公开(公告)号：US20100113439A1

公开(公告)日：2010-05-06

申请号：US12461318

申请日：2009-08-07

申请人： Mark L. Greenlee ,  Robert Wilkening ,  James Apgar ,  Donald Sperbeck ,  Kenneth J. Wildonger ,  Dongfang Meng ,  Dann L. Parker, JR. ,  Gregory J. Pacofsky ,  Brian H. Heasley ,  Ahmed Mamai ,  Kingsley Nelson

发明人： Mark L. Greenlee ,  Robert Wilkening ,  James Apgar ,  Donald Sperbeck ,  Kenneth J. Wildonger ,  Dongfang Meng ,  Dann L. Parker, JR. ,  Gregory J. Pacofsky ,  Brian H. Heasley ,  Ahmed Mamai ,  Kingsley Nelson

IPC分类号： A61K31/5377 ,  C07D405/04 ,  C07D405/14 ,  C07D413/14 ,  A61P31/10 ,  C07D417/14 ,  A61K31/501 ,  A61K31/497 ,  A61K31/506 ,  A61K31/454 ,  A61K31/427 ,  A61K31/4192 ,  A61K31/4196

CPC分类号： A61K31/343 ,  A01N43/653 ,  A61K31/21 ,  A61K31/41 ,  C07D493/08 ,  C07D519/00

摘要： Novel derivatives of enfumafungin are disclosed herein, along with their pharmaceutically acceptable salts, hydrates and prodrugs. Also disclosed are compositions comprising such compounds, methods of preparing such compounds and methods of using such compounds as antifungal agents and/or inhibitors of (1,3)-β-D-glucan synthase. The disclosed compounds, their pharmaceutically acceptable salts, hydrates and prodrugs, as well as compositions comprising such compounds, salts, hydrates and prodrugs, are useful for treating and/or preventing fungal infections and associated diseases and conditions.

摘要翻译： 本文公开了enfumafungin的新型衍生物及其药学上可接受的盐，水合物和前药。 还公开了包含这种化合物的组合物，制备这些化合物的方法和使用这些化合物作为抗真菌剂和/或（1,3） - ＆bgr-D-葡聚糖合酶抑制剂的方法。 所公开的化合物，其药学上可接受的盐，水合物和前药，以及包含这些化合物，盐，水合物和前药的组合物可用于治疗和/或预防真菌感染和相关疾病和病症。

公开(公告)号：US08188085B2

公开(公告)日：2012-05-29

申请号：US12461318

申请日：2009-08-07

申请人： Mark L. Greenlee ,  Robert Wilkening ,  James Apgar ,  Donald Sperbeck ,  Kenneth J. Wildonger ,  Dongfang Meng ,  Dann L. Parker, Jr. ,  Gregory J. Pacofsky ,  Brian H. Heasley ,  Ahmed Mamai ,  Kingsley Nelson

发明人： Mark L. Greenlee ,  Robert Wilkening ,  James Apgar ,  Donald Sperbeck ,  Kenneth J. Wildonger ,  Dongfang Meng ,  Dann L. Parker, Jr. ,  Gregory J. Pacofsky ,  Brian H. Heasley ,  Ahmed Mamai ,  Kingsley Nelson

IPC分类号： A61K31/41 ,  A61K31/445 ,  A61K31/501 ,  C07D231/02 ,  C07D249/08 ,  C07D401/00 ,  C07D401/02 ,  C07D405/02 ,  C07D405/14

CPC分类号： A61K31/343 ,  A01N43/653 ,  A61K31/21 ,  A61K31/41 ,  C07D493/08 ,  C07D519/00

摘要： Novel derivatives of enfumafungin are disclosed herein, along with their pharmaceutically acceptable salts, hydrates and prodrugs. Also disclosed are compositions comprising such compounds, methods of preparing such compounds and methods of using such compounds as antifungal agents and/or inhibitors of (1,3)-β-D-glucan synthase. The disclosed compounds, their pharmaceutically acceptable salts, hydrates and prodrugs, as well as compositions comprising such compounds, salts, hydrates and prodrugs, are useful for treating and/or preventing fungal infections and associated diseases and conditions.

