PEPTIDES WHOSE UPTAKE BY CELLS IS CONTROLLABLE
    31.
    发明申请
    PEPTIDES WHOSE UPTAKE BY CELLS IS CONTROLLABLE 有权
    细胞摄取的肽可以控制

    公开(公告)号:US20110172139A1

    公开(公告)日:2011-07-14

    申请号:US12244602

    申请日:2008-10-02

    摘要: A generic structure for the peptides of the present invention includes A-X-B-C, where C is a cargo moiety, the B portion includes basic amino acids, X is a cleavable linker sequence, and the A portion includes acidic amino acids. The intact structure is not significantly taken up by cells; however, upon extracellular cleavage of X, the B-C portion is taken up, delivering the cargo to targeted cells. Cargo may be, for example, a contrast agent for diagnostic imaging, a chemotherapeutic drug, or a radiation-sensitizer for therapy. Cleavage of X allows separation of A from B, unmasking the normal ability of the basic amino acids in B to drag cargo C into cells near the cleavage event. X is cleaved extracellularly, preferably under physiological conditions. D-amino acids are preferred for the A and B portions, to minimize immunogenicity and nonspecific cleavage by background peptidases or proteases.

    摘要翻译: 本发明的肽的一般结构包括A-X-B-C,其中C是货物部分,B部分包括碱性氨基酸,X是可切割的接头序列,A部分包括酸性氨基酸。 完整结构不被细胞所占据; 然而,在X的细胞外裂解时,B-C部分被吸收,将货物运送到靶细胞。 货物可以是例如用于诊断成像的对比剂,化学治疗药物或用于治疗的放射线敏化剂。 X的裂解允许A与B分离,揭示B中碱性氨基酸的正常能力,将货物C拖入裂解事件附近的细胞。 X在细胞外裂解,优选在生理条件下。 对于A和B部分,D-氨基酸是优选的,以使由背景肽酶或蛋白酶的免疫原性和非特异性切割最小化。

    Peptides whose uptake by cells is controllable
    35.
    发明授权
    Peptides whose uptake by cells is controllable 有权
    细胞摄取的肽是可控的

    公开(公告)号:US07431915B2

    公开(公告)日:2008-10-07

    申请号:US10699562

    申请日:2003-10-31

    IPC分类号: A61K51/00 A61M36/14

    摘要: A generic structure for the peptides of the present invention includes A-X-B-C, where C is a cargo moiety, the B portion includes basic amino acids, X is a cleavable linker sequence, and the A portion includes acidic amino acids. The intact structure is not significantly taken up by cells; however, upon extracellular cleavage of X, the B-C portion is taken up, delivering the cargo to targeted cells. Cargo may be, for example, a contrast agent for diagnostic imaging, a chemotherapeutic drug, or a radiation-sensitizer for therapy. Cleavage of X allows separation of A from B, unmasking the normal ability of the basic amino acids in B to drag cargo C into cells near the cleavage event. X is cleaved extracellularly, preferably under physiological conditions. D-amino acids are preferred for the A and B portions, to minimize immunogenicity and nonspecific cleavage by background peptidases or proteases.

    摘要翻译: 本发明的肽的一般结构包括A-X-B-C,其中C是货物部分,B部分包括碱性氨基酸,X是可切割的接头序列,A部分包括酸性氨基酸。 完整结构不被细胞所占据; 然而,在X的细胞外裂解时,B-C部分被吸收,将货物运送到靶细胞。 货物可以是例如用于诊断成像的对比剂,化学治疗药物或用于治疗的放射线敏化剂。 X的裂解允许A与B分离,揭示B中碱性氨基酸的正常能力,将货物C拖入裂解事件附近的细胞。 X在细胞外裂解,优选在生理条件下。 对于A和B部分,D-氨基酸是优选的,以使由背景肽酶或蛋白酶的免疫原性和非特异性切割最小化。

    Substrates for β-lactamase and uses thereof
    36.
    发明授权
    Substrates for β-lactamase and uses thereof 有权
    β-内酰胺酶底物及其用途

