Abstract: Novel synthetic lytic and proliferative peptides were designed and constructed to encompass the structural features associated with lytic and proliferative activity. These compounds, along with the human &bgr; fibrin signal peptide share structural and functional properties of the known lytic peptides. These peptides are effective agents in the treatment of microbial infections including gram negative and gram positive bacteria, fungus, virus, yeast, and protozoa, in the lysis of cancer cells, and in the proliferation of fibroblasts and lymphocytes. Additional functions include synergy and use as general adjuvants and in the enhancement of wound healing.

Abstract: A novel class of antimicrobial agents for animal species including cecropins, attacins, lysozymes, phage derived polypeptides, such as those transcribed from gene 13 of phage 22, an S protein from lambda phage, and an E protein from phage PhiXl74, as well as, synthetically derived polypeptides of similar nature. The antimicrobial agents can be used to treat microbial infections and as components of medicinal compositions. The genes encoding for such antimicrobial agents can be used to transform animal cells, especially embryonic cells. The transformed animals including such antimicrobial cells are also included.

Abstract: Novel synthetic lytic and proliferative peptides were designed and constructed to encompass the structural features associated with lytic and proliferative activity. These compounds, along with the human &bgr; fibrin signal peptide share structural and functional properties of the known lytic peptides. These peptides are effective agents in the treatment of microbial infections including gram negative and gram positive bacteria, fungus, virus, yeast, and protozoa, in the lysis of cancer cells, and in the proliferation of fibroblasts and lymphocytes. Additional functions include synergy and use as general adjuvants and in the enhancement of wound healing.

Abstract: A method of treating a wound of a mammalian subject in rneed of such treatment, to promote healing thereof, comprising administering to the subject, e.g., to the wound locus, a composition comprising a fibroblast and keratinocyte proliferatingly effective amount of an amphipathic peptide, preferably an amphipathic peptide which is antimicrobially effective at such locus. A method is also disclosed of stimulating the accelerated growth of dermal tissue in a tissue culture containing same, comprising applying to the tissue culture a fibroblast and keratinocyte proliferatingly effective amount of an amphipathic peptide, by which the dermal tissue may be grown to produce skin for skin grafting purposes, utilizing a dermal tissue culture containing dermal tissue material of a skin graft recipient of such skin. Novel amphipathic peptides suitable for use in such methods are disclosed.

Abstract: A method of treating a wound of a mammalian subject in need of such treatment, to promote healing thereof, comprising administering to the subject, e.g., to the wound locus, a composition comprising a fibroblast and keratinocyte proliferatingly effective amount of an amphipathic peptide, preferably an amphipathic peptide which is antimicrobially effective at such locus. A method is also disclosed of stimulating the accelerated growth of dermal tissue in a tissue culture containing same, comprising applying to the tissue culture a fibroblast and keratinocyte proliferatingly effective amount of an amphipathic peptide, by which the dermal tissue may be grown to produce skin for skin grafting purposes, utilizing a dermal tissue culture containing dermal tissue material of a skin graft recipient of such skin. Novel amphipathic peptides suitable for use in such methods are disclosed.

Abstract: A non-neurotoxin, arginine residue-containing non-naturally occurring lytic peptide comprising a sequence of amino acid residues in sufficient number and arrangement to confer lytic activity to the peptide, wherein the guanido groups of the arginine residues and the .alpha.-amino group of the N-terminal amino acid are sufficiently glyoxylated to impart enhanced tryptic, chymotryptic, and aminopeptidase digestion resistance to the peptide. The compositions of the invention are suitable for in vivo administration. A method of-making the same, to impart enhanced tryptic digestion resistance thereto, comprising glyoxylating the guanido groups of the arginine residues and the .alpha.-- amino group of the N-terminal amino acid with glyoxa containing buffer for sufficient time and at sufficient conditions to glyoxylate the side chain and .alpha.-amino groups to sufficient extent to confer enhanced proteolytic digestion resistance to the peptide.

