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    Previns as specific inhibitors and therapeutic agents for Botulinum toxin B and Tetanus neurotoxins
    1.
    发明授权
    Previns as specific inhibitors and therapeutic agents for Botulinum toxin B and Tetanus neurotoxins 失效
    前列腺素作为肉毒杆菌毒素B和破​​伤丹神经毒素的特异性抑制剂和治疗剂

    公开(公告)号：US06573244B1

    公开(公告)日：2003-06-03

    申请号：US09570022

    申请日：2000-05-12

    申请人： Richard K. Gordon ,  Debbie R. Moorad ,  Bhupendra P. Doctor ,  Gregory E. Garcia

    发明人： Richard K. Gordon ,  Debbie R. Moorad ,  Bhupendra P. Doctor ,  Gregory E. Garcia

    IPC分类号： A61K3800

    CPC分类号： C07K7/06 ,  A61K38/00 ,  C07K7/08 ,  C07K7/22 ,  C07K14/8146

    摘要： The compounds of the invention are generally described by the formula: B1Z*2B3Z*4X*5Q6F7X8X9X10X11  (1), B1X2X3X4X5Q6F7X8X9X10X11  (2), or B1X2B3X4Z5Q6F7Z*8X9X10X11  (3) and the salts, esters, amides, and acyl forms thereof. Each position represented by a letter indicates a single amino acid residue: B is a basic or polar/large amino acid or a modified form thereof; X is a small or hydrophobic amino acid or a modified form thereof; X* is a small or polar/large amino acid or a modified form thereof; Z is a polar/large or hydrophobic amino acid or a modified form thereof; Z* is Proline or a polar/large or hydrophobic amino acid or a modified form thereof. As described below, one or more of the peptide linkages between the amino acid residues may be replaced by a peptide linkage mimic. These compounds may be used as molecular building blocks to create compounds that are optimized for inhibiting the protease activity of Botulinum B and tetanus toxins.

    摘要翻译： 本发明的化合物通常用下式描述：或其盐，酯，酰胺及其酰基形式。 由字母表示的每个位置表示单个氨基酸残基：B是碱性或极性/大氨基酸或其修饰形式; X是小或疏水性氨基酸或其修饰形式; X *是小或极/大氨基酸或其修饰形式; Z是极性/大或疏水性氨基酸或其修饰形式; Z *是脯氨酸或极性/大或疏水性氨基酸或其修饰形式。 如下所述，氨基酸残基之间的一个或多个肽键可以被肽键模拟物代替。这些化合物可以用作分子结构单元以产生针对抑制肉毒杆菌B和破伤风的蛋白酶活性而优化的化合物 毒素

    Buforin I as a specific inhibitor and therapeutic agent for botulinum toxin B and tetanus neurotoxins
    2.
    发明授权
    Buforin I as a specific inhibitor and therapeutic agent for botulinum toxin B and tetanus neurotoxins 失效
    Buforin I作为特异性抑制剂和肉毒杆菌毒素B和破​​伤风神经毒素的治疗剂

    公开(公告)号：US06713444B1

    公开(公告)日：2004-03-30

    申请号：US09570023

    申请日：2000-05-12

    申请人： Gregory E. Garcia ,  Richard K. Gordon ,  Debbie R. Moorad ,  Bhupendra P. Doctor

    发明人： Gregory E. Garcia ,  Richard K. Gordon ,  Debbie R. Moorad ,  Bhupendra P. Doctor

    IPC分类号： A61K3800

    CPC分类号： C07K14/8146 ,  A61K38/00

    摘要： The compounds of the invention are generally described by the formula: X1X2B3X4B5X*6X7X8 B9X10B11X12B13X14 B15X16B17X*18X*19B20 X21X22X23Q24F25Z*26X27 X28B29X30B31B32X33X34 B35B36X37Z38Z39  (1) and the salts, esters, amides, and acyl forms thereof. Up to 15 amino acids may be truncated from the N-terminus and up to 6 amino acids may be truncated from the C-terminus. Each position represented by a letter indicates a single amino acid residue wherein B is a basic or polar/large amino acid or a modified form thereof; X is a small or hydrophobic amino acid or a modified form thereof; X* is a small or polar/large amino acid or a modified form thereof; Z is a polar/large or hydrophobic amino acid or a modified form thereof; Z* is Proline or a polar/large or hydrophobic amino acid or a modified form thereof. These compounds may be used to inhibit the protease activity of Botulinum B and tetanus toxins.

