University of California

Synporin Technologies, Inc.

Other

Mauricio Montal

Richard Allen Houghten

Sylvie E Blondelle

Antonio Ferrer-Montiel

John Tomich

Kwok-Keung Tai

Jaume M Canaves

Jaime Merino

Antonio V Ferrer-Monteil

Neuroprotectant agents are provided which do not contain peptides and axe protected from the degradation that limits the use of peptide-based drugs in systemic circulation. With great selectivity for NMDA receptors, the agents exert an open channel block on NMDA receptors, and protect neuronal cells containing such receptors from excitatoxic cell death.

NMDA receptor channel blocker with neuroprotective activity

Compounds that provide protection against excitotoxic neuronal damage are selected from the group consisting of Arg-rich oligopeptides and compounds of formula 1:

N-methyl-d-aspartate receptor channel blockers and method for identifying such

The invention consists of peptides which inhibit the secretion of neurotransmitters from synaptic vesicles. The peptides of the invention are believed to mimic the activity of neurotoxins produced by,and,(including botulinum serotypes A, B, C, D, E, F and G). Structurally, the peptides are comprised of amino acid fragments from the substrate binding domains selected from three proteins which bind to form a receptor for docking of synaptic vesicles to the plasma membranes of neuronal cells; i.e., SNAP-25, VAMP-2 and syntaxin. Certain of the inventive peptides exhibit strong inhibitory activity; e.g., 50% or greater decline in neurotransmitter release is obtained at even nanomolar concentrations. The peptides are suited for use as substitutes for Clostridium neurotoxins in clinical applications and in compounds for targeted delivery of drugs into neural cells.

Peptide inhibitors of neurotransmitter secretion by neuronal cells

The invention consists of modified Clostridium neurotoxin compounds, pharmaceutical compositions containing such compounds and methods for preparing such compounds. In particular, the compounds of the invention are purified Clostridium botulinum and Clostridium tetani neurotoxins in which the tyrosine residues have been modified to have a negative charge (e.g., by covalent attachment of a phosphate or sulphate thereto) or in which the tyrosine residues have been substituted with amino acids having a negative charge (e.g., glutamate, aspartate, or negatively charged, non-natural amino acids). Toxins having phosphorylated tyrosine residues in both the light and heavy chains of the toxins are preferred. Methods for enzymatic and chemical modification of tyrosine residues in purified Clostridium neurotoxins are provided.

Chemically-modified clostridiatoxin with improved properties

The invention relates to synthetic proteins that can be used in in vitro sensing devices to detect the presence of physiologically active substances. The synthetic proteins are mimetic to native ion channels in mammalian systems. The invention also relates to a biosensor comprising a support assembly, a synthetic lipid bilayer containing the active channel protein. Lastly, the invention relates to the use of the biosensor disclosed in the application for the in vitro detection of physiologically active substances including antiseptics, antibiotics, neurotransmittors, and others.

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La Jolla, CA, United States of America

Mauricio Montal