31results about "Bactericidal/permeability-increasing protein" patented technology

The invention provides cell penetrating peptide-nucleic acid conjugates having the formula P-L-N, wherein P is a cell penetrating peptide, N is a nucleic acid, preferably an oligonucleotide and more preferably a siRNA, and L is a hydrophilic polymer, preferably a polyethylene glycol (PEG)-based linker linking P and N together. Compositions, methods of use and methods for producing such conjugates are also disclosed.

The antimicrobial activity of bovine bactericidal / permeability-increasing protein (bBPI)-derived synthetic peptides against mastitis-causing Gram-negative bacteria was evaluated. Three peptides were synthesized with sequences corresponding to amino acids 65-99 (bBPI65-99), 142-169 (bBPI142-169), or the combination of amino acids 90-99 and 148-161 (bBPI90-99,148-161) of bBPI. The bBPI90-99,148-161 peptide demonstrated the widest spectrum of antimicrobial activity, with minimum inhibitory (MIC) and bactericidal (MBC) concentration values ranging from 16-64 μg / ml against Escherichia coli, Klebsiella pneumoniae, and Enterobacter spp, and 64-128 μg / ml against Pseudomonas aeruginosa. None of the peptides exhibited any growth inhibitory effect on Serratia marcescens. The antimicrobial activity of bBPI90-99,148-161 was inhibited in milk, but preserved in serum. Finally, both bBPI142-169 and bBPI90-99,148-161 were demonstrated to completely neutralize LPS. The peptide bBPI90-99,148-161 is a potent neutralizer of the highly pro-inflammatory molecule bacterial LPS and has antimicrobial activity against a variety of Gram-negative bacteria.

A peptide with an amino acid composition such that the peptide is amphipathic, cationic and forms a stable alpha-helix and has the following structure comprising at least 12 amino acidsA=an amino acid selected from the basic amino acids Lys,Arg or HisB=an amino acid selected from the aromatic amino acids Phe, Trp or TyrC=an amino acid selected from the group comprising the hydrophobic amino acids Leu, Ile, Val or Ala, andsaid peptide has either the orientation according to the formula or the retro orientation thereof, wherein at least 0-m of the repetitive sequence motifs (A2-B2-C1-A3) have the retro orientation and the remaining repetitive motifs (A2-B2-C1-A3) have the orientation as presented in the formula and wherein,R1-R2- and R3 are a number of amino acids, and whereinm=1-10, preferably 2-8, more preferably 2-5 andn=1-3, a pharmaceutical composition comprising such a peptide application thereof in treatment or diagnosis related to i.a. parasite infection topical and systemic tumors and septic shock.

The present invention is directed to compositions and methods for the treatment of diseases comprising the administration of compositions comprising one or more peptide(s) having a stimulatory effect on the afflicted host's immune system. Specifically, the invention relates to methods comprising the use of cationic amphipathic peptides having an alpha-helical structure and effecting activation of macrophages when administered in a therapeutically sufficient amount. The methods of the present invention are useful for the treatment of, for example, infectious diseases or cancer.

Soluble variants of recombinant proteins produced in a prokaryotic host cell, where the high expression levels often cause the original proteins to aggregate into insoluble inclusion body aggregates. The variant polypeptides retain biological function while increasing protein solubility with comparable or higher recoverable levels of biologically active protein when expressed in a suitable expression host. Methods of identifying critical residues and substituting them are provided to produce the variants.

A method for determining improved disease resistance in animals is disclosed. The method assays for a novel genetic alleles of the BPI gene of the animal. The alleles are correlated with superior disease resistance. Novel nucleotide sequences, assays and primers are disclosed for the methods of the invention.

Therapeutic methods using a purified isolated human bactericidal / permeability-increasing protein and biologically-active fragments thereof is provided.

This invention relates to the chemical design and production of peptides, peptide structure and three dimensional conformation was assessed using NMR, circular dichroisin and pulsed field gradient NMR. In addition, this invention relates to peptides produced by these methods and to methods for using the peptides.

The present invention is directed to compositions and methods for the treatment of diseases comprising the administration of compositions comprising one or more peptide(s) having a stimulatory effect on the afflicted host's immune system. Specifically, the invention relates to methods comprising the use of cationic amphipathic peptides having an alpha-helical structure and effecting activation of macrophages when administered in a therapeutically sufficient amount. The methods of the present invention are useful for the treatment of, for example, infectious or cancer.