    摘要翻译： 本发明的化合物通常用下式描述：及其盐，酯，酰胺及其酰基形式。 可以从N末端截断至多15个氨基酸，并且可以从C末端截断至多6个氨基酸。 由字母表示的每个位置表示单个氨基酸残基，其中B是碱性或极性/大氨基酸或其修饰形式; X是小或疏水性氨基酸或其修饰形式; X *是小或极/大氨基酸或其修饰形式; Z是极性/大或疏水性氨基酸或其修饰形式; Z *是脯氨酸或极性/大或疏水性氨基酸或其修饰形式。 这些化合物可用于抑制肉毒杆菌B和破伤风毒素的蛋白酶活性。

    Previns as specific inhibitors and therapeutic agents for botulinum toxin B and tetanus neurotoxins
    3.
    发明授权
    Previns as specific inhibitors and therapeutic agents for botulinum toxin B and tetanus neurotoxins 失效
    前列腺素作为肉毒杆菌毒素B和破​​伤风神经毒素的特异性抑制剂和治疗剂

    公开(公告)号：US07235521B1

    公开(公告)日：2007-06-26

    申请号：US09979101

    申请日：2000-05-15

    申请人： Richard K. Gordon ,  Deborah R. Moorad ,  Bhupendra P. Doctor ,  Gregory E. Garcia

    发明人： Richard K. Gordon ,  Deborah R. Moorad ,  Bhupendra P. Doctor ,  Gregory E. Garcia

    IPC分类号： A61K38/00

    CPC分类号： C12Q1/37 ,  G01N2333/95 ,  G01N2500/00

    摘要： The compounds of the invention are generally described by the formula (1): B1Z*2B3Z*4X*5Q6F7X8X9X10X11, (2): B1X2X3X4X5Q6F7X8X9X10X11, or (3): B1X2B3X4Z5Q6F7Z8X9X10X11 and the salts, esters, amides, and acyl forms thereof. Each position represented by a letter indicates a single amino acid residue: B is a basic or polar/large amino acid or a modified form thereof; X is a small or hydrophobic amino acid or a modified form thereof; X* is a small or polar/large amino acid or a modified form thereof; Z is a polar/large or hydrophobic amino acid or a modified form thereof; Z* is Proline or a polar/large or hydrophobic amino acid or a modified form thereof. As described below, one or more of the peptide linkages between the amino acid residues may be replaced by a peptide linkage mimic. These compounds may be used as molecular building blocks to create compounds that are optimized for inhibiting the protease activity of Botulinum B and tetanus toxins.

    摘要翻译： 本发明的化合物通常由式（1）描述：B 1 Z * 2 B 3 Z * 4 < 5×6×6×6××××××××××××××××××××××××××××××××××××××××××< （2）：B 1 X 2 X 3 X 2 X 2 X 3 5 5 5 或（3）：B 1 X 2 B 3 3 5 X 5 5 5 它们的盐，酯，酰胺和酰基形式。 由字母表示的每个位置表示单个氨基酸残基：B是碱性或极性/大氨基酸或其修饰形式; X是小或疏水性氨基酸或其修饰形式; X *是小或极/大氨基酸或其修饰形式; Z是极性/大或疏水性氨基酸或其修饰形式; Z *是脯氨酸或极性/大或疏水性氨基酸或其修饰形式。 如下所述，氨基酸残基之间的一个或多个肽键可以被肽键模拟物代替。 这些化合物可用作分子结构单元以产生针对抑制肉毒杆菌B和破伤风毒素的蛋白酶活性而优化的化合物。

    Detoxification with sponges or foams containing plurality of enzymes and encapsulated indicator
    6.
    发明授权
    Detoxification with sponges or foams containing plurality of enzymes and encapsulated indicator 有权
    使用含有多种酶和包封指示剂的海绵或泡沫进行解毒