    公开(公告)号:US07157575B2

    公开(公告)日:2007-01-02

    申请号:US10280482

    申请日:2002-10-24

    IPC分类号: C07D501/14

    摘要: Substrates for β-lactamase of the general formula I in which one of X and Y is a fluorescent donor moiety and the other is a quencher (which may or may not re-emit); R′ is selected from the group consisting of H, lower (i.e., alkyl of 1 to about 5 carbon atoms) and (CH2)nOH, in which n is 0 or an integer from 1 to 5; R″ is selected from the group consisting of H, physiologically acceptable metal and ammonium cations, —CHR2OCO(CH2)nCH3, —CHR2OCOC(CH3)3, acylthiomethyl, acyloxy-alpha-benzyl, delta-butyrolactonyl, methoxycarbonyloxymethyl, phenyl, methylsulphinylmethyl, beta-morpholinoethyl, dialkylaminoethyl, acyloxyalkyl, dialkylaminocarbonyloxymethyl and aliphatic, in which R2 is selected from the group consisting of H and lower alkyl; A is selected from the group consisting of S, O, SO, SO2 and CH2; and Z′ and Z″ are linkers for the fluorescent donor and quencher moieties. Methods of assaying β-lactamase activity and monitoring expression in systems using β-lactamase as a reporter gene also are disclosed.

    摘要翻译: 通式I的β-内酰胺酶底物,其中X和Y中的一个是荧光供体部分,另一个是猝灭剂(其可以或不再发射); R'选自H,低级(即1至约5个碳原子的烷基)和(CH 2 CH 2)n OH,其中n是 0或1〜5的整数; R“选自H,生理学上可接受的金属和铵阳离子,-CHR 2 OCO(CH 2)n CH 酰基硫基甲基,酰氧基-α-苄基,三氟甲磺酸酯,三氟甲磺酸酯, 丁基内酰胺,甲氧基羰氧基甲基,苯基,甲基亚磺酰基甲基,β-吗啉代乙基,二烷基氨基乙基,酰氧基烷基,二烷基氨基羰氧基甲基和脂族基,其中R 2选自H和低级烷基; A选自S,O,SO,SO 2和CH 2; Z'和Z“是荧光供体和猝灭剂部分的接头。 公开了使用β-内酰胺酶作为报道基因的体内测定β-内酰胺酶活性和监​​测表达的方法。

    Fluorescent protein sensors for detection of analytes

    公开(公告)号:US07060869B2

    公开(公告)日:2006-06-13

    申请号:US09554000

    申请日:2000-04-20

    IPC分类号: A61K67/027

    摘要: Fluorescent indicators including a binding protein moiety, a donor fluorescent protein moiety, and an acceptor fluorescent protein moiety are described. The binding protein moiety has an analyte-binding region which binds an analyte and causes the indicator to change conformation upon exposure to the analyte. The donor moiety and the acceptor moiety change position relative to each other when the analyte binds to the analyte-binding region. The donor moiety and the acceptor moiety exhibit fluorescence resonance energy transfer when the donor moiety is excited and the distance between the donor moiety and the acceptor moiety is small. The indicators can be used to measure analyte concentrations in samples, such as calcium ion concentrations in cells.

    Emission ratiometric indicators of phosphorylation
    40.
    发明授权
    Emission ratiometric indicators of phosphorylation 失效
    磷酸化的排放比例指标

    公开(公告)号:US06900304B2

    公开(公告)日:2005-05-31

    申请号:US09865291

    申请日:2001-05-24

    摘要: A chimeric phosphorylation indicator is provided. A chimeric phosphorylation indicator can contain a donor molecule, a phosphorylatable domain, a phosphoaminoacid binding domain (PAABD), and an acceptor molecule. A chimeric phosphorylation indicator also can contain a phosphorylatable polypeptide and a fluorescent protein, wherein the phosphorylatable polypeptide is contained within the sequence of the fluorescent protein, or wherein the fluorescent protein is contained within the sequence of the phosphorylatable polypeptide. Also provided are polynucleotides encoding such chimeric phosphorylation indicators, as well as kits containing the indicators or the polynucleotides. In addition, a method of using the chimeric phosphorylation indicators to detect a kinase or phosphatase in a sample is provided.

    摘要翻译: 提供嵌合磷酸化指示剂。 嵌合磷酸化指示剂可以含有供体分子,可磷酸化结构域,磷酸氨基酸结合结构域(PAABD)和受体分子。 嵌合磷酸化指示剂还可含有可磷酸化多肽和荧光蛋白,其中可磷酸化多肽包含在荧光蛋白的序列内,或其中荧光蛋白包含在可磷酸化多肽的序列内。 还提供了编码这种嵌合磷酸化指示剂的多核苷酸,以及含有指示剂或多核苷酸的试剂盒。 此外,提供了使用嵌合磷酸化指示剂来检测样品中的激酶或磷酸酶的方法。