Synthetic resins or natural rubbers -- part of the class 520 ser – Synthetic resins – Mixing of two or more solid polymers; mixing of solid...
Patent
1995-12-18
1998-12-08
Wax, Robert A.
Synthetic resins or natural rubbers -- part of the class 520 ser
Synthetic resins
Mixing of two or more solid polymers; mixing of solid...
530326, 530300, C08G 6300
Patent
active
058470476
DESCRIPTION:
BRIEF SUMMARY
FIELD OF INVENTION
The invention relates to the design and synthesis of novel antimicrobial compositions comprising unique amino acid sequences that form amphiphilic helices and possess antimicrobial properties. More specifically, the invention provides the peptides of amino acid sequences KGLKKLLKLLKKLLKL,(SEQ ID NO:1) LKLLKKLLKL LKKLGK(SEQ ID NO:2) KGGLKKLLKLLKKLLKL (SEQ ID NO:3), LKLLKKLLKLLKKLGGK (SEQ ID NO:4) and KGGGLKKLLKLLKKLLKL (SEQ ID NO:5) LKLLKKLLKLLKKLGGGK (SEQ ID NO:6) where these peptides have the capability of killing microorganisms without being indiscriminately cytotoxic. The invention further relates to the incorporation of these and other antimicrobial peptides into polymer compositions without limiting the bioactivity of the peptides.
BACKGROUND OF THE INVENTION
Many vertebrates and invertebrates secrete natural substances that possess both antibacterial and/or indiscriminate cytotoxic properties. Examples of some of these substances include PGLa (frog skin), defensins (human phagocytes), cecropins (Silkmoth pupae or pig intestine), apidaecins (honeybee lymph), melittin (bee venom), bombinin (toad skin) and the magainins (frog skin). Purification of the active constituents of these natural substances have shown that they consist primarily of protein and it has been suggested that they may constitute a system of cellular immunity in the producing organism.
Peptides and oligopeptides that have activity against microorganisms span a broad range of molecular weights, secondary conformations and sites of action. Biological activity can range from being specifically bactericidal or fungicidal to being indiscriminately cytotoxic (cell lytic) to all cells. Peptides that are specifically bactericidal include large polypeptides such as lysozyme (MW 15000 daltons) and attacins (MW 20-23,000 daltons) as well as smaller polypeptides such as cecropin (MW 4000 daltons) and the magainins (MW 2500 daltons). The spectrum of biocidal activity of these peptides is somewhat correlated to size. In general, the large polypeptides are active against limited types and species of microorganisms (e.g., lysozyme against only gram positive bacteria), whereas many of the smaller oligopeptides demonstrate a broad spectrum of antimicrobial activity, killing many species of both gram positive and gram negative bacteria.
Although few similarities exist between the amino acid sequences of the biocidal peptides, it has been shown that magainin, cecropins, and bombinin oligopeptides form similar secondary structures described as an amphiphilic helix (Kaiser et al. Annu. Rev. Biophys. Biophys. Chem 16, 561-581, 1987). Amphiphilic or amphipathic helices are secondary protein structures possessing an overall affinity for hydrophillic materials. It has been suggested that the affinity of these helices for cell membranes may account, in part, for their biological activity and the literature would suggest that there may be a strong correlation between this secondary peptide structure and biological activity (Lee et al. Biochem. Biophys. Acta 862, 211-219, (1986)).
One of the first biocidal oligopeptides to be isolated from natural sources was bombinin and is described by Csordas et al. (Proc. Int. Symp. Anim. Plant Toxins, 2, 515-523, (1970)). Bombinin is found in toad skin secretions and has both antimicrobial and cytotoxic properties. Csordas teaches significant sequence homology between bombinin and melittin, another antimicrobial peptide, isolated from bee venom.
DeGrado and Kezdy (J.A.C.S. 103, 679-681,(1981)) describe the preparation of potent synthetic analogues of melittin using rational peptide design. The peptide sequences of DeGrado were shown to have both structural and functional similarities to melittin in that both attained similar amphiphillic helical secondary conformation and both were indiscriminately cytotoxic. Subsequently DeGrado et al. (Peptides: Structure and Function., Proc. 8th Amer. Peptide Symp., V. J. Hruby Ed., (1983)) prepared a series of idealized synthetic oligopeptides to mimic the cecropin
REFERENCES:
patent: 4496363 (1985-01-01), DeFilippi
patent: 4810567 (1989-03-01), Calcaterra et al.
patent: 5008371 (1991-04-01), Natori
patent: 5019093 (1991-05-01), Kaplan et al.
patent: 5073542 (1991-12-01), Zasloff
patent: 5096886 (1992-03-01), Boman et al.
Suenaga (1989) Biochim. Biophys. ACTA, 981, pp. 143-152.
Duran, (1993) Abstracts of the 19th Annual Meeting of the Soc. for Biomaterials, p. 35.
Abstract of WO 89/04371, Mar. 19, 1990.
Goldstein, (1981) J. Chromatog. 215, pp. 31-43.
Lin et al. (1992) J. Biomater. Sci. Polymer Ed. 3/3, pp. 217-227.
Lee et al. (1986) Biochim. Biophys. ACTA, 862, pp. 211-219.
DeGrado (1983) Peptides: Structure and Function, 195-198.
Zasloff (1987) Proc. Natl. Acad. Sci. USA, vol. 84, pp. 5449-5453.
Chen et al. (1988) FEB, vol. 236, pp. 462-466.
Peck-Miller et al. (1993) Cancer Chemother. Pharmacol., vol.32, pp. 109-115.
Jaynes et al. (1990) GenBank database, Accession No. P91350.
Jaynes et al. (1990) GenBank database, Accession No. P91335.
E. I. Du Pont de Nemours and Company
Longton Enrique D.
Wax Robert A.
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