WO1994004185A3 - Method of inhibiting reduction of disulfide bonds - Google Patents

Method of inhibiting reduction of disulfide bonds Download PDF

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Publication number
WO1994004185A3
WO1994004185A3 PCT/US1993/007805 US9307805W WO9404185A3 WO 1994004185 A3 WO1994004185 A3 WO 1994004185A3 US 9307805 W US9307805 W US 9307805W WO 9404185 A3 WO9404185 A3 WO 9404185A3
Authority
WO
WIPO (PCT)
Prior art keywords
disulfide bonds
inhibiting
membrane
useful
macromolecules
Prior art date
Application number
PCT/US1993/007805
Other languages
French (fr)
Other versions
WO1994004185A2 (en
Inventor
Hughes J-P Ryser
Original Assignee
Univ Boston
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Univ Boston filed Critical Univ Boston
Priority to EP93920204A priority Critical patent/EP0656787A1/en
Publication of WO1994004185A2 publication Critical patent/WO1994004185A2/en
Publication of WO1994004185A3 publication Critical patent/WO1994004185A3/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/06—Tripeptides
    • A61K38/063—Glutathione
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/095—Sulfur, selenium, or tellurium compounds, e.g. thiols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/28—Compounds containing heavy metals
    • A61K31/305—Mercury compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/005—Enzyme inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Endocrinology (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)

Abstract

This invention pertains to a method of altering (inhibiting or enhancing), directly or indirectly, reduction of disulfide bonds of membrane-bound macromolecules, particularly proteins, and, as a result, inhibiting (totally or partially) or enhancing the cellular penetration and the respective effects of these macromolecules. In particular, the present invention relates to a method of inhibiting, directly or indirectly, the reductive function of cell membranes, particularly the cell surface (plasma) membrane, which is capable of cleaving disulfide bonds in membrane-bound proteins which must be cleaved for the proteins to enter cells and produce their respective effects on cells they have entered. Cleavage of disulfide bonds in this manner is a metabolic step required for the ultimate function of the protein or macromolecule. As described herein, applicant has demonstrated that the reductive function of cell surface membranes is catalyzed by protein disulfide isomerase (PDI). The method of the present invention is useful to prevent adverse effects of toxins, such as diphtheria toxin, on cells. It is also useful in preventing infection (e.g., viral or bacterial) or the spread of an established infection. The method may also be useful in enhancing uptake of macromolecules whose presence within a cell is desired.
PCT/US1993/007805 1992-08-19 1993-08-18 Method of inhibiting reduction of disulfide bonds WO1994004185A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP93920204A EP0656787A1 (en) 1992-08-19 1993-08-18 Method of inhibiting reduction of disulfide bonds

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US93236992A 1992-08-19 1992-08-19
US07/932,369 1992-08-19
US5219493A 1993-04-22 1993-04-22
US08/052,194 1993-04-22

Publications (2)

Publication Number Publication Date
WO1994004185A2 WO1994004185A2 (en) 1994-03-03
WO1994004185A3 true WO1994004185A3 (en) 2004-04-29

Family

ID=26730314

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1993/007805 WO1994004185A2 (en) 1992-08-19 1993-08-18 Method of inhibiting reduction of disulfide bonds

Country Status (2)

Country Link
EP (1) EP0656787A1 (en)
WO (1) WO1994004185A2 (en)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PT100914A (en) * 1991-09-30 1993-10-29 Jess G Thoene USE OF COMPOUNDS ABLE TO SUFFER A MIXED DISSOLFURET EXCHANGE, WITH A DISSULFURET LIGACATION, IN THE TREATMENT OF HIV INFECTION
US5554655A (en) * 1991-09-30 1996-09-10 Jess G. Thoene Method of treating HIV infection
AU7931094A (en) * 1993-10-15 1995-05-04 Jess G. Thoene Prevention of hiv infection
US5725870A (en) * 1993-10-15 1998-03-10 Thoene; Jess G. Methods, composites and articles for contraception
US5532154A (en) * 1994-03-21 1996-07-02 Research Development Foundation Mutated alpha virus
US6977142B2 (en) * 2003-09-23 2005-12-20 Agy Therapeutics, Inc. High-throughput turbidometric assay for screening inhibitors of protein disulfide isomerase activity
PL227562B1 (en) 2011-09-23 2017-12-29 Wrocławskie Centrum Badań Eit + Spółka Z Ograniczoną Application of the bacitracin antibiotic for the hydrolytic degradation of RNA

