Antibiotic peptides from bovine milk

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai

Reexamination Certificate

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Details

C514S002600, C514S013800, C530S300000, C530S350000, C530S324000, C530S326000, C530S360000, C530S361000, C435S213000

Reexamination Certificate

active

06579849

ABSTRACT:

The present invention is concerned with peptides having the amino acid according to claim
1
, fragments of the peptides obtainable by proteolytic cleavage, a medicament comprising a peptide of the invention, a process for the manufacturing of peptides of the invention, a method of treating by ad-ministering a peptide of the invention as well as methods of using the peptides of the invention.
Antimicrobial peptides are small peptide compounds which are capable to decrease the incidence of disease and could serve as modulators of a naturally occurring bacterial flora (Ganz T. et al., 1992, Med. Microbiol. Immunol. 181, 99-105; Eisenhauer P. B. et al., 1992, Infect. Immun. 60, 3556-3565; Oulette A. J. et al., 1992, FEBS Lett. 304, 146-148; Jones D. E. and Bevins C. L., 1993, FEBS Lett. 315, 187-192; Selstedt M. E. et al. (1992) J. Cell. Biol. 118, 929-936).
The fact that milk could influence micro-organisms is also well established (Wharton B. A. et al, 1994, Acta Paediatr. Jpn. 36, 579-584). Present factors thought to be responsible are lactoferrin (Bullen J. J. et al., 1972, Brit. J. Med. 1, 69-72; Baggiolini M. et al, 1970, J. Exp. Med. 13, 559-570), lysozyme (Fleming A., 1922, Proc. Roy. Soc., London, 93, 306-317, Jolles J. and Jolles P., 1968, Bull. Soc. Chim. Biol., Paris, 50, 2543-2551), lactoperoxidase (Cals M. M. et al., 1991, Eur. J. Biochem. 198, 733-739, Bullen J. J. et al., 1972, Brit. J. Med. 1, 69-72). Milk is a rich source of peptides mainly derived from proteolytic cleavage of proteins. Beyond a nutritive value several biological effects were described like immunomodulation, antithrombotic activities, opioid action or inhibition or mineral carriage (Meisel H. et al., 1989, Z. Ernährungswiss. 28, 267-278; Fiat A. M. and Jolles P., 1989, Mol. Cell. Biochem. 87, 5-30; Fiat A. M. et al., 1993, J. Dairy. Sci. 76, 301-310).
Casocidin-I is a peptide compound, a defined cleavage product from casein-alpha-s2, which is naturally occurring in bovine milk as it could be purified in authentic form (Zucht H. D., 1995, FEBS Lett. 372, 185-188). It has no counterpart in human milk since human milk does not contain any casein of the alpha-s2 type.
Surprisingly, the mild antibacterial effect found in milk could be enriched several orders of magnitude by the peptides of the invention. According to the invention a peptide with antibiotic effects show the amino acid sequence
H
2
N—X
1
—R—X
2
—COOH  (formula I)
wherein
X
1
is either zero or
X
1
and/or X
2
are a residue representing at least five amino acid residues (symbolized in the one letter amino acid code) preferably naturally occurring amino acids,
with the proviso that
X
1
and/or X
2
contain at least one basic amino acid residue immediately followed by a hydrophobic amino acid residue and
X
1
and/or X
2
contain at least one glutamine residue.
Preferably, the distance of the hydrophobic residue and R should not exceed 7-10 amino acids.


REFERENCES:
patent: 44 44 753 (1996-06-01), None
Brignon et al., “Complete Amino Acid Sequence of Bovine &agr;S2-Casein” FEBS Letters, vol. 76(2), pp. 274-279, 1977.*
Brignon et al., “Premiers Elements De Structure Primaire Des Casines &agr;S2Bovines” FEBS Letters, vol. 71(1), pp. 111-116, 1976.*
Zucht et al, Casocidin-I: A Casein &agr;S2Derived Peptide Exhibits Antibacterial Activity FEBS Letters vol. 372, pp. 185-188, Sep. 1995.*
Zucht et al.,FEBS Letters, “Casocidin-I: a casein-&agr;S2derives peptide exhibits antibacterial activity”, pp. 185-188, 1995.
Zucht et al.,The FASEB Journal, Abstracts, Experimental Biology 96™, Washington, D.C., 1996.
Chemical Abstracts, vol. 124, No. 3, Jan. 15, 1996.

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