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1. 发明授权

US08431121B2 Specifically targeted catalytic antagonists and uses thereof 失效
标题翻译：特异性靶向催化拮抗剂及其用途
公开(公告)号：US08431121B2
公开(公告)日：2013-04-30
申请号：US12953378
申请日：2010-11-23
申请人： Benjamin G. Davis , John Bryan Jones , Richard R. Bott , Karl John Sanford , David Aaron Estell
发明人： Benjamin G. Davis , John Bryan Jones , Richard R. Bott , Karl John Sanford , David Aaron Estell
IPC分类号： A61K38/48
CPC分类号： B82Y5/00 , A61K47/51 , A61K47/665 , A61K47/6898
摘要： This invention provides chimeric molecules that are catalytic antagonists of a target molecule. The catalytic antagonists of this invention preferably comprise a targeting moiety attached to an enzyme that degrades the molecule specifically bound by the targeting moiety. The catalytic antagonists of this invention thus bind to a target recognized by the targeting moiety (e.g., a receptor) the enzyme component of the chimera then degrades all or part of the target. This typically results in a reduction or loss of activity of the target and release of the chimeric molecule. The chimeric molecule is then free to attack and degrade another target molecule.
摘要翻译：本发明提供作为靶分子的催化拮抗剂的嵌合分子。本发明的催化拮抗剂优选包含与降解由靶向部分特异性结合的分子的酶连接的靶向部分。因此，本发明的催化拮抗剂与靶向部分识别的靶（例如受体）结合，嵌合体的酶组分然后降解靶的全部或部分。这通常导致靶的活性降低或丧失，并释放嵌合分子。然后嵌合分子可以自由地攻击和降解另一个靶分子。

2. 发明申请

US20120295329A1 CHEMICALLY MODIFIED MUTANT SERINE HYDROLASES SHOW IMPROVED CATALYTIC ACTIVITY AND CHIRAL SELECTIVITY 失效
公开(公告)号：US20120295329A1
公开(公告)日：2012-11-22
申请号：US13561257
申请日：2012-07-30
申请人： John Bryan Jones , Michael Dickman , Richard C. Lloyd
发明人： John Bryan Jones , Michael Dickman , Richard C. Lloyd
IPC分类号： C12N9/14 , C12N9/50
CPC分类号： C12N9/54
摘要： This invention provides novel chemically modified mutant serine hydrolases that catalyze a transamidation and/or a transpeptidation and/or a transesterification reaction. The modified serine hydrolases have one or more amino acid residues in a subsite replaced with a cysteine, wherein the cysteine is modified by replacing the thiol hydrogen in the cysteine with a substituent group providing a thiol side chain comprising a moiety selected from the group consisting of a polar aromatic substituent, an alkyl amino group with a positive charge, and a glycoside. In particularly preferred embodiments, the substitutents include an oxazolidinone, a C1 to C15 alkyl amino group with a positive charge, or a glycoside.

3. 发明申请

US20120156721A1 CHEMICALLY MODIFIED MUTANT SERINE HYDROLASES SHOW IMPROVED CATALYTIC ACTIVITY AND CHIRAL SELECTIVITY 审中-公开
标题翻译：化学改性的突变丝氨酸水解酶改善了催化活性和CHIRAL选择性
公开(公告)号：US20120156721A1
公开(公告)日：2012-06-21
申请号：US13405083
申请日：2012-02-24
申请人： John Bryan Jones , Michael Dickman , Richard C. Lloyd
发明人： John Bryan Jones , Michael Dickman , Richard C. Lloyd
IPC分类号： C12N9/50 , C12P7/40 , C12S99/00 , C12P13/04 , C12N9/56 , C12P21/06
CPC分类号： C12N9/54
摘要： This invention provides novel chemically modified mutant serine hydrolases that catalyze a transamidation and/or a transpeptidation and/or a transesterification reaction. The modified serine hydrolases have one or more amino acid residues in a subsite replaced with a cysteine, wherein the cysteine is modified by replacing the thiol hydrogen in the cysteine with a substituent group providing a thiol side chain comprising a moiety selected from the group consisting of a polar aromatic substituent, an alkyl amino group with a positive charge, and a glycoside. In particularly preferred embodiments, the substitutents include an oxazolidinone, a C1 to C15 alkyl amino group with a positive charge, or a glycoside.
摘要翻译：本发明提供新颖的化学修饰的突变丝氨酸水解酶，其催化转酰胺化和/或转肽化和/或酯交换反应。修饰的丝氨酸水解酶在被半胱氨酸替代的子位点中具有一个或多个氨基酸残基，其中通过用提供包含选自以下的部分的硫醇侧链的取代基取代半胱氨酸中的巯基氢来修饰半胱氨酸。极性芳族取代基，带正电荷的烷基氨基和糖苷。在特别优选的实施方案中，取代基包括恶唑烷酮，带正电荷的C1至C15烷基氨基或糖苷。