摘要翻译： 本文公开了enfumafungin的新型衍生物及其药学上可接受的盐，水合物和前药。 还公开了包含这种化合物的组合物，制备这些化合物的方法和使用这些化合物作为抗真菌剂和/或（1,3） - ＆bgr-D-葡聚糖合酶抑制剂的方法。 所公开的化合物，其药学上可接受的盐，水合物和前药，以及包含这些化合物，盐，水合物和前药的组合物可用于治疗和/或预防真菌感染和相关疾病和病症。

公开(公告)号：US08722727B2

公开(公告)日：2014-05-13

申请号：US13058227

申请日：2009-08-10

申请人： Mark L. Greenlee ,  Robert Wilkening ,  James Apgar ,  Donald Sperbeck ,  Kenneth J. Wildonger ,  Dongfang Meng ,  Dann L. Parker, Jr. ,  Ahmed Mamai

发明人： Mark L. Greenlee ,  Robert Wilkening ,  James Apgar ,  Donald Sperbeck ,  Kenneth J. Wildonger ,  Dongfang Meng ,  Dann L. Parker, Jr. ,  Ahmed Mamai

IPC分类号： A61K31/35 ,  C07D311/78

CPC分类号： A61K31/21 ,  A61K31/41 ,  C07D405/04

摘要： Novel derivatives of enfumafungin are disclosed herein, along with' their pharmaceutically acceptable salts, hydrates and prodrugs. Also disclosed are compositions comprising such compounds, methods of preparing such compounds and method of using such compounds as antifungal agents and/or inhibitors of (1,3)-β-D-glucan synthase. The disclosed compounds, their pharmaceutically acceptable salts, hydrates and prodrugs, as well as compositions comprising such compounds, salts, hydrates and prodrugs, are useful for treating and/or preventing fungal infections and associated diseases and conditions.

摘要翻译： 本文公开了enfumafungin的新型衍生物以及“其药学上可接受的盐，水合物和前药”。 还公开了包含这种化合物的组合物，制备这些化合物的方法和使用这些化合物作为抗真菌剂和/或（1,3） - ＆bgr-D-葡聚糖合酶抑制剂的方法。 所公开的化合物，其药学上可接受的盐，水合物和前药，以及包含这些化合物，盐，水合物和前药的组合物可用于治疗和/或预防真菌感染和相关疾病和病症。

公开(公告)号：US20110224228A1

公开(公告)日：2011-09-15

申请号：US13058227

申请日：2009-08-10

申请人： Mark L Greenlee ,  Robert Wilkening ,  James Apgar ,  Donald Sperbeck ,  Kenneth J. Wildonger ,  Dongfang Meng ,  Dann L. Parker, JR. ,  Ahmed Mamai

发明人： Mark L Greenlee ,  Robert Wilkening ,  James Apgar ,  Donald Sperbeck ,  Kenneth J. Wildonger ,  Dongfang Meng ,  Dann L. Parker, JR. ,  Ahmed Mamai

IPC分类号： A61K31/496 ,  C07D405/08 ,  C07D405/14 ,  C07D409/14 ,  A61K31/41 ,  A61K31/454 ,  A61P31/10

CPC分类号： A61K31/21 ,  A61K31/41 ,  C07D405/04

摘要： Novel derivatives of enfumafungin are disclosed herein, along with' their pharmaceutically acceptable salts, hydrates and prodrugs. Also disclosed are compositions comprising such compounds, methods of preparing such compounds and method of using such compounds as antifungal agents and/or inhibitors of (1,3)-β-D-glucan synthase. The disclosed compounds, their pharmaceutically acceptable salts, hydrates and prodrugs, as well as compositions comprising such compounds, salts, hydrates and prodrugs, are useful for treating and/or preventing fungal infections and associated diseases and conditions.

摘要翻译： 本文公开了enfumafungin的新型衍生物以及“其药学上可接受的盐，水合物和前药”。 还公开了包含这种化合物的组合物，制备这些化合物的方法和使用这些化合物作为抗真菌剂和/或（1,3） - ＆bgr-D-葡聚糖合酶抑制剂的方法。 所公开的化合物，其药学上可接受的盐，水合物和前药，以及包含这些化合物，盐，水合物和前药的组合物可用于治疗和/或预防真菌感染和相关疾病和病症。

公开(公告)号：US20130036517A1

公开(公告)日：2013-02-07

申请号：US13508234

申请日：2010-11-05

申请人： James Apgar ,  Philip Lessard ,  R. Michael Raab ,  Binzhang Shen ,  Gabor Lazar ,  Humberto de la Vega

发明人： James Apgar ,  Philip Lessard ,  R. Michael Raab ,  Binzhang Shen ,  Gabor Lazar ,  Humberto de la Vega

IPC分类号： C12N9/24 ,  C07K16/40 ,  A01H5/00 ,  C12N9/42 ,  C12N15/56

CPC分类号： C12Y302/01004 ,  C12N9/2437 ,  C12N9/248 ,  C12N15/8216 ,  C12N15/8246 ,  C12Y302/01008

摘要： A method of predicting an intein insertion site in a protein that will lead to a switching phenotype is provided. The method includes identifying a plurality of C/T/S sites within the protein; selecting from the plurality of C/T/S/ sites those that are ranked 0.75 or higher by a support vector machine, within ten angstroms of the active site of the protein, and at or near a loop-β-sheet junction or a loop-α-helix junction. A method of controlling protein activity and hosts including proteins with controlled activity are also provided. Also, intein modified proteins and plants containing intein modified proteins are provided.

