BINDING OF PATHOLOGICAL FORMS OF PROTEINS USING CONJUGATED POLYELECTROLYTES

• US 20100310462A1
• Filed: 06/03/2010
• Published: 12/09/2010
• Est. Priority Date: 04/18/2007
• Status: Abandoned Application

• Current Assignee: BioChromix AB (Rajiv Indravadan Modi, PhD)
• Original Assignee: BioChromix AB (Rajiv Indravadan Modi, PhD)
• Inventors: Anghus, Fredrik, Inganäs, Olle, Åsberg, Peter
• Application Number:
  US12/793,570
• Publication Number:
  US 20100310462A1
• Time in Patent Office: Days
• US Class Current: 424/9.1
• CPC Class Codes: A61K 41/10 Inactivation or decontamination of a medicinal preparation prior to administration to an animal or a person
• CPC Class Codes: A61K 49/1857 the organic macromolecular compound being obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. PLGA
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: C07K 1/22 Affinity chromatography or related techniques based upon selective absorption processes
• CPC Class Codes: C07K 1/32 as complexes
• CPC Class Codes: G01N 2800/2821 Alzheimer
• CPC Class Codes: G01N 2800/2828 Prion diseases
• CPC Class Codes: G01N 33/6896 Neurological disorders, e.g. Alzheimer's disease

Abstract

A method for separation of an aggregated misfolded protein from an environment including a non-aggregating normal form of the protein includes contacting both the misfolded and normal protein with a conjugated polyelectrolyte (CPE) and separating the CPE/protein complex from the other constituents of the sample.

Claims

1. A method for separation of an aggregated misfolded protein from an environment comprising a non-aggregating normal form of the protein, comprising contacting both said misfolded and normal protein with a conjugated polyelectrolyte (CPE) and separating the CPE/protein complex from the other constituents of the sample.

2. The method according to claim 1, wherein the polyelectrolyte comprises copolymers or homopolymers of thiophene, pyrrole, aniline, furan, phenylene, vinylene, fluorene, ethylenedioxythiophene or their substituted forms.

3. The method according claim 1, wherein said conjugated polyelectrolyte has one or more ionic side chain and/or end terminal functionalities.

4. The method according to claim 3, wherein the ionic functionalities comprise one or more zwitterionic, anionic and cationic side chain functionalities.

5. The method according to claim 4, wherein said ionic side chain and/or end terminal functionalities are selected from the group consisting of amino acids, amino acid derivatives, neurotransmitters, monosaccharides, nucleic acids, DNA, RNA, peptides, amino acids, histidine, histidine₁₀, proteins, peptide scaffolds, biotin, avidin, streptavidin, chelators, active groups, antibodies, enzymes, ligands, receptor ligands, steroids, biomolecules or other molecules, nanoparticles, microparticles, gold nanoparticles, gold microparticles, magnetic beads, protein coated beads, peptide coated beads, supramagnetic beads or particles, gadolinium nanoparticle, gadolinium ions, lanthanide doped nanoparticles, lanthanide-doped gadolinium oxide nanoparticles, lanthanide particles or combinations and chemically modified derivatives thereof.

6. The method according to claim 1, wherein the method is performed in vitro.

7. The method according to any of claim 1, wherein the method is performed in vivo.

8. The method according to claim 1, wherein the CPE is bound to a solid support.

9. The method according to claim 1, further comprising detection of the CPE/protein complex.

10. The method according to claim 1, wherein binding between CPE and misfolded protein and detection of the CPE/protein complex is performed simultaneously.

11. The method according to claim 9, wherein the CPE/protein complex and the detection means are on separate sides of a barrier, such as a tube wall, a membrane or skin.

12. A diagnostic preparation comprising an optionally functionalized CPE and optionally a pharmaceutically acceptable carrier.

13. The preparation according to claim 12, wherein said conjugated polyelectrolyte has one or more ionic side chain and/or end terminal functionalities and wherein said ionic side chain and/or end terminal functionalities are selected from the group consisting of amino acids, amino acid derivatives, neurotransmitters, monosaccharides, nucleic acids, DNA, RNA, peptides, amino acids, histidine, histidine₁₀, proteins, peptide scaffolds, biotin, avidin, streptavidin, chelators, active groups, antibodies, enzymes, ligands, receptor ligands, steroids, biomolecules or other molecules, nanoparticles, microparticles, gold nanoparticles, gold microparticles, magnetic beads, protein coated beads, peptide coated beads, supramagnetic beads or particles, gadolinium nanoparticle, gadolinium ions, lanthanide doped nanoparticles, lanthanide-doped gadolinium oxide nanoparticles, lanthanide particles or combinations and chemically modified derivatives thereof.