4. 发明授权

US08148128B2 Chemically modified mutant serine hydrolases show improved catalytic activity and chiral selectivity 有权
标题翻译：化学修饰的突变丝氨酸水解酶显示出改进的催化活性和手性选择性
公开(公告)号：US08148128B2
公开(公告)日：2012-04-03
申请号：US12234399
申请日：2008-09-19
申请人： John Bryan Jones , Michael Dickman , Richard C. Lloyd
发明人： John Bryan Jones , Michael Dickman , Richard C. Lloyd
IPC分类号： C12N9/52 , C12N9/54 , C12N15/57 , C12N15/75
CPC分类号： C12N9/54
摘要： This invention provides novel chemically modified mutant serine hydrolases that catalyze a transamidation and/or a transpeptidation and/or a transesterification reaction. The modified serine hydrolases have one or more amino acid residues in a subsite replaced with a cysteine, wherein the cysteine is modified by replacing the thiol hydrogen in the cysteine with a substituent group providing a thiol side chain comprising a moiety selected from the group consisting of a polar aromatic substituent, an alkyl amino group with a positive charge, and a glycoside. In particularly preferred embodiments, the substitutents include an oxazolidinone, a C1 to C15 alkyl amino group with a positive charge, or a glycoside.
摘要翻译：本发明提供新颖的化学修饰的突变丝氨酸水解酶，其催化转酰胺化和/或转肽化和/或酯交换反应。修饰的丝氨酸水解酶在被半胱氨酸替代的子位点中具有一个或多个氨基酸残基，其中通过用提供包含选自以下的部分的硫醇侧链的取代基取代半胱氨酸中的巯基氢来修饰半胱氨酸。极性芳族取代基，带正电荷的烷基氨基和糖苷。在特别优选的实施方案中，取代基包括恶唑烷酮，带正电荷的C1至C15烷基氨基或糖苷。

5. 发明申请

US20090075329A1 CHEMICALLY MODIFIED MUTANT SERINE HYDROLASES SHOW IMPROVED CATALYTIC ACTIVITY AND CHIRAL SELECTIVITY 有权
标题翻译：化学改性的突变丝氨酸水解酶改善了催化活性和CHIRAL选择性
公开(公告)号：US20090075329A1
公开(公告)日：2009-03-19
申请号：US12234399
申请日：2008-09-19
申请人： John Bryan Jones , Michael Dickman , Richard C. Lloyd
发明人： John Bryan Jones , Michael Dickman , Richard C. Lloyd
IPC分类号： C12N9/56 , C12N9/50 , C12P21/00 , C12P7/62 , C12P13/02 , C12P13/04
CPC分类号： C12N9/54
摘要： This invention provides novel chemically modified mutant serine hydrolases that catalyze a transamidation and/or a transpeptidation and/or a transesterification reaction. The modified serine hydrolases have one or more amino acid residues in a subsite replaced with a cysteine, wherein the cysteine is modified by replacing the thiol hydrogen in the cysteine with a substituent group providing a thiol side chain comprising a moiety selected from the group consisting of a polar aromatic substituent, an alkyl amino group with a positive charge, and a glycoside. In particularly preferred embodiments, the substitutents include an oxazolidinone, a C1 to C15 alkyl amino group with a positive charge, or a glycoside.
摘要翻译：本发明提供新颖的化学修饰的突变丝氨酸水解酶，其催化转酰胺化和/或转肽化和/或酯交换反应。修饰的丝氨酸水解酶在被半胱氨酸替代的子位点中具有一个或多个氨基酸残基，其中通过用提供包含选自以下的部分的硫醇侧链的取代基取代半胱氨酸中的巯基氢来修饰半胱氨酸。极性芳族取代基，带正电荷的烷基氨基和糖苷。在特别优选的实施方案中，取代基包括恶唑烷酮，带正电荷的C1至C15烷基氨基或糖苷。