Abstract: Inhibition of eucaryotic pathogens and neoplasms and stimulation of lymphocytes and fibroblasts with lytic peptides such as cecropins and sarcotoxins. Eucaryotic cells are contacted with cecropin or sarcotoxin, or a synergistic combination of cecropins or sarcotoxin with lysozyme, in an amount effective to lyse or inhibit the cells. Target cells include eucaryotic microorganisms such as protozoa, e.g. T. cruzi and P. falciparum, mammalian lymphomas and leukemias, and cells infected with intracellular pathogens such as viruses, bacteria and protozoa. Also disclosed is a method for stimulating proliferation of lymphocytes and fibroblasts by contacting such cells with an effective amount of cecropin or sarcotoxin. The methods may be in vitro or in vivo.

Abstract: Novel synthetic lytic and proliferative peptides were designed and constructed to encompass the structural features associated with lytic and proliferative activity. These compounds, along with the human .beta. fibrin signal peptide share structural and functional properties of the known lytic peptides. These peptides are effective agents in the treatment of microbial infections including gram negative and gram positive bacteria, fungus, virus, yeast, and protozoa, in the lysis of cancer cells, and in the proliferation of fibroblasts and lymphocytes. Additional functions include synergy and use as general adjuvants and in the enhancement of wound healing.

Abstract: Plant transformants having an expressible heterologous gene for an antimicrobial agent for disease resistance and/or a protein high in limiting essential amino acid content for enhanced nutritional quality. Monocots, dicots and gymnosperms are genetically enhanced for disease resistance to express a lytic peptide such as cecropin, attacin or lysozyme, or an antiviral antisense micRNA. The nutritional quality of plants cultivated for food is enhanced by a gene expressing a protein containing 25-60 weight percent of methionine, lysine, tryptophan, threonine and isoleucine. Methods for obtaining such transformants, novel expressing vectors, novel proteins high in essential amino acids, and novel lytic peptides are also disclosed.

Abstract: A method of treating neoplasias, including female mammalian neoplasias such as breast, cervical, uterine, and ovarian neoplasias, as well as other neoplasias including prostatic, dermal, and bronchogenic cancers, comprising delivery of an effective non-naturally occurring, non-cytologically proliferative lytic peptide to an appropriate corporeal site to effectively treat such disease state. Particlularly preferred lytic peptide agents include small (23-39 amino acids) amphipathic cationic lytic peptides from the classes of synthetic analog derivatives of mellittin, cecropin, magainin, and defensin peptides, most preferably melittic and defensin peptides from the class of synthetic analogs of melittin, cecropin, maganin, and defensin peptides, most preferably synthetic analogs of melittic and defensin peptides.

Abstract: A method of treating pulmonary disease states, e.g., a disease state selected from the group consisting of: cystic fibrosis, neoplasias, bronchogenic cancers, pneumonia, bronchitis, bronchopulmonary viral infections, and bronchopulmonary microbial infections, comprising delivery of an amphipathic non-naturally occurring peptide to an appropriate corporeal site, e.g., pulmonary and/or gastrointestinal loci, to effectively treat such diseases. In a further specific aspect, the invention contemplates a method of treating cystic fibrosis by delivery of lytic, amphipathic non-naturally occurring peptides to pulmonary loci, thereby effecting treatment of bronchopulmonary microbial infections associated with cystic fibrosis through lysis of pathogenic bacteria. Peptides delivered to a gastrointestinal locus preferably are non-lytic, so as not to affect normal gastrointestinal flora, and preferably are chemically modified to confer enhanced proteolytic resistance for an oral method of delivery.

Abstract: A tryptic digestion-resistant, non-naturally occurring lytic peptide comprising a sequence of amino acid residues containing mainly alanine, valine and lysine amino acid residues, wherein the .epsilon.-amino groups of the lysine residues and the .alpha.-amino group of the N-terminal amino acid are sufficiently methylated to impart enhanced tryptic, chymotryptic, and aminopeptidase digestion resistance to the peptide. The secondary conformation of the peptide is an ordered periodic structure such as an amphipathic .alpha.-helix or a .beta.-pleated sheet. The compositions of the invention are suitable for in vivo administration.A method of making the same, to impart enhanced tryptic digestion-resistance thereto, comprising reductively alkylating the .epsilon.-amino groups of the lysine residues and the .alpha.-amino group of the N-terminal amino acid with a methyl-providing reagent in the presence of an heterocyclic amine-borane reducing agent for sufficient time and at sufficient conditions to methylate the .

