公开(公告)号：US09150922B2

公开(公告)日：2015-10-06

申请号：US14109475

申请日：2013-12-17

Applicant: LIFE TECHNOLOGIES CORPORATION

Inventor： Rosaria Haugland ,  Ching-Ying Cheung ,  Stephen Yue

IPC: C07D401/04 ,  C07D209/14 ,  C12Q1/68 ,  C07D209/12 ,  C07D209/24 ,  C09B23/12

CPC classification number: C12Q1/6876 ,  C07D209/12 ,  C07D209/14 ,  C07D209/24 ,  C07D401/04 ,  C09B23/12

Abstract: The present invention provides methods and non-fluorescent carbocyanine quencher compounds having the general formula: Wherein the A moiety is a substituted pyridinium, unsubstituted pyridinium, substituted quinolinium, unsubstituted quinolinium, substituted benzazolium, unsubstituted benzazolium, substituted indolinium, or substituted indolinium. The invention further provides luminescent donor molecule-quencher pairs and luminescent donor molecule-quencher-luminescent acceptor molecule conjugates wherein the quencher is a cyanine compound of the present invention. The energy transfer pairs are used to detect an analyte of interest in a sample.

Abstract translation: 本发明提供了具有以下通式的方法和非荧光碳花青猝灭剂：其中A部分是取代的吡啶鎓，未取代的吡啶鎓，取代的喹啉鎓，未取代的喹啉鎓，取代的苯并唑鎓，未取代的苯并咪唑鎓，取代的吲哚鎓或取代的吲哚啉鎓。 本发明还提供了发光供体分子猝灭剂对和发光供体分子 - 猝灭剂 - 发光受体分子缀合物，其中猝灭剂是本发明的花青化合物。 能量转移对用于检测样品中感兴趣的分析物。

公开(公告)号：US09018396B2

公开(公告)日：2015-04-28

申请号：US14030835

申请日：2013-09-18

Applicant: Life Technologies Corporation

Inventor： Wai-Yee Leung ,  Ching-Ying Cheung ,  Stephen Yue

IPC: C07D209/56 ,  C07D209/02 ,  C07D417/00 ,  C07D498/04 ,  A61K41/00 ,  C07C66/02 ,  C07D209/08 ,  C07D209/12 ,  C07D209/14 ,  C07D209/16 ,  C07D209/18 ,  C07D209/24 ,  C07D209/54 ,  C07D209/60 ,  C07D209/96 ,  C07D401/04 ,  C07D403/06 ,  C07D403/12 ,  C07D403/14 ,  C07D417/06 ,  C07D417/14 ,  C07D471/04 ,  C07K1/13 ,  C09B23/02 ,  C40B70/00 ,  G01N1/30 ,  G01N33/533 ,  G01N33/58 ,  G01N31/22

CPC classification number: G01N1/30 ,  A61K41/0057 ,  C07C66/02 ,  C07D209/08 ,  C07D209/12 ,  C07D209/14 ,  C07D209/16 ,  C07D209/18 ,  C07D209/24 ,  C07D209/54 ,  C07D209/60 ,  C07D209/96 ,  C07D401/04 ,  C07D403/06 ,  C07D403/12 ,  C07D403/14 ,  C07D417/06 ,  C07D417/14 ,  C07D471/04 ,  C07D498/04 ,  C07K1/13 ,  C09B23/02 ,  C09B23/06 ,  C09B23/083 ,  C09B23/107 ,  C12Q1/6825 ,  C40B70/00 ,  G01N31/22 ,  G01N33/533 ,  G01N33/535 ,  G01N33/58 ,  G01N33/581 ,  G01N33/582 ,  G01N2001/302 ,  Y10T436/143333

Abstract: Chemically reactive carbocyanine dyes incorporating an indolium ring moiety that is substituted at the 3-position by a reactive group or by a conjugated substance, and their uses, are described. Conjugation through this position results in spectral properties that are uniformly superior to those of conjugates of spectrally similar dyes wherein attachment is at a different position. The invention includes derivative compounds having one or more benzo nitrogens.