6. 发明申请

US20110262419A1 SPECIFICALLY TARGETED CATALYTIC ANTAGONISTS AND USES THEREOF 失效
标题翻译：特异性靶向催化拮抗剂及其用途
公开(公告)号：US20110262419A1
公开(公告)日：2011-10-27
申请号：US12953378
申请日：2010-11-23
申请人： Benjamin G. Davis , John Bryan Jones , Richard R. Bott , Karl John Stanford , David Aaron Estell
发明人： Benjamin G. Davis , John Bryan Jones , Richard R. Bott , Karl John Stanford , David Aaron Estell
IPC分类号： A61K38/48 , A61P29/00 , A61P37/00 , A61P31/12 , A61P31/04
CPC分类号： B82Y5/00 , A61K47/51 , A61K47/665 , A61K47/6898
摘要： This invention provides chimeric molecules that are catalytic antagonists of a target molecule. The catalytic antagonists of this invention preferably comprise a targeting moiety attached to an enzyme that degrades the molecule specifically bound by the targeting moiety. The catalytic antagonists of this invention thus bind to a target recognized by the targeting moiety (e.g., a receptor) the enzyme component of the chimera then degrades all or part of the target. This typically results in a reduction or loss of activity of the target and release of the chimeric molecule. The chimeric molecule is then free to attack and degrade another target molecule.
摘要翻译：本发明提供作为靶分子的催化拮抗剂的嵌合分子。本发明的催化拮抗剂优选包含与降解由靶向部分特异性结合的分子的酶连接的靶向部分。因此，本发明的催化拮抗剂与靶向部分识别的靶（例如受体）结合，嵌合体的酶组分然后降解靶的全部或部分。这通常导致靶的活性降低或丧失，并释放嵌合分子。然后嵌合分子可以自由地攻击和降解另一个靶分子。

7. 发明授权

US07371553B2 Chemically modified enzymes with multiple charged variants 有权
标题翻译：具有多种带电荷变体的化学修饰的酶
公开(公告)号：US07371553B2
公开(公告)日：2008-05-13
申请号：US10993827
申请日：2004-11-19
申请人： Benjamin G. Davis , John Bryan Jones , Richard R. Bott
发明人： Benjamin G. Davis , John Bryan Jones , Richard R. Bott
IPC分类号： C11D3/386 , C11D7/42 , C12N9/50 , C12N9/54 , C07H21/04
CPC分类号： C12N9/6408 , C12N9/50 , C12N9/54 , C12N2310/334
摘要： This invention provides modified enzymes comprising one or more amino acid residues replaced by cysteine residues, where the cysteine residues are modified by replacing the thiol hydrogen in the cysteine residues with a substituent group providing a thiol side chain comprising a multiply charged moiety. The enzymes show improved interaction and/or specificity and/or activity with charged substrates.
摘要翻译：本发明提供了包含被半胱氨酸残基取代的一个或多个氨基酸残基的修饰的酶，其中通过用提供包含多电荷部分的硫醇侧链的取代基代替半胱氨酸残基中的巯基氢来修饰半胱氨酸残基。酶与带电底物显示改善的相互作用和/或特异性和/或活性。

