Yeda Research and Develpment & Co. Ltd

Yechiel Shai

Abraham Patchornik

Shimeon Pass

Dorit Avrahami

Ziv Oren

Avner Fink

Irun R Cohen

Zelig Eshhar

Tova Waks

Yosef Rosenfeld

Shay Yaari

Christopher J Arnush

Eliran-Moshe Reuven

Liraz Shmuel-Galia

Tomer Cohen

Christopher J Arnusch

Neta Sal-Man

Peptides are provided that are capable of inhibiting cell activation mediated by a Toll-like receptor (TLR) selected from TLR 1, 2, 4 or 6, said peptide comprising a sequence consisting of, or found within, the sequence of the transmembrane domain of a TLR selected from TLR 1, 2, 4 or 6 and optionally cytoplasmic and extracellular regions flanking the transmembrane domain. These peptides as well as pharmaceutical composition comprising them are useful for the treatment of TLR-mediated disease.

Peptides based on the transmembrane domain of a toll-like receptor (TLR) for treatment of TLR-mediated diseases

Isolated peptides of 13-30 amino acids comprising 5-9 consecutive repeats of the amino acid pair Alanine-Leucine or Alanine-Valine are provided. The peptides further comprise a stretch of 1-3 Lysine residues present at least at one of the peptide's termini, wherein the only Lysine residue in the isolated peptide is present at the stretch of 1-3 Lysine residues. Pharmaceutical compositions comprising same, methods of treating inflammatory conditions and allergic reactions, as well as methods of neutralizing the activity of lypopolysaccharides are also provided.

Anti-inflammatory peptides and use thereof

The present invention relates to peptides, derivatives and analogs comprising an amino acid sequence derived from the transmembrane domain of HIV gp41 protein, pharmaceutical compositions comprising same, and uses thereof for therapy of inflammatory diseases and disorders, such as T-cell and/or monocyte mediated diseases.

Peptides derived from HIV-1 gp41 transmembrane domain for t-immunomodulation

The invention provides lipophilic conjugates comprising a peptide coupled to a fatty acid, the peptide comprising at least two positively charged amino acid residues, said peptide after conjugation to the fatty acid possessing antibacterial, antifungal, and/or anticancer activity higher than prior to conjugation. The lipophilic conjugates are suitable for treatment of infections caused by pathogenic organisms such as bacteria and fungi. The lipophilic conjugates are also suitable for sanitation, as disinfectants, or for food preservation.

Antimicrobial and anticancer lipopeptides

Lipophilic conjugates comprise a peptide coupled to a fatty acid The peptide comprises at least two positively charged amino acid residues; the peptide after conjugation to the fatty acid possessing antibacterial, antifungal, and/or anticancer activity higher than prior to conjugation. The lipophilic conjugates are suitable for treatment of infections caused by pathogenic organisms such as bacteria and fungi. The lipophilic conjugates are also suitable for sanitation, as disinfectants, or for food preservation.

Non-hemolytic cytolytic agents selected from peptides, complexes of bundled peptides, mixtures of peptides or random peptide copolymers have a selected cytolytic activity manifested in that they have a cytolytic activity on pathogenic cells, being cells which are non-naturally occurring with the body consisting of microbial pathogenic organisms and malignant cells; and are non-hemolytic, having no cytolytic effect on red blood cells. The peptides may be cyclic derivatives of natural peptides such as pardaxin and mellitin and fragments thereof in which L-amino acid residues are replaced by corresponding D-amino acid residues, or are diastereomers of linear peptides composed of varying ratios of at least positively charged amino acid and at least one hydrophobic amino acid, and in which at one of the amino acid residues is a D-amino acid. Pharmaceutical compositions comprising the non-hemolytic cytolytic agents can be used for the treatment of several diseases caused by pathogens including antibacterial, fungal, viral mycoplamsa and protozoan infections and for the treatment of cancer.

Antipathogenic synthetic peptides and compositions comprising them

Peptides which have a net positive charge and none or only a partial a-helix configuration were found to have a non-hemolytic selective cytolytic activity. The peptides may be derived from natural peptides such as pardaxin and mellitin and fragments thereof in which L-amino acid residues are replaced by corresponding D-amino acid residues, and cyclic derivatives of the foregoing, or are diastereomers of linear peptides composed of varying ratios of at least one positively charged amino acid and at least one hydrophobic amino acid, and in which at least one of the amino acid residues is a D-amino acid, and preferably at least one third of the sequence is composed of D-amino acid residues. Pharmaceutical compositions comprising the non-hemolytic cytolytic peptides can be used for the treatment of several diseases caused by pathogens including antibacterial, fungal, viral, mycoplasma and protozoan infections and for the treatment of cancer.

Antipathogenic peptides and compositions comprising them

An automated apparatus for conducting a broad range of organic synthesis reactions includes a first column carring a polymeric support, a second column carrying a second polymer support, and conduits connecting the two columns and permitting the circulation of fluids therebetween. In operation each polymeric support carries a different reactive species and a liquid medium containing a specifically selected intermediate reactant, in a solvent, is circulated between the columns in order to remove the reactive species from the first support by reaction with the intermediate, and to permit the reactive species thus removed to react with the reactive second support, at the same time regenerating the original intermediate reactant. Sensors are placed at the entrance and exit of the second column carrying the second polymeric support. The sensors are capable of sensing the relative presence of the intermediate reactant. When the same content of intermediate reactant is sensed at both the entrance and exit of the second column, the computer causes the circulation to be automatically stopped as this indicates complete loading of the second column.

Apparatus for multipolymer synthesis of organic compounds

A broad range of organic synthesis reactions can be conducted by means of a process using two polymeric supports, each carrying different reactive species. A liquid medium containing a specifically selected intermediate reactant, in a solvent, is circulated between the supports in order to remove the reactive species from the first support by reaction with the intermediate, and permit the reactive species thus removed to react with the reactive species of the second support, at the same time regenerating the original intermediate reactant. This circulation continues until the second support is suitably loaded with the reaction product, at which time the circulation is stopped and the reaction products separated and recovered. The process may be carried out in an automated apparatus in which sensors are placed at the entrance and exit of the column carrying the second polymeric support. The sensors are capable of sensing the relative presence of the intermediate reactant. When the same content of intermediate reactant is sensed at both the entrance and exit of the second column, the circulation will be automatically stopped as this will indicate complete loading of the second column.

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Yahud, Israel

Yechiel Shai