公开(公告)号：US08865904B2

公开(公告)日：2014-10-21

申请号：US13861123

申请日：2013-04-11

Applicant: Life Technologies Corporation

Inventor： Jolene Bradford ,  Ching-Ying Cheung ,  Shih-Jung Huang ,  Patrick Pinson ,  Stephen Yue

IPC: C07D215/00 ,  C07D417/04 ,  C07D215/10 ,  C07D277/72 ,  C07D277/74 ,  G01N21/64 ,  C07D417/14 ,  C07D417/06 ,  C07D215/227

CPC classification number: G01N33/582 ,  C07D215/10 ,  C07D215/227 ,  C07D277/72 ,  C07D277/74 ,  C07D417/04 ,  C07D417/06 ,  C07D417/14 ,  C12Q1/6876 ,  G01N21/6428 ,  G01N21/6486 ,  G01N2021/6439 ,  G01N2201/06113 ,  Y10T436/143333

Abstract: Chemical compounds having a high selectivity for double stranded DNA over RNA and single stranded DNA are disclosed. The chemical compounds are stains that become fluorescent upon illumination and interaction with double stranded DNA, but exhibit reduced or no fluorescence in the absence of double stranded DNA. The compounds can be used in a variety of biological applications to qualitatively or quantitatively assay DNA, even in the presence of RNA.

Abstract translation: 公开了对RNA和单链DNA具有对双链DNA的高选择性的化合物。 化学化合物是在照射时变成荧光并与双链DNA相互作用的污渍，但在不存在双链DNA的情况下表现出减少的或没有荧光。 该化合物可用于各种生物学应用中，以定性或定量测定DNA，即使在RNA的存在下。

公开(公告)号：US20130178395A1

公开(公告)日：2013-07-11

申请号：US13784413

申请日：2013-03-04

Applicant: Life Technologies Corporation

Inventor： Richard Haugland ,  Stephen Yue

IPC: C12Q1/68 ,  G01N33/68

CPC classification number: C09B23/02 ,  C12Q1/6816 ,  C12Q1/6876 ,  G01N1/30 ,  G01N27/44726 ,  G01N33/52 ,  G01N33/5308 ,  G01N33/531 ,  G01N33/582 ,  G01N33/68 ,  G01N2001/302 ,  Y10S436/80 ,  Y10T436/143333 ,  C12Q2563/173 ,  C12Q2563/107

Abstract: Unsymmetrical cyanine dyes that incorporate an aza-benzazolium ring moiety are described, including cyanine dyes substituted by a cationic side chain, monomeric and dimeric cyanine dyes, chemically reactive cyanine dyes, and conjugates of cyanine dyes. The subject dyes are virtually non-fluorescent when diluted in aqueous solution, but exhibit bright fluorescence when associated with nucleic acid polymers such as DNA or RNA, or when associated with detergent-complexed proteins. A variety of applications are described for detection and quantitation of nucleic acids and detergent-complexed proteins in a variety of samples, including solutions, electrophoretic gels, cells, and microorganisms.

公开(公告)号：US10005908B2

公开(公告)日：2018-06-26

申请号：US15194911

申请日：2016-06-28

Applicant: LIFE TECHNOLOGIES CORPORATION

Inventor： Jason Dallwig ,  David Hagen ,  Ching-Ying Cheung ,  Gerald Thomas ,  Stephen Yue

IPC: C07D277/64 ,  C07D417/06 ,  C09B23/16 ,  C09B23/01 ,  C09B23/06 ,  G01N33/53 ,  C09B23/04 ,  C09B23/10 ,  C12Q1/68

CPC classification number: C09B23/164 ,  C07D277/64 ,  C07D417/06 ,  C09B23/0008 ,  C09B23/04 ,  C09B23/06 ,  C09B23/107 ,  C12Q1/6806 ,  C12Q1/6876 ,  C12Q2600/16 ,  G01N33/5308 ,  Y10T436/143333

Abstract: Cyanine dye compounds having a substituted methine moiety that are nucleic acid stains, particularly for fluorescent staining of RNA, including compounds having the formula where R1 is a C1-C6 alkyl, sulfoalkyl, carboxyalkyl or C1-C6 alkoxy; each R2 is independently selected from the group consisting of H, C1-C6 alkyl, C1-C6 alkoxy, fused benzo, trifluoromethyl, amino, sulfo, carboxy and halogen, that is optionally further substituted; at least one of R3, R4, and R5 is an alkyl, aryl, heteroaryl, cyclic, or heterocyclic moiety that is optionally substituted by alkyl, amino, aminoalkyl, carboxy, nitro, or halogen; and the remaining R3, R4 or R5 are hydrogen; X is S, O, or Se; and D is a substituted or unsubstituted pyridinium, quinolinium or benzazolium moiety.

