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Carrier for targeting nerve cells

A technology of nerve cells and neurotoxins, applied in the field of transporters, which can solve the problem of not revealing amino acids and so on

Inactive Publication Date: 2008-05-21
TOXOGEN +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

But the document does not reveal the amino acids associated with the binding pockets of BoNT / B and G

Method used

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  • Carrier for targeting nerve cells
  • Carrier for targeting nerve cells
  • Carrier for targeting nerve cells

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Embodiment Construction

[0076] Specifically, the present invention contains a transporter protein (Trapo), which is formed by modifying the HC of the neurotoxin produced by Clostridium botulinum, and preferably specifically binds to neurons, preferably through receptor-mediated endocytosis Intracellularly taken up and translocated from the acidic endosomal compartment into the neuronal cytoplasm. This protein is used as a transporter to introduce proteases and other substances bound to the transporter and unable to physiologically penetrate the cell membrane and reach the cytoplasmic fluid of nerve cells into cells. The substrates of this protease are proteins and polypeptides localized in cells involved in the release of neurotransmitters. After the substrate is dissociated, specific functions of the neuron are blocked; however, the cell itself is not damaged. One of these functions is exocytosis resulting in the release of neurotransmitters. If transmitter release is inhibited, signaling from cel...

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Abstract

New transport protein (A) obtained by modification of the heavy chain of a neurotoxin produced by Clostridium botulinum. Compared with the native neurotoxin (nNT) it: (a) binds with higher or lower affinity to nerve cells; (b) has higher / lower neurotoxicity, particularly as determined in the hemidiaphragm assay; and / or (c) has lower affinity for neutralizing antibodies. Independent claims are also included for the following: (1) composition (C) comprising (A) and at least one intervening compound; (2) method for producing (A) or (C) by standard recombinant methods; (3) host cells that contain a recombinant expression vector (EV) encoding (A) or (C); and (4) EV. - ACTIVITY : Relaxant; Antimigraine; Analgesic; Vulnerary; Antidepressant; Virucide. No details of tests for these activities are given. - MECHANISM OF ACTION : Delivering agents that inhibit release of neurotransmitters.

Description

technical field [0001] The present invention relates to a transporter that binds to neurons with higher or lower affinity than a neurotoxin formed by Clostridium botulinum. This transporter is preferably taken up by receptor-mediated endocytosis. This protein can be used as a transporter to move other chemicals, such as proteases, which cannot physiologically penetrate the plasma membrane into the neuronal cytoplasm, from the acidic endosomal compartment. In particular, the present invention relates to the use of a transporter for introducing neurotransmitter release inhibitors. Background technique [0002] Nerve cells release transmitters through exocytosis. The fusion of the membrane of the intracellular vesicle with the plasma membrane of the cell is called exocytosis. During this process, the vesicle contents are simultaneously drained into the synaptic cleft. The fusion of the two membranes is regulated by calcium, which reacts with the protein synaptotagmin. Toge...

Claims

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Application Information

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IPC IPC(8): C07K14/195C07K14/33A61K38/00
CPCC07K14/33A61K38/00C12N9/52C12Y304/24069A61P17/02A61P19/00A61P25/00A61P25/04A61P25/06A61P25/24A61P25/26A61P27/02Y02A50/30C07K14/195
Inventor 安德列斯·隆美尔塔尼亚·魏尔亚历山德斯·古特塞茨
Owner TOXOGEN
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