摘要翻译： 提供了一种预测蛋白质中的内含肽插入位点将导致切换表型的方法。 该方法包括鉴定蛋白内的多个C / T / S位点; 从多个C / T / S /位点中选择由支持向量机排列为0.75或更高的那些，在蛋白质的活性位点的10埃内，以及在环 - 环α螺旋结。 还提供了控制蛋白质活性的方法和包含具有受控活性的蛋白质的宿主。 此外，提供了内含肽修饰的蛋白质和含有内含肽修饰的蛋白质的植物。

公开(公告)号：US10407742B2

公开(公告)日：2019-09-10

申请号：US13508156

申请日：2010-11-05

申请人： Binzhang Shen ,  Gabor Lazar ,  Humberto de la Vega ,  Philip Lessard ,  R. Michael Raab ,  James Apgar

发明人： Binzhang Shen ,  Gabor Lazar ,  Humberto de la Vega ,  Philip Lessard ,  R. Michael Raab ,  James Apgar

IPC分类号： C12N9/42 ,  C12N9/24 ,  C12N15/82

摘要： Intein modified proteins, isolated nucleic acids encoding intein modified proteins, fragments of intein modified proteins, isolated nucleic acids encoding fragments of intein modified proteins, transgenic plants containing any of the foregoing, and antibodies recognizing epitopes on intein modified proteins are provided.

公开(公告)号：US20110111442A1

公开(公告)日：2011-05-12

申请号：US12590444

申请日：2009-11-06

申请人： Binzhang Shen ,  Gabor Lazar ,  Humberto de la Vega ,  James Apgar ,  Philip Lessard ,  R. Michael Raab

发明人： Binzhang Shen ,  Gabor Lazar ,  Humberto de la Vega ,  James Apgar ,  Philip Lessard ,  R. Michael Raab

IPC分类号： C12Q1/34 ,  C12N9/14 ,  C12N9/42 ,  C12N15/63 ,  A01H5/00

CPC分类号： C12N9/2482 ,  C12N9/2437 ,  C12N9/248 ,  C12N15/8216 ,  C12N15/8241 ,  C12N15/8246 ,  C12Y302/01004 ,  C12Y302/01008

摘要： A method of predicting an intein insertion site in a protein that will lead to a switching phenotype is provided. The method includes identifying a plurality of C/T/S sites within the protein; selecting from the plurality of C/T/S/ sites those that are ranked 0.75 or higher by a support vector machine, within ten angstroms of the active site of the protein, and at or near a loop-β-sheet junction or a loop-α-helix junction. A method of controlling protein activity and hosts including proteins with controlled activity are also provided. Also, intein modified proteins and plants containing intein modified proteins are provided.

摘要翻译： 提供了一种预测蛋白质中的内含肽插入位点将导致切换表型的方法。 该方法包括鉴定蛋白内的多个C / T / S位点; 从多个C / T / S /位点中选择由支持向量机排列为0.75或更高的那些，在蛋白质的活性位点的10埃内，以及在环 - 环α螺旋结。 还提供了控制蛋白质活性的方法和包含具有受控活性的蛋白质的宿主。 此外，提供了内含肽修饰的蛋白质和含有内含肽修饰的蛋白质的植物。

公开(公告)号：US09464333B2

公开(公告)日：2016-10-11

申请号：US13508234

申请日：2010-11-05

申请人： James Apgar ,  Philip Lessard ,  R. Michael Raab ,  Binzhang Shen ,  Gabor Lazar ,  Humberto de la Vega

发明人： James Apgar ,  Philip Lessard ,  R. Michael Raab ,  Binzhang Shen ,  Gabor Lazar ,  Humberto de la Vega

IPC分类号： C12N9/48 ,  C12N9/42 ,  C12N9/24 ,  C12N15/82

CPC分类号： C12Y302/01004 ,  C12N9/2437 ,  C12N9/248 ,  C12N15/8216 ,  C12N15/8246 ,  C12Y302/01008

摘要： A method of predicting an intein insertion site in a protein that will lead to a switching phenotype is provided. The method includes identifying a plurality of C/T/S sites within the protein; selecting from the plurality of C/T/S/ sites those that are ranked 0.75 or higher by a support vector machine, within ten angstroms of the active site of the protein, and at or near a loop-β-sheet junction or a loop-α-helix junction. A method of controlling protein activity and hosts including proteins with controlled activity are also provided. Also, intein modified proteins and plants containing intein modified proteins are provided.