A peptide with an amino acid composition such that the peptide is amphipathic, cationic and forms a stable alpha-helix and has the following structure comprising at least 12 amino acids R1-R2-A1-B1-(A2-B2-C1-A3)m-(C2)n-R3, wherein A=an amino acid selected from the basic amino acids Lys,Arg or His B=an amino acid selected from the aromatic amino acids Phe, Trp or Tyr C=an amino acid selected from the group comprising the hydrophobic amino acids Leu, Ile, Val or Ala, and said peptide has either the orientation according to the formula or the retro orientation thereof, wherein at least 0-n of the repetitive sequence motifs (A2-B2-C1-A3) have the retro orientation and the remaining repetitive motifs (A2-B2-C1-A3) have the orientation as presented in the formula and wherein, R1-R2- and R3 are a number of amino acids, and wherein m=1-10, preferably 2-8, more preferably 2-5 and n=1-3, a pharmaceutical composition comprising such a peptide application thereof in treatment or diagnosis related to i.a. parasite infection topical and systemic tumors and septic shock.

This invention relates to the chemical design and production of peptides, peptide structure and three dimensional conformation was assessed using NMR, circular dichroisin and pulsed field gradient NMR.

The present invention relates generally to small peptide-based constructs and their therapeutic uses. The sequences of these peptide-based constructs are based on a reverse subsequence derived from Domain II of bactericidal / permeability-increasing protein (BPI).

The present invention relates generally to anti-fungal peptides derived from or based on Domain III (amino acids 142-169) of bactericidal / permeability-increasing protein (BPI) and therapeutic uses of such peptides.

The present invention solves the three-dimensional structure of BPI and thereby provides atomic coordinates of BPI from the analysis of x-ray diffraction patterns of sufficiently high resolution for three-dimensional structure determination of the protein, as well as methods for rational drug design, based on using amino acid sequence data and / or x-ray diffraction data provided on computer readable media, as analyzed on a computer system having suitable computer algorithms; and atomic coordinates are provided yielding structural information on related proteins, including the lipid binding and lipid transport protein family that includes BPI, LBP, CETP and PLTP.

Bactericidal / permeability increasing protein (BPI) and biologically active fragments, analogs and variants thereof are solubilized by lipid carriers including phospholipids, liposomes and nonionic detergents and stabilized against particle formation by poloxamer surfactants.

The present invention relates to an variant of BPIFB4 (Bactericidal / Permeability Increasing protein family B, member 4) protein and its use for the treatment of pathologies involving impairment of nitric oxide signalling.

The present invention relates to variants of the BPIFB4 (bactericidal / permeability-increasing protein family B, member 4) protein and their use for the treatment of conditions involving impaired nitric oxide signaling.

A purified, isolated DNA sequence encoding human bactericidal / permeability-increasing protein and biologically-active fragments thereof is provided.

The present invention relates to bactericidal / permeability increasing protein (BPI) for use in a method of immunization of a patient, preferably as an adjuvant in a method of vaccination. The present invention also relates to a preparation comprising BPI for use in a method of immunization of a patient, and optionally an immunomodulatory agent. The present invention further relates to a process of producing a preparation including BPI for use in a method of immunization of a patient.

The present invention relates to a novel Diastereo analog Dsam of peptide SPFK-amide of amino acid sequence PKLLKTFLSKWIG with D-Leu residues at positions 4 and 8 of analog, having selective anti-microbial activity and no hemolytic activity of said SPFK, and a method of producing said Diastereo analog.

The present invention discloses a recombinant virus, which comprises a viral vector, and a gene construct selected from the following: 1) a human BPI gene or a functional fragment gene thereof, or a degenerate Sequence thereof, and 2) a chimeric gene comprising a human BPI gene or a functional fragment gene thereof, or a degenerate Sequence thereof, wherein the chimeric gene further comprises a Fc constant region gene or its allelic gene of a heavy chain of a human immunoglobulin in the 3' end of the human BPI gene or the functional fragment gene thereof. This invention also discloses the use of the gene construct comprising the human BPI gene or functional fragment gene thereof in the preparation of the pharmaceutical composition of gene therapy of the GNB and / or GNB like pathogen infection in Mammal. The present invention further provides a gene therapy method of the GNB and / or GNB like pathogen infection using the recombinant virus or the pharmaceutical composition.

Novel BPI deletion analogs are provided that consist of amino acid residues 10 through 193 of mature human BPI wherein the cysteine residue at BPI amino acid position 132 is replaced by another amino acid. Fusion proteins comprising these analogs are also provided, as are polynucleotides encoding these products, materials and methods for their recombinant production, compositions and medicaments of these products, and therapeutic uses for these products.