WO1992006378A1 - Agents de diagnostic fluorescents auto-rassemblants - Google Patents

Agents de diagnostic fluorescents auto-rassemblants Download PDF

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Publication number
WO1992006378A1
WO1992006378A1 PCT/US1991/007380 US9107380W WO9206378A1 WO 1992006378 A1 WO1992006378 A1 WO 1992006378A1 US 9107380 W US9107380 W US 9107380W WO 9206378 A1 WO9206378 A1 WO 9206378A1
Authority
WO
WIPO (PCT)
Prior art keywords
components
aldehyde
hydrazine
target
cells
Prior art date
Application number
PCT/US1991/007380
Other languages
English (en)
Inventor
Darryl C. Rideout
Original Assignee
The Scripps Research Institute
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 The Scripps Research Institute filed Critical The Scripps Research Institute
Priority to JP3517584A priority Critical patent/JPH06504365A/ja
Publication of WO1992006378A1 publication Critical patent/WO1992006378A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/001—Preparation for luminescence or biological staining
    • A61K49/0013—Luminescence
    • A61K49/0017—Fluorescence in vivo
    • A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
    • A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/001—Preparation for luminescence or biological staining
    • A61K49/0013—Luminescence
    • A61K49/0017—Fluorescence in vivo
    • A61K49/005—Fluorescence in vivo characterised by the carrier molecule carrying the fluorescent agent
    • A61K49/0058—Antibodies
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/531—Production of immunochemical test materials
    • G01N33/532—Production of labelled immunochemicals
    • G01N33/533—Production of labelled immunochemicals with fluorescent label
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
    • G01N33/582—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances with fluorescent label

Definitions

  • U.S. Patent 4,812,449 issued to the applicant herein and incorporated herein by reference discloses the general approach of providing active materials in the form of component precursors so as to permit self assembly in a target microenviron ent.
  • a target refers to an organism, tissue, cell, or other biologically responsive material which it is desired to modify.
  • the target will occur in a general environment which may be an j_n vitro or an n vivo environment, and supplies its own “microenvironment”.
  • the patent discloses a large number of reaction types which may be employed to form a conjugate jLn situ, including hydrazone formation.
  • the invention herein represents a particularly advantageous specific embodiment of this general approach—namely, use of a self-assembling conjugate to generate fluorescence for detection of target conditions either jj vivo or ij vitro.
  • a self-assembling conjugate to generate fluorescence for detection of target conditions either jj vivo or ij vitro.
  • it is possible to enhance the selectivity for target by conjugating one or both of the components of the self-assembling conjugate to a target-specific ligand.
  • Figure 2 shows the ability of the conjugate M preformed or formed jln situ to label MCF-7 cells .in vitro.
  • Figure 4 shows the effect of compounds K, M, and L on fluorescence emitted by MIA PaCa cells in . vitro.
  • Figure 5 shows an isobologram for inhibition of MIA PaCa cells by various combinations of components K and L.
  • the invention method relies in part on the ability of the components of the conjugates to migrate preferentially to the target organism, cell or tissue.
  • suitable targets include those moieties whose detection is of medical interest, such as tumor cells, infectious organisms, diseased tissue, and the like.
  • the homing specificity of the components can be enhanced by coupling the component to a targeting ligand using general coupling methods known in the art, including direct coupling, but preferentially utilizing linker molecules which permit more controlled coupling reactions.
  • Commercially available linkers such as those from Pierce Chemical Company, Rockford, IL, may be used, for example.
  • Figure 2A and B show the phase contrast photograph and fluorescent micrograph of MCF-7 cells treated with a saline control. No fluorescence is seen.
  • C, E and G show the phase contrast photographs and D, F and H show fluorescence micrographs of MCF-7 cells which have been treated with reagents L, K or M, respectively, for 24 hours.
  • panels D and F neither 11.2 ⁇ g/ml L or 16.8 ⁇ g/ml of K provided any fluorescence labeling for these cells.
  • only 5 2.6 ⁇ g/ml of M provided a high contrast micrograph.
  • panels A 1 and B 1 are the . corresponding results for MCF-7 cells incubated simultaneously for 24 hours with 5.6 ⁇ g/ml L and 8.5 ⁇ g/ml K.
  • Panel B shows that a fluorescent signal is
  • panels C and D' show that if L is administered before , even in higher amount, no fluorescence is obtained. Administration of 11.2 ⁇ g/ml L for 24 hours followed by washing and treatment with 16.8 ⁇ g/ml K for 24 hours did not result