Abstract: A method of inhibiting pathogenic conditions of plants including viral, bacterial, and fungal infections and insert infestations by expressing into the plant genome genes encoding for a polypeptide inhibitor or inhibitor precursor of the pathogenic condition which inhibitor or precursor is selected from complementary oligonucleotides for blocking viral transcription or translation produced in vivo, one or more proteins derived from the humoral response to bacterial infection of the Hyalophora, an antifungal plasmid or a chitin integument disruption chitinase enzyme. Novel microbes, polypetides, and compositions containing amino acid sequences are disclosed.

Abstract: Plant transformants having an expressible heterologous gene for an antimicrobial agent for disease resistance and/or a protein high in limiting essential amino acid content for enhanced nutritional quality. Monocots, dicots and gymnosperms are genetically enhanced for disease resistance to express a lytic peptide such as cecropin, attacin or lysozyme, or an antiviral antisense micRNA. The nutritional quality of plants cultivated for food is enhanced by a gene expressing a protein containing 25-60 weight percent of methionine, lysine, tryptophan, threonine and isoleucine. Methods for obtaining such transformants, novel expressing vectors, novel proteins high in essential amino acids, and novel lytic peptides are also disclosed.

Abstract: A method of treating a wound of a mammalian subject in need of such treatment, to promote healing thereof, comprising administering to the subject, e.g., to the wound locus, a composition comprising a fibroblast and keratinocyte proliferatingly effective amount of an amphipathic peptide, preferably an amphipathic peptide which is antimicrobially effective at such locus. A method is also disclosed of stimulating the accelerated growth of dermal tissue in a tissue culture containing same, comprising applying to the tissue culture a fibroblast and keratinocyte proliferatingly effective amount of an amphipathic peptide, by which the dermal tissue may be grown to produce skin for skin grafting purposes, utilizing a dermal tissue culture containing dermal tissue material of a skin graft recipient of such skin. Novel amphipathic peptides suitable for use in such methods are disclosed.

Abstract: A process for cloning the chitinase gene of Vibrio parahemolyticus is provided, comprising the steps of cleaving the Vibrio parahemolyticus DNA with Sau3A, PSTI or other restriction enzyme, mixing the cleaved DNA fragments in the presence of pUC18 and T4 ligase to produce a composite plasmid, and inserting the composite plasmid in a DH5a strain of E. Coli.

Abstract: A novel agriculturally useful composition that includes a seed treated with selected infectivity-cured Hr plasmid-bearing microorganism. Also provided are methods of enhancing root elongation, shoot elongation or root development of selected seeds. These methods include treating a selected seed with the infectivity-cured Hr plasmid-bearing microorganism. In addition, there is provided a method of inducing germination of grass seed that involves treating a grass seed such as Kentucky bluegrass seed with a selected infectivity-cured Hr plasmid-bearing microorganism. Furthermore, there is provided a method of promoting plant growth at a lower soil temperature than is common at the time of planting a seed of the plant. Additionally, there is disclosed an inoculant for increasing nodulation, root mass and shoot mass in a leguminous plant. The inoculant contains a Rhizobium microorganism and a selected infectivity-cured Hr plasmid-bearing microorganism.

Abstract: A novel agriculturally useful composition that includes a seed treated with a selected infectivity-cured Hr plasmid-bearing microorganism. Also provided are methods of enhancing root elongation, shoot elongation or root development of selected seeds. These methods include treating a selected seed with the infectivity-cured Hr plasmid-bearing microorganism. In addition, there is provided a method of inducing germination of Kentucky bluegrass seed that involves treating Kentucky bluegrass seed with a selected infectivity-cured Hr plasmid-bearing microorganism. Furthermore, there is provided a method of promoting plant growth at a lower soil temperature than is common at the time of planting a seed of the plant. Additionally, there is disclosed an inoculant for increasing nodulation, root mass and shoot mass in a leguminous plant. The inoculant contains a Rhizobium microorganism and a selected infectivity-cured Hr plasmid-bearing microorganism.