公开(公告)号：US09382425B2

公开(公告)日：2016-07-05

申请号：US14508573

申请日：2014-10-07

Applicant: LIFE TECHNOLOGIES CORPORATION

Inventor： Richard Haugland ,  Stephen Yue

IPC: C07D215/00 ,  C07D417/06 ,  C09B23/02 ,  C12Q1/68 ,  G01N1/30 ,  G01N27/447 ,  G01N33/52 ,  G01N33/53 ,  G01N33/531 ,  G01N33/58 ,  G01N33/68

CPC classification number: C09B23/02 ,  C12Q1/6816 ,  C12Q1/6876 ,  G01N1/30 ,  G01N27/44726 ,  G01N33/52 ,  G01N33/5308 ,  G01N33/531 ,  G01N33/582 ,  G01N33/68 ,  G01N2001/302 ,  Y10S436/80 ,  Y10T436/143333 ,  C12Q2563/173 ,  C12Q2563/107

Abstract: Unsymmetrical cyanine dyes that incorporate an aza-benzazolium ring moiety are described, including cyanine dyes substituted by a cationic side chain, monomeric and dimeric cyanine dyes, chemically reactive cyanine dyes, and conjugates of cyanine dyes. The subject dyes are virtually non-fluorescent when diluted in aqueous solution, but exhibit bright fluorescence when associated with nucleic acid polymers such as DNA or RNA, or when associated with detergent-complexed proteins. A variety of applications are described for detection and quantitation of nucleic acids and detergent-complexed proteins in a variety of samples, including solutions, electrophoretic gels, cells, and microorganisms.

公开(公告)号：US09366676B2

公开(公告)日：2016-06-14

申请号：US14797415

申请日：2015-07-13

Applicant: LIFE TECHNOLOGIES CORPORATION

Inventor： Jolene Bradford ,  Ching-Ying Cheung ,  Shih-Jung Huang ,  Patrick Pinson ,  Stephen Yue

IPC: C07D215/00 ,  G01N33/58 ,  G01N21/64 ,  C07D215/10 ,  C07D215/227 ,  C07D277/72 ,  C07D277/74 ,  C07D417/04 ,  C07D417/06 ,  C07D417/14 ,  C12Q1/68

CPC classification number: G01N33/582 ,  C07D215/10 ,  C07D215/227 ,  C07D277/72 ,  C07D277/74 ,  C07D417/04 ,  C07D417/06 ,  C07D417/14 ,  C12Q1/6876 ,  G01N21/6428 ,  G01N21/6486 ,  G01N2021/6439 ,  G01N2201/06113 ,  Y10T436/143333

Abstract: Chemical compounds having a high selectivity for double stranded DNA over RNA and single stranded DNA are disclosed. The chemical compounds are stains that become fluorescent upon illumination and interaction with double stranded DNA, but exhibit reduced or no fluorescence in the absence of double stranded DNA. The compounds can be used in a variety of biological applications to qualitatively or quantitatively assay DNA, even in the presence of RNA.

公开(公告)号：US09115397B2

公开(公告)日：2015-08-25

申请号：US14488751

申请日：2014-09-17

Applicant: LIFE TECHNOLOGIES CORPORATION

Inventor： Jolene Bradford ,  Ching-Ying Cheung ,  Shih-Jung Huang ,  Patrick Pinson ,  Stephen Yue

IPC: C07D215/00 ,  C12Q1/68 ,  C07D215/10 ,  C07D215/227 ,  C07D277/72 ,  C07D277/74 ,  C07D417/04 ,  C07D417/06 ,  C07D417/14 ,  G01N21/64

CPC classification number: G01N33/582 ,  C07D215/10 ,  C07D215/227 ,  C07D277/72 ,  C07D277/74 ,  C07D417/04 ,  C07D417/06 ,  C07D417/14 ,  C12Q1/6876 ,  G01N21/6428 ,  G01N21/6486 ,  G01N2021/6439 ,  G01N2201/06113 ,  Y10T436/143333

Abstract: Chemical compounds having a high selectivity for double stranded DNA over RNA and single stranded DNA are disclosed. The chemical compounds are stains that become fluorescent upon illumination and interaction with double stranded DNA, but exhibit reduced or no fluorescence in the absence of double stranded DNA. The compounds can be used in a variety of biological applications to qualitatively or quantitatively assay DNA, even in the presence of RNA.