    公开(公告)号：US06541230B1

    公开(公告)日：2003-04-01

    申请号：US09559396

    申请日：2000-04-26

    申请人： Richard K. Gordon ,  Bhupendra P. Doctor

    发明人： Richard K. Gordon ,  Bhupendra P. Doctor

    IPC分类号： C12N1118

    CPC分类号： C12N11/08 ,  C08G18/10 ,  C08G18/6446 ,  C08G2101/00 ,  C08G2101/0083 ,  C12N11/00 ,  C08G18/64 ,  C08G18/302

    摘要： A reusable sponge or foam made of a polymer such as polyurethane is prepared containing a plurality of different enzymes or a cross-linked complex of the plurality of enzymes for detoxification of a diverse array of hazardous chemicals such as organophosphorus and/or organosulfur compounds. The plurality of enzymes include enzymes selected from acetylcholinesterase, butyrylcholinesterase, triesterase, pseudocholinesterase, choline oxidase, peroxidase, organophosphate hydrolase, phosphotriesterase, paraoxonase and laccase. A preferred mixture of enzymes contains organophosphate hydrolase and acetylcholinesterase or butyrylcholinesterase. The sponge or foam may additionally contain carbon, an enzyme reactivation compound and/or an indicator for measuring capacity for detoxification. The indicator can be fluorescent, chemiluminescent or visible chromogen or an electrode, and be encapsulated in a liposome or crushable packet. The sponge or foam may be color-coded to indicate specific chemical detoxified, or to indicate enzymatic concentration, activity and/or remaining shelf-life. A kit is formed containing the sponge or foam and the compound for enzyme reactivation.

    摘要翻译： 制备由诸如聚氨酯的聚合物制成的可重复使用的海绵或泡沫，其含有多种不同酶或多种酶的交联复合物，用于解毒各种危险化学物质如有机磷和/或有机硫化合物。 多种酶包括选自乙酰胆碱酯酶，丁酰胆碱酯酶，三酯酶，假胆碱酯酶，胆碱氧化酶，过氧化物酶，有机磷酸盐水解酶，磷酸三酯酶，对氧磷酶和漆酶的酶。 酶的优选混合物含有有机磷酸酯水解酶和乙酰胆碱酯酶或丁酰胆碱酯酶。 海绵或泡沫可另外含有碳，酶再活化化合物和/或用于测定排毒能力的指标。 指示剂可以是荧光，化学发光或可见的色原体或电极，并且被包封在脂质体或可压碎的包中。 海绵或泡沫可以是颜色编码的，以指示特定的化学解毒，或指示酶浓度，活性和/或保留的保质期。 形成包含海绵或泡沫和酶再活化的化合物的试剂盒。

    Assay for detecting, measuring and monitoring the activities and concentrations of proteins and methods of use thereof
    9.
    发明授权
    Assay for detecting, measuring and monitoring the activities and concentrations of proteins and methods of use thereof 失效

    公开(公告)号：US06746850B2

    公开(公告)日：2004-06-08

    申请号：US09848370

    申请日：2001-05-04

    申请人： Shawn R. Feaster ,  Richard K. Gordon ,  Bhupendra P. Doctor

    发明人： Shawn R. Feaster ,  Richard K. Gordon ,  Bhupendra P. Doctor

    IPC分类号： C12Q146

    CPC分类号： C12Q1/005 ,  C12Q1/46 ,  G01N33/557 ,  G01N33/567

    摘要： An assay for detecting, measuring, or monitoring the activity or concentration of at least two proteins that have similar or overlapping properties is disclosed. The assay comprises first determining the sensitivity coefficients of the substrates for each of the proteins in which the concentrations are to be determined. This method may be used for detecting, measuring, or monitoring the activity and concentration of AChE, BChE, or both in a test sample which test sample may be whole and unprocessed blood or tissue. Also disclosed are methods of using the assay to detect a subject's exposure to an agent which affects cholinesterase, determine the efficacy or progress of a treatment, determine the amount of protection provided against exposure to an agent which affects cholinesterase, or both, screen a subject for having a drug sensitivity or a particular disease, detect a change in red blood cell count of a subject, determine whether a candidate compound affects cholinesterase. Also disclosed are devices and kits for detecting, measuring, or monitoring the activities and concentrations of AChE, BChE, or both.