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Hematology (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Urology & Nephrology (AREA)
  • Cell Biology (AREA)
  • Physics & Mathematics (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Epidemiology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

On alimente séparément un milieu en composés de conjugués fluorescents qui se lient en présence d'une cellule ou d'un tissu d'organisme cible, de sorte que l'on obtient un conjugué fluorescent pouvant servir à détecter ladite cible.
PCT/US1991/007380 1990-10-04 1991-10-03 Agents de diagnostic fluorescents auto-rassemblants WO1992006378A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP3517584A JPH06504365A (ja) 1990-10-04 1991-10-03 自己組み立て蛍光診断薬

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US59247790A 1990-10-04 1990-10-04
US592,477 1990-10-04

Publications (1)

Publication Number Publication Date
WO1992006378A1 true WO1992006378A1 (fr) 1992-04-16

Family

ID=24370806

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1991/007380 WO1992006378A1 (fr) 1990-10-04 1991-10-03 Agents de diagnostic fluorescents auto-rassemblants

Country Status (3)

Country Link
EP (1) EP0554331A1 (fr)
JP (1) JPH06504365A (fr)
WO (1) WO1992006378A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0534380A1 (fr) * 1991-09-24 1993-03-31 Kyoto Daiichi Kagaku Co., Ltd. Agent et procédé pour augmenter la chemiluminescence
US20100216132A1 (en) * 2008-09-05 2010-08-26 Schwartz David A Methods and compositions for direct detection of dna damage

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4671958A (en) * 1982-03-09 1987-06-09 Cytogen Corporation Antibody conjugates for the delivery of compounds to target sites
US4812449A (en) * 1986-07-03 1989-03-14 Scripps Clinic And Research Foundation In situ active compound assembly
US4868103A (en) * 1986-02-19 1989-09-19 Enzo Biochem, Inc. Analyte detection by means of energy transfer
US4937183A (en) * 1988-02-03 1990-06-26 Cytogen Corporation Method for the preparation of antibody-fragment conjugates
US5047227A (en) * 1988-02-08 1991-09-10 Cytogen Corporation Novel and improved antibodies for site specific attachment of compounds

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4671958A (en) * 1982-03-09 1987-06-09 Cytogen Corporation Antibody conjugates for the delivery of compounds to target sites
US4868103A (en) * 1986-02-19 1989-09-19 Enzo Biochem, Inc. Analyte detection by means of energy transfer
US4812449A (en) * 1986-07-03 1989-03-14 Scripps Clinic And Research Foundation In situ active compound assembly
US4937183A (en) * 1988-02-03 1990-06-26 Cytogen Corporation Method for the preparation of antibody-fragment conjugates
US5047227A (en) * 1988-02-08 1991-09-10 Cytogen Corporation Novel and improved antibodies for site specific attachment of compounds

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Analyst (London), Volume 115, No. 11, issued 1990, UZU et al., "Fluorogenic reagents: 4-amino sulfonyl-7-hydrazion-2,1.3-benzoxadiazol. 4-(N.N-dimethy)-aminosulfonyl)-7-hydrazino-2.1.3.-benzoxadiazole and 4-hydrazion-7-hydrazino-2.1.3-benzoxadiazole and 4-hydrazino-7-nitro-2.1.3-benzoxadiazole hydrazing for aldehydes and ketones", pages 1477-82. see CHEM. Abstract No.114:55043u. *
Chemical & Pharmaceudical Bulletin, Volume 17, No. 11, issued 1969, MIZUTAN et al., "Fluorescence Assay of aOxo Acids with 4-Hydrazino-2-stibazole", pages 2340-2348, see entire document. *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0534380A1 (fr) * 1991-09-24 1993-03-31 Kyoto Daiichi Kagaku Co., Ltd. Agent et procédé pour augmenter la chemiluminescence
US20100216132A1 (en) * 2008-09-05 2010-08-26 Schwartz David A Methods and compositions for direct detection of dna damage
EP2604702A1 (fr) * 2008-09-05 2013-06-19 The University of Chicago Procédés et compositions pour la détection directe de lésions de l'ADN
US8580516B2 (en) * 2008-09-05 2013-11-12 University Of Chicago Methods and compositions for direct detection of DNA damage

Also Published As

Publication number Publication date
JPH06504365A (ja) 1994-05-19
EP0554331A1 (fr) 1993-08-11

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