ES2529256T3 - Sondas fluorescentes para la detección de ADN mediante hibridación con una sensibilidad mejorada y baja señal de fondo - Google Patents

Sondas fluorescentes para la detección de ADN mediante hibridación con una sensibilidad mejorada y baja señal de fondo Download PDF

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ES2529256T3
ES2529256T3 ES04817540.0T ES04817540T ES2529256T3 ES 2529256 T3 ES2529256 T3 ES 2529256T3 ES 04817540 T ES04817540 T ES 04817540T ES 2529256 T3 ES2529256 T3 ES 2529256T3
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nucleic acid
fluorescence
oligonucleotide
oligonucleotide probe
linker
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Sergey Lokhov
Eugene Lukhtanov
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Nanogen Inc
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Epoch Biosciences Inc
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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6813—Hybridisation assays
    • C12Q1/6816—Hybridisation assays characterised by the detection means
    • C12Q1/6818—Hybridisation assays characterised by the detection means involving interaction of two or more labels, e.g. resonant energy transfer
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
    • C07H21/04—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6813—Hybridisation assays
    • C12Q1/6816—Hybridisation assays characterised by the detection means
    • C12Q1/682—Signal amplification
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6844—Nucleic acid amplification reactions
    • C12Q1/686—Polymerase chain reaction [PCR]
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/156—Polymorphic or mutational markers
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/14—Heterocyclic carbon compound [i.e., O, S, N, Se, Te, as only ring hetero atom]
    • Y10T436/142222—Hetero-O [e.g., ascorbic acid, etc.]
    • Y10T436/143333—Saccharide [e.g., DNA, etc.]

Abstract

Una sonda de oligonucleótidos que comprende una porción de oligonucleótido que tiene un extremo 3' y un extremo 5', una unidad estructural de ligador del surco menor anexada a al menos una de dichas unidades de nucleótidos a través de un grupo enlazante el cual liga covalentemente la unidad estructural ligadora del surco menor al oligonucleótido y un fluoróforo y detenedor, teniendo dicha sonda la fórmula;**Fórmula** en donde MB es un ligador del surco menor; Q es un detenedor; FI es un fluoróforo; [A-B]n representa un oligómero de ácido nucleico que tienen n unidades, en donde n es un entero de 5 a 50; cada A representa independientemente un componente de esqueleto de ácido nucleico seleccionado del grupo que consiste de un esqueleto de fosfato de azúcar, un esqueleto modificado de fosfato de azúcar, una cadena principal de ácido nucleico bloqueado, un esqueleto peptídico o una variante del mismo usado en la preparación de ácido nucleico; y cada B representa independientemente una base de ácido nucleico, una base modificada o un análogo de base; K es un enlace o un grupo enlazante; y W es un grupo enlazante trivalente que provee suficiente espacio entre MB, FI y [A-B]n de tal forma que (i) MB se une a un surco menor dúplex formado cuando dicha sonda de oligonucleótidos se hibrida a su secuencia complementaria; (ii) en una forma no hibridada, la fluorescencia de FI en dicha sonda de oligonucleótidos es menos de 10% de la fluorescencia no detenida; y (iii) cuando dicha sonda de oligonucleótidos se hibrida a dicha secuencia objetivo, la fluorescencia de FI es al menos 50% de su fluorescencia no detenida.

Description

imagen1
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E04817540
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Tabla 1
Literatura de la Estructura
λmax nm; εM-1 cm -1; Solvente Estructura modificada del enlazador Q-K
464
imagen17
440 imagen18
imagen19
540; 40,000 MeOH imagen20
imagen21
549 37,000 EtOH imagen22
590 48,978 CHCl3
imagen23
601 40,738 CHCl3 imagen24
623 48,000 CHCl3
imagen25
656 100,000 CHCl3 imagen26
656 53,043
598
582
18
E04817540
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(continuación)
Literatura de la Estructura
λmax nm; εM-1 cm -1; Solvente Estructura modificada del enlazador Q-K
652
554 50,000
673.5
imagen27
809 imagen28
592 46,000
601 51,000
623 48,000
632 Predicho
Los anteriores detenedores cubren el rango de aproximadamente 400 a 800 nm, y muchos demuestran detención mejorada cuando se unen a un conjugado MB-Fl-ODN-Q. Mientras que las versiones modificadas ilustran NH
5 (CH2CH2OH) como un grupo enlazante preferido para ser usado para acoplar el detenedor a oligonucleótidos o soporte sólido, ejemplos de otros enlazadores adecuados son conocidos en la técnica o se proveen aquí o pueden ser preparados a partir de detenedores derivados tales como los de la Tabla 1.
Detenedores preferidos para cada uno de los aspectos de la invención presente son seleccionados de aquellos en la tabla anterior, así como detenedores bis azo (Patente de los Estados Unidos No. 6,790,945) y los colorantes de
10 Biosearch Technologies, Inc. (provistos cono detenedores Black Hole™: BH-1, BH-2 y BH-3), Dabcilo, TAMRA y rodamina de carboxitetrametilo.
Fluoróforos
19
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E04817540
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Tabla 2: Secuencia de sondas objetivo, cebadoras y fluorogénicas
Porción de las secuencias objetivo de ARNT-01 ((SEQ ID NO:15); Sonda (SEQ ID NOS:16-19) y cebador se muestran en Negrita Subrayada. FAM esfluoresceína, YY es Yakima Yellow, Q es Detenedor Eclipse y MB es DPI3
imagen44
Sondas Eclipse
Sondas nuevas
MB-Q-GTATGTCTCTGACTCC-FAM
MB-FAM-GTATGTCTCTGACTCC-Q
MB-Q-GTATGTCTCTGACTCC-YY
MB-YY-GTATGTCTCTGACTCC-Q
35
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Claims (1)

  1. imagen1
    imagen2
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    imagen6
ES04817540.0T 2003-10-28 2004-10-27 Sondas fluorescentes para la detección de ADN mediante hibridación con una sensibilidad mejorada y baja señal de fondo Active ES2529256T3 (es)

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US51552303P 2003-10-28 2003-10-28
US515523P 2003-10-28
PCT/US2004/037981 WO2005043127A2 (en) 2003-10-28 2004-10-27 Fluorescent probes for dna detection by hybridization with improved sensitivity and low background

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EP (1) EP1687609B1 (es)
JP (1) JP4942484B2 (es)
AU (1) AU2004286352A1 (es)
CA (1) CA2542768A1 (es)
DK (1) DK1687609T3 (es)
ES (1) ES2529256T3 (es)
PL (1) PL1687609T3 (es)
PT (1) PT1687609E (es)
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WO (1) WO2005043127A2 (es)

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EP1687609A2 (en) 2006-08-09
US7381818B2 (en) 2008-06-03
US7759126B2 (en) 2010-07-20
CA2542768A1 (en) 2005-05-12
US20080293586A1 (en) 2008-11-27
JP4942484B2 (ja) 2012-05-30
EP1687609A4 (en) 2012-06-20
JP2007509634A (ja) 2007-04-19
WO2005043127A3 (en) 2006-11-09
WO2005043127A2 (en) 2005-05-12
PT1687609E (pt) 2015-03-02
EP1687609B1 (en) 2014-12-10
AU2004286352A1 (en) 2005-05-12
DK1687609T3 (en) 2015-01-12
US20050214797A1 (en) 2005-09-29
SI1687609T1 (sl) 2015-03-31
PL1687609T3 (pl) 2015-05-29

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