公开(公告)号：US08962853B2

公开(公告)日：2015-02-24

申请号：US13975675

申请日：2013-08-26

Applicant: Life Technologies Corporation

Inventor： Ching-Ying Cheung ,  Diane Gray ,  Stephen Yue

IPC: C07D291/00 ,  C07C211/00 ,  G01N33/58 ,  C07D211/62 ,  C07D295/112 ,  C07D417/06 ,  C07D417/14 ,  C09B23/04 ,  C12Q1/04 ,  C12Q1/18 ,  G01N33/52

CPC classification number: G01N33/1806 ,  C07D211/62 ,  C07D295/112 ,  C07D401/14 ,  C07D417/06 ,  C07D417/14 ,  C09B23/04 ,  C12Q1/04 ,  C12Q1/18 ,  G01N21/643 ,  G01N33/52 ,  G01N33/582 ,  G01N2021/6432

Abstract: Chemical stain compounds containing a fluorophore and a reducible quenching unit are disclosed. The reducible quenching unit quenches the fluorophore while in its oxidized state. Upon reduction, the quenching properties of the quenching unit are diminished or eliminated. The chemical compounds can be used in a variety of applications, including the detection of bacterial cells, monitoring the electron transport chain function of bacterial cells, monitoring the oxidation state of non-biological systems, and assaying the effectiveness of antibacterial or antimicrobial agents.

Abstract translation: 公开了含有荧光团和可还原淬火单元的化学染料化合物。 可还原淬火单元在处于氧化状态时淬灭荧光团。 在还原时，淬火单元的淬火特性减弱或消除。 化合物可用于各种应用，包括检测细菌细胞，监测细菌细胞的电子传递链功能，监测非生物系统的氧化状态，以及测定抗菌剂或抗菌剂的有效性。

公开(公告)号：US20140094608A1

公开(公告)日：2014-04-03

申请号：US14030835

申请日：2013-09-18

Applicant: LIFE TECHNOLOGIES CORPORATION

Inventor： Wai-Yee LEUNG ,  Ching-Ying Cheung ,  Stephen Yue

IPC: C07D498/04 ,  C07D417/06 ,  C07D471/04 ,  C07D209/18

CPC classification number: G01N1/30 ,  A61K41/0057 ,  C07C66/02 ,  C07D209/08 ,  C07D209/12 ,  C07D209/14 ,  C07D209/16 ,  C07D209/18 ,  C07D209/24 ,  C07D209/54 ,  C07D209/60 ,  C07D209/96 ,  C07D401/04 ,  C07D403/06 ,  C07D403/12 ,  C07D403/14 ,  C07D417/06 ,  C07D417/14 ,  C07D471/04 ,  C07D498/04 ,  C07K1/13 ,  C09B23/02 ,  C09B23/06 ,  C09B23/083 ,  C09B23/107 ,  C12Q1/6825 ,  C40B70/00 ,  G01N31/22 ,  G01N33/533 ,  G01N33/535 ,  G01N33/58 ,  G01N33/581 ,  G01N33/582 ,  G01N2001/302 ,  Y10T436/143333

Abstract: Chemically reactive carbocyanine dyes incorporating an indolium ring moiety that is substituted at the 3-position by a reactive group or by a conjugated substance, and their uses, are described. Conjugation through this position results in spectral properties that are uniformly superior to those of conjugates of spectrally similar dyes wherein attachment is at a different position. The invention includes derivative compounds having one or more benzo nitrogens.

Abstract translation: 描述了结合通过反应性基团或共轭物质在3位被取代的吲哚环部分的化学活性碳菁染料及其用途。 通过该位置的共轭导致光谱性质均匀地优于光谱相似的染料的缀合物，其中附着在不同的位置。 本发明包括具有一个或多个苯并氮的衍生化合物。