8. 发明授权

US06627744B2 Synthesis of glycodendrimer reagents 有权
标题翻译：糖苷配基试剂的合成
公开(公告)号：US06627744B2
公开(公告)日：2003-09-30
申请号：US09824827
申请日：2001-04-02
申请人： Benjamin G. Davis , John Bryan Jones , Richard R. Bott
发明人： Benjamin G. Davis , John Bryan Jones , Richard R. Bott
IPC分类号： C07H1700
CPC分类号： B82Y5/00 , A61K47/51 , A61K47/665 , A61K47/6898 , C07H5/10 , C07K14/36
摘要： The present invention relates to a chemically modified mutant protein including a cysteine residue substituted for a residue other than cysteine n a precursor protein, the substituted cysteine residue being subsequently modified by reacting the cysteine residue with a glycosylated thiosulfonate. Also a method of producing the chemically modified mutant protein is provided. The present invention also relates to a glycosylated methanethiosulfonate. Another aspect of the present invention is a method of modifying the functional characteristics of a protein including providing a protein and reacting the protein with a glycosylated methanethiosulfonate reagent under conditions effective to produce a glycoprotein with altered functional characteristics as compared to the protein. In addition, the present invention relates to methods of determining the structure-function relationships of chemically modified mutant proteins. The present invention also relates to synthetic methods for producing thio-glycoses, the thio-glycoses so produced, and to methods for producing glycodendrimer reagents.
摘要翻译：本发明涉及一种化学修饰的突变蛋白，其包含半胱氨酸残基，其取代了半胱氨酸以外的残基而不是前体蛋白，随后通过半胱氨酸残基与糖基化硫代磺酸酯反应来修饰取代的半胱氨酸残基。还提供了一种生产化学修饰的突变蛋白的方法。本发明还涉及糖基化甲磺酸盐。本发明的另一方面是一种改变蛋白质的功能特征的方法，包括提供蛋白质并使蛋白质与糖基化甲磺酸盐试剂在与蛋白质相比产生具有改变的功能特征的糖蛋白的条件下反应。此外，本发明涉及确定化学修饰的突变蛋白的结构 - 功能关系的方法。本发明还涉及用于制备硫代糖糖，如此制备的硫代糖糖的合成方法，以及制备糖苷配基体试剂的方法。

9. 发明授权

US08357524B2 Chemically modified mutant serine hydrolases show improved catalytic activity and chiral selectivity 失效
标题翻译：化学修饰的突变丝氨酸水解酶显示出改进的催化活性和手性选择性
公开(公告)号：US08357524B2
公开(公告)日：2013-01-22
申请号：US13561257
申请日：2012-07-30
申请人： John Bryan Jones , Michael Dickman , Richard C. Lloyd
发明人： John Bryan Jones , Michael Dickman , Richard C. Lloyd
IPC分类号： C12N9/52 , C12N9/56 , C07D417/00 , C12N15/57 , C12N15/74
CPC分类号： C12N9/54
摘要： This invention provides novel chemically modified mutant serine hydrolases that catalyze a transamidation and/or a transpeptidation and/or a transesterification reaction. The modified serine hydrolases have one or more amino acid residues in a subsite replaced with a cysteine, wherein the cysteine is modified by replacing the thiol hydrogen in the cysteine with a substituent group providing a thiol side chain comprising a moiety selected from the group consisting of a polar aromatic substituent, an alkyl amino group with a positive charge, and a glycoside. In particularly preferred embodiments, the substitutents include an oxazolidinone, a C1 to C15 alkyl amino group with a positive charge, or a glycoside.
摘要翻译：本发明提供新颖的化学修饰的突变丝氨酸水解酶，其催化转酰胺化和/或转肽化和/或酯交换反应。修饰的丝氨酸水解酶在被半胱氨酸替代的子位点中具有一个或多个氨基酸残基，其中通过用提供包含选自以下的部分的硫醇侧链的取代基取代半胱氨酸中的巯基氢来修饰半胱氨酸。极性芳族取代基，带正电荷的烷基氨基和糖苷。在特别优选的实施方案中，取代基包括恶唑烷酮，带正电荷的C1至C15烷基氨基或糖苷。

10. 发明申请

US20080193389A1 Use of glycodendrimer reagents for inhibiting adhesion by microorganisms 审中-公开
标题翻译：使用糖苷配基试剂抑制微生物的粘附
公开(公告)号：US20080193389A1
公开(公告)日：2008-08-14
申请号：US11584158
申请日：2006-10-20
申请人： Richard R. Bott , M. M. Cowan , Benjamin G. Davis , John Bryan Jones
发明人： Richard R. Bott , M. M. Cowan , Benjamin G. Davis , John Bryan Jones
IPC分类号： A61K8/66 , A61K38/48 , C12N5/06 , A01N47/08
CPC分类号： C07H5/10 , A61K38/43 , A61K38/48 , A61K38/482 , B82Y5/00 , C07K14/36
摘要： The present invention is directed to glyodendrimeric proteases, composition with glycodendