatory activity

1997-06-19

1999-11-09

Wortman, Donna

Drug, bio-affecting and body treating compositions

Nonspecific immunoeffector, per se ; or nonspecific...

530330, A61K 3804, A61K 4500

Patent

active

059809132

DESCRIPTION:

BRIEF SUMMARY
FIELD OF THE INVENTION

The present invention relates to peptides having an immunomodulatory activity. In particular, the present invention relates to peptides which stimulate the immune system in animals, including humans. The present invention is concerned with the tetrapeptide H-Lys-Asn-Pro-Tyr-OH (SEQ ID NO:1) and analogues thereof as immunomodulators.
The present invention also includes compositions containing such immunomodulatory peptides and the use of such peptides and compositions as immunomodulators.
The present invention also includes the use of such peptides as a vaccine adjuvant.


BACKGROUND OF THE INVENTION

The primary function of the immune system relates to the protection of the body from disease. The immune system protects against not only those diseases which result from an attack by bacteria, virus, and other pathogens, but also cancer, as well as disease states which result from immune imbalance; opportunistic infections, or autoimmune disorders.
In a number of diseases or other pathological conditions, the immune system response of an animal or human is depressed. As a result, the subject becomes more susceptible to malignancies, or pathological infections against which a normal immune system would have protected the subject. Some conditions which depress the immune system include acquired immune deficiency syndrome (AIDS), chronic infection, chemotherapy, trauma of surgery, and aging.
Modulation of the immune system through pharmaceutically induced stimulation or suppression offers an important approach to the control of disease. Compounds which nonspecifically stimulate the immune system are of potentially significant medicinal importance and have been the object of lengthy research efforts. Often, the research results show that immunomodulating compounds are either weak immunostimulants, and therefore not very effective, or potent immunostimulants and, therefore, effective but toxic by virtue of this potent immunostimulating activity.
Among the many classes of compounds which non-specifically stimulate the immune system are a number of naturally occurring peptides or fragments thereof. One such fragment is Imreg, a tripeptide of the general sequence Tyr-Gly-Gly disclosed in U.S. Pat. No. 4,699,898 issued Oct. 13, 1987. This patent does not disclose the sequence of the peptides of the present invention. Imreg can be isolated from human leukocytes. It is a thymomimetic but possesses weak potency. (A. Arthur Gottlieb, Int.J.Immunopharm.Vol.13, Suppl.1, p.29-32 (1991)).
Another fragment of a naturally occurring peptide is the tetrapeptide Tuftsin and its close analogue Rigin. These peptides have the respective sequences Thr-Lys-Pro-Arg and Gly-Gln-Pro-Arg. Analogues of tuftsin can be found, for example, in Biondi et al., "Synthesis of glycosylated tuftsins and tuftsin-containing IgG fragment undecapeptide", Int.J.Peptide Protein Res. 37, 1991, p.112-121, and Verdini et al., "Immunostimulation by a partially modified retro-inverso-Tuftsin analogue containing Thr.sup.1 .psi.[NHCO](R,S)Lys.sup.2 modification", J.Med.Chem., 1991 34, p.3372-3379. These publications do not disclose peptides with the sequence of the present invention. Tuftsin and rigin are both fragments of IgG and are found within the heavy chain of leukokinin. Tuftsin is a well-known macrophage activator and is known to stimulate NK cell activity. However, it is unstable in plasma which may strongly reduce its stimulating effects on the immune system.
Another fragment of a naturally occurring peptide known to have immunomodulating effects is thymopentin. (Audhya et al., "Contrasting biological activities of thymopoietin and splenin, two closely related polypeptide products of thymus and spleen", Proc.Natl.Acad.Sci.USA, 81,p.2847-2849, 1984; U.S. Pat. No. 5,218,089 issued Jun. 8, 1993; U.S. Pat. No. 5,091,510 issued Feb. 25, 1992). This pentapeptide has the sequence Arg-Lys-Asp-Val-Tyr. Thymopoietin is a 49 amino acid polypeptide thymus hormone. The pentapeptide is the smallest fragment of thymopoietinq which retains the i

REFERENCES:
Matsuda et al., "Manufacture of peptides by hydrolysis of actin-series proteins, and activity as angiotensin 1-converting enzyme inhibitors" Abstract Jpn. Kakai Tottyo Koho, 6 pp. CODEN: JKXXAF.
Birr et al., "Propeptides of proalbumin and their use" Abstract Ger. Offen., 24pp. CODEN: GWXXBX May 5, 1983.
Database WPI, Sect.ch.week 9345, Derwent Pub. ClassB04, AN93-357193.
H. Niedrich, "Synthesis of some tetrapeptide analogs of the eledoisin sequence KDAF" pp.3136.
J. Prakt Chem. vol. 35, No. 3-4, 1967pp.213-224.
I.Z. Siemion E.A., "Suppression of tuftsin activity by the partial sequences of adenovirus type 2 proteins", see pp. 300-306, vol. 41, 1993 International Journal of Peptide and Protein Research.
N.A. Leone E.A. "Characterisation of an epitope", pp. 327-330, vol. 335, No. 3 Dec. 1993, FEBS Letters.
Siemion, et al., "Suppression of tuftsin activity . . . ", Int. J. Peptide Protein Res. 41 (1993), 300-306.
Semni, E., "New angiotensin convert enzyme . . . ", CA 67 (1967), 3136.
Leone, et al., "Characterisation of an epitope recognised . . . ", FEBS 335, 3 (1993), 327-330.

Affiliated with

Also associated with

Rating

Peptides having immunomodulatory activity does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Peptides having immunomodulatory activity, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Peptides having immunomodulatory activity will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-1452069