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    Fluorescent quenching detection reagents and methods
    6.
    发明授权
    Fluorescent quenching detection reagents and methods 有权
    荧光猝灭检测试剂及方法

    公开(公告)号：US06699975B2

    公开(公告)日：2004-03-02

    申请号：US10093769

    申请日：2002-03-07

    申请人： Michael W. Reed ,  Eugeny Alexander Lukhtanov ,  Alexander A. Gall ,  Robert O. Dempcy

    发明人： Michael W. Reed ,  Eugeny Alexander Lukhtanov ,  Alexander A. Gall ,  Robert O. Dempcy

    IPC分类号： C07C24500

    CPC分类号： C07D519/00 ,  C07B2200/11 ,  C07C245/08 ,  C07F9/2408 ,  C07F9/572 ,  C07F9/65522 ,  C07F9/6561 ,  C07H21/00 ,  C09B29/0813 ,  C12Q1/6818 ,  C40B40/00 ,  C12Q2565/1025 ,  C12Q2521/319

    摘要： Oligonucleotide-fluorophore-quencher conjugates wherein the fluorophore moiety has emission wavelengths in the range of about 300 to about 800 nm, and or where the quencher includes a substituted 4-(phenyldiazenyl)phenylamine structure provide improved signal to noise ratios and other advantageous characteristics in hybridization and related assays. The oligonucleotide-fluorophore-quencher conjugates can be synthesized by utilizing novel phosphoramidite reagents that incorporate the quencher moiety based on the substituted 4-(phenyidiazenyl)phenylamine structure, and or novel phosphoramidite reagents that incorporate a fluorophore moiety based on the substituted coumarin, substituted 7-hydroxy-3H-phenoxazin-3-one, or substituted 5,10-dihydro-10-[phenyl]pyrido[2,3-d;6,5-d′]dipyrimidine-2,4,6,8-(1H,3H,7H,9H,10H)-tetrone structure. Oligonucleotide-fluorophore-quencher-minor groove binder conjugates including a pyrrolo[4,5-e]indolin-7-yl}carbonyl) pyrrolo[4,5-e]indolin-7-yl]carbonyl}pyrrolo[4,5-e]indoline-7-carboxylate (DPI3) moiety as the minor groove binder and the substituted 4-(phenyldiazenyl)phenylamine moiety as the quencher, were synthesized and have substantially improved hybridization and signal to noise ratio properties.

    摘要翻译： 寡核苷酸 - 荧光团 - 猝灭剂缀合物，其中荧光团部分具有在约300至约800nm范围内的发射波长，或者其中猝灭剂包括取代的4-（苯基二氮烯基）苯胺结构提供改善的信噪比和其它有利特征 杂交和相关测定。 寡核苷酸 - 荧光团 - 猝灭剂缀合物可以通过利用基于取代的4-（苯基亚基）苯胺结构的掺入猝灭剂部分的新型亚磷酰胺试剂和/或掺入基于取代香豆素的荧光团部分的新型亚磷酰胺试剂来合成，取代7 - 羟基-3H-吩恶嗪-3-酮或取代的5,10-二氢-10- [苯基]吡啶并[2,3-d; 6,5-d']二嘧啶-2,4,6,8-（ 1H，3H，7H，9H，10H） - 四酮结构。 吡咯并[4,5-e]二氢吲哚-7-基}羰基）吡咯并[4,5-e]二氢吲哚-7-基]羰基}吡咯并[4,5- e]二氢吲哚-7-羧酸酯（DPI 3）部分作为次槽粘合剂和取代的4-（苯基二氮烯基）苯胺部分作为猝灭剂，并且具有显着改善的杂交和信噪比性质。

    Peptide linkers for improved oligonucleotide delivery
    7.
    发明授权
    Peptide linkers for improved oligonucleotide delivery 失效
    用于改进寡核苷酸递送的肽接头

    公开(公告)号：US5574142A

    公开(公告)日：1996-11-12

    申请号：US991199

    申请日：1992-12-15

    申请人： Rich B. Meyer, Jr. ,  Alexander A. Gall ,  Michael W. Reed

    发明人： Rich B. Meyer, Jr. ,  Alexander A. Gall ,  Michael W. Reed

    IPC分类号： A61K47/48 ,  C07H21/04 ,  C07K4/00

    CPC分类号： A61K47/48092 ,  A61K47/48246 ,  A61K47/48415 ,  A61K47/48715

    摘要： A covalently linked conjugate of an oligonucleotide (ODN) with a peptide and a carrier or targeting ligand (ODN-peptide-carrier) includes a therapeutic oligonucleotide which is capable of selectively binding to a target sequence of DNA, RNA or protein inside a target cell. The ODN is covalently linked to a peptide which is capable of being cleaved by proteolytic enzymes inside the target cell. The peptide, in turn is covalently linked to a carrier or targeting ligand moiety which facilitates delivery of the entire ODN-peptide-carrier conjugate into the cell, and preferably into a specific target tissue type. Inside the cell, the peptide is cleaved, releasing the ODN which, by binding to the target DNA, RNA or protein sequence, brings about a beneficial result.

    摘要翻译： 寡核苷酸（ODN）与肽和载体或靶向配体（ODN-肽 - 载体）的共价连接的缀合物包括能够选择性地结合目标细胞内的DNA，RNA或蛋白质的靶序列的治疗性寡核苷酸 。 ODN与能够被靶细胞内的蛋白水解酶切割的肽共价连接。 肽又与共价连接到载体或靶向配体部分，其有助于将整个ODN-肽 - 载体缀合物递送到细胞中，优选进入特定的靶组织类型。 在细胞内，肽被切割，释放ODN，其通过结合靶DNA，RNA或蛋白质序列带来有益的结果。