Cellpep Pharma Inc.

L'oreal

Ambrilia Biopharma, Inc.

Immunosearch

Gellpep S.a.

Centre National De La Recherche Scientifique

Jean-Marc Sabatier

Kamel Mabrouk

Herve Rochat

Jurphaas Van Rietschoten

Zhi Pan

Hervé Groux

Mohammed El-Ayeb

Hervé Rochat

Stephanie Mouhat

Bonabes Olivier De Rouge

Riad Kharrat

Stéphanie Mouhat

Michel Cea-Inserm-Emi9931 LabCanaux Ion Et Signalisation De Waard

A tetrapeptide having antioxidant activity is provided. The tetrapeptide has a structure comprising, in amino acid sequence from N-terminus to C-terminus: tryptophan-X-tyrosine-X; wherein X is arginine, lysine, histidine or any positively-charged amino acid derivative such as 5-hydroxylysine, ornithine, 2,4-diamino-butyrate and 2,3-diamino-propionate. Each amino acid of the sequence or its Homo-amino acid derivative is independently of the D configuration (D-stereoisomer) or of the L configuration (L-stereoisomer), and the C-terminal comprises one selected from the group consisting of carboxyl (&#x2014;COOH), and carboxamide (&#x2014;CONH). A composition stabilized to oxidation or having antioxidant activity and a method for attenuating effects of free radicals on a keratinous material are also provided.

Tetrapeptides and a method of use as an antioxidant

The invention relates to novel polypeptides and to the use thereof for the in vitro assessment of the sensitizing potential of a test compound, to a method for the in vitro assessment of the sensitizing potential of a test compound, to an in vitro method for selecting a compound suitable for reducing the sensitization, as well as to kits for implementing such methods.

Polypeptides for the in vitro assessment of the sensitising potential of a test compound

Derivatives of Maurotoxin (MTX) in which the native disulfide bridge pattern (Cys3-Cys24, Cys9-Cys29, Cys19, Cys31-Cys34) has been disrupted are useful for the treatment of pathologies associated with dysfunctioning and/or activation of Ca-activated and/or voltage-gated Kchannel subtypes, such as IKCa1 or Kv1.2. In one group of derivatives, one or two of the amino acid residues of maurotoxin have been replaced by different amino acid residues resulting in the disulfide bridge pattern being changed to Cys3-Cys24, Cys9-Cys29, Cys13-Cys31, Cys19-Cys34. Exemplary substitutions include the Arg residue at position 14 and/or the Lys residue at position 15 replaced by a Gln residue and the Gly residue at position 33 replaced by an Ala residue. Pi1 and HsTx1 derivatives with disrupted native disulfide bridge patterns are similarly useful.

Maurotoxin, PI1 and HSTX1 derivatives

OsK1 is a 38-residue peptide with 3 disulphide bridges and is found in the venom of the scorpion. It is potently active on voltage-gated Kchannels Kv1.1, Kv1.2 and Kv1.3, and moderately active on the type 1 intermediate-conductance Cat-activated channel K3.1. Derivatives of OsK1, particularly involving truncation or point mutations, have been developed to enhance the activity against and selectivity for the Kv1.3 channel. This renders the derivatives likely candidates for the treatment of autoimmune diseases, including multiple sclerosis. Such use may be alone or in combination therapy with maurotoxin, another scorpion toxin.

OsK1 derivatives

Maurocalcine, a novel toxin isolated from the venom of the Tunisian chactidae scorpion, has the amino acid sequence GDCLPHLKLCKENKDCCSKKCKRRGTNIEKRCR (SEQ. ID. No. 1). It potently and reversibly modifies channel gating behaviour of type 1 ryanodine receptor (RyR1) by inducing prominent subconductance behavior. Maurocalcine and its bioactive structural analogues&#x2014;preferably those containing the KKCKRR motif corresponding to part of the II-III loop of the alpha1S subunit of the voltage-dependent skeletal muscle calcium channel dihydropyridine receptor&#x2014;appear to possess a therapeutic potential, notably as candidate immuno-suppressive drugs, and for the treatment of pathologies in humans that may involve a dysfunction of calcium channels.

Maurocalcine, analogues thereof and their therapeutical uses

Multiple branch peptide constructions formed from peptide-branches derived from the envelope transmembrane glycoprotein gp41 of HIV, and including the consensus sequence RQGY preceded by 0 to 4 amino acid residues and succeeded by 0 to 4 amino acid residues, most preferably RQGYS, show increased receptor affinity and prevent cell-to-cell fusion. They have a direct virostatic effect. Because they present the same peptide sequence several times, these MBPCs are able to neutralize in vitro the different steps of virus envelope/cell membrane fusion, and infected cell membrane/uninfected cell membrane fusion of several strains of HIV-1 and HIV-2. These results open a potential use in treatment of HIV infection.

Multiple branch peptide construction

Multiple branch peptide constructions formed from peptides derived from the envelope transmembrane glycoprotein gp41 of HIV, and including the consensus sequence RQGY preceded by 0 to 4 amino acid residues and succeeded by 2 to 4 amino acid residues, most preferably RQGYSPL, show increased receptor affinity and prevent cell-to-cell fusion. They have a direct virostatic effect. Because they present the same peptide sequence several times, these MBPCs are able to neutralize in vitro the different steps of virus envelope/cell membrane fusion, and infected cell membrane/uninfected cell membrane fusion of several strains of HIV-1 and HIV-2. These results open a potential use in treatment of HIV infection.

Growing community of inventors

Rousset, France

Jean-Marc Sabatier