Non-Patent Citations (10)

* Cited by examiner, † Cited by third party
Title
CHIACCHIA, K.B.: "REOXIDATION OF THE CLASS I DISULFIDES OF THE RAT ADIPOCYTE INSULIN RECEPTOR IS DEPENDENT UPON THE PRESCENCE OF INSULIN: THE CLASS I DISULFIDE OF THE INSULIN RECEPTOR IS EXTRACELLULAR", BIOCHEMISTRY, vol. 27, no. 13, 28 June 1988 (1988-06-28), pages 4894 - 4902 *
FEENER, E.P. ET AL: "CLEAVAGE OF DISULFIDE BONDS IN ENDOCYTOSED MACROMOLECULES", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 265, no. 31, 5 November 1990 (1990-11-05), pages 18780 - 18785 *
FEENER, EDWARD P.: "THE ROLE OF THE PLASMA MEMBRANE AND A NON-LYSOSOMAL COMPARTMENT IN THE DISULFIDE CLEAVAGE OF ENDOCYTOSED MACROMOLECULES", DISSERTATION ABSTRACTS INTERNATIONAL B, vol. 51, no. 1, July 1990 (1990-07-01), pages 182B *
GIDWITZ, S. ET AL: "DIFFERENCES IN VIRION STABILITY AMONG SINDBIS VIRUS PATHOGENESIS MUTANTS", VIRUS RESEARCH, vol. 10, no. 2,3, 1988, pages 225 - 240 *
LASKY, L.A. ET AL: "DELINEATION OF A REGION OF THE HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 GP120 GLYCOPROTEIN CRITICAL FOR INTERACTION WITH THE CD4 RECEPTOR", CELL, vol. 50, 1987, pages 975 - 985 *
MANDEL, R. ET AL: "INHIBITION OF A REDUCTIVE FUNCTION OF THE PLASMA MEMBRANE BY BACITRACIN AND ANTIBODIES AGAINST PROTEIN DISULFIDE-ISOMERASE", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES, vol. 90, no. 9, 1 May 1993 (1993-05-01), pages 4112 - 4116 *
MEYER, W.J. ET AL: "CONFORMATIONAL ALTERATION OF SINDBIS VIRION GLYCOPROTEINS INDUCED BY HEAT, REDUCING AGENTS OR LOW PH", JOURNAL OF VIROLOGY, vol. 66, no. 6, June 1992 (1992-06-01), pages 3504 - 3513 *
RYSER, H. J.-P. ET AL: "CELL SURFACE SULFHYDRYLS ARE REQUIRED FOR THE TOXICITY OF DIPHTHERIA TOXIN BUT NOT OF RICIN IN CHINESE HAMSTER OVARY CELLS", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 266, no. 28, 5 October 1991 (1991-10-05), pages 18439 - 18442 *
SHEN, W-C. ET AL: "DISULFIDE AND OTHER SPACERS FOR THE INTRACELLULAR RELEASE OF DRUGS FROM POLYMERIC CARRIERS", POLYMER PREPRINTS, vol. 27, no. 1, April 1986 (1986-04-01), pages 9 - 10 *
YOSHIMORI, T. ET AL: "PROTEIN DISULFIDE-ISOMERASE IN RAT EXOCRINE PANCREATIC CELLS IS EXPORTED FROM THE ENDOPLASMIC RETICULUM DESPITE POSSESSING THE RETENTION SIGNAL", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 265, no. 26, 15 September 1990 (1990-09-15), pages 15984 - 90 *

Also Published As

Publication number Publication date
WO1994004185A2 (en) 1994-03-03
EP0656787A1 (en) 1995-06-14
EP0656787A4 (en) 1994-04-15

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