摘要翻译： 提供了一种预测蛋白质中的内含肽插入位点将导致切换表型的方法。 该方法包括鉴定蛋白内的多个C / T / S位点; 从多个C / T / S /位点中选择由支持向量机排列为0.75或更高的那些，在蛋白质的活性位点的10埃内，以及在环-β-片结或环 -α-螺旋结。 还提供了控制蛋白质活性的方法和包含具有受控活性的蛋白质的宿主。 此外，提供了内含肽修饰的蛋白质和含有内含肽修饰的蛋白质的植物。

公开(公告)号：US09388422B2

公开(公告)日：2016-07-12

申请号：US13818928

申请日：2011-08-23

申请人： Binzhang Shen ,  James Apgar ,  Oleg Bougri ,  R. Michael Raab

发明人： Binzhang Shen ,  James Apgar ,  Oleg Bougri ,  R. Michael Raab

IPC分类号： C12N9/24 ,  A01H5/00 ,  A01H5/10 ,  C12N15/82 ,  C12N15/05 ,  C12P19/14

CPC分类号： C12N15/8243 ,  C12N9/248 ,  C12N9/2482 ,  C12N15/8216 ,  C12N15/8246 ,  C12P19/14 ,  C12Y302/01008

摘要： In planta consolidated bioprocessing has the advantages of decreasing biomass pretreatment costs, utilizing excess plant protein production capacity for enzyme production, and decreasing mass transfer resistance of enzyme diffusion to its substrate. However, in planta expression of cell wall degrading (CWD) enzymes often leads to detrimental plant phenotypes that impact crop yield. To provide in planta CWD enzyme activity without any adverse phenotype, a thermostable xylanase, XynB (EC 3.2.1.8), was engineered with a thermoregulated intein, Tth-HB27 DnaE-1 (Tth intein), that controls its hydrolytic activity through conditional intein splicing. Maize plants expressing the heat inducible Tth intein-modified XynB developed normally, yet possessed enhanced post harvest glucose production from dried corn stover. Expression of CWD enzymes as dormant, intein-modified proteins that can be activated by heat treatment after harvest provides the basis for developing a novel cellulosic processing trait in plants.

摘要翻译： 在植物中，综合生物处理具有降低生物量预处理成本，利用植物蛋白生产过剩的酶生产能力，降低酶扩散对其底物的传质阻力的优点。 然而，在植物表达的细胞壁降解（CWD）酶通常导致有害的植物表型影响作物产量。 为了提供没有任何不良表型的植物CWD酶活性，用热调节的内含肽Tth-HB27DnaE-1（第T个内含肽）设计热稳定的木聚糖酶XynB（EC 3.2.1.8），其通过条件内含肽来控制其水解活性 拼接。 表达热诱导性Tth内含肽修饰的XynB的玉米植物正常发育，但具有来自干玉米秸秆的后收获葡萄糖产量的增强。 CWD酶作为休眠后的内含肽修饰蛋白质的表达，可以在收获后通过热处理活化，为开发植物中新型纤维素加工性状提供依据。

公开(公告)号：US20130007919A1

公开(公告)日：2013-01-03

申请号：US13508156

申请日：2010-11-05

申请人： Binzhang Shen ,  Gabor Lazar ,  Humberto de la Vega ,  Philip Lessard ,  R. Michael Raab ,  James Apgar

发明人： Binzhang Shen ,  Gabor Lazar ,  Humberto de la Vega ,  Philip Lessard ,  R. Michael Raab ,  James Apgar

IPC分类号： C12N9/42 ,  A01H5/00 ,  C07K16/40 ,  C12N15/52

CPC分类号： C12Y302/01004 ,  C12N9/2437 ,  C12N9/248 ,  C12N15/8216 ,  C12N15/8246 ,  C12N15/8257 ,  C12Y302/01008

摘要： Intein modified proteins, isolated nucleic acids encoding intein modified proteins, fragments of intein modified proteins, isolated nucleic acids encoding fragments of intein modified proteins, transgenic plants containing any of the foregoing, and antibodies recognizing epitopes on intein modified proteins are provided

摘要翻译： 提供了编码内含肽修饰蛋白质的分离核酸，内含肽修饰蛋白质片段，编码内含肽修饰蛋白质片段的分离核酸，含有前述内容物的转基因植物，以及识别内含肽修饰蛋白质上的抗原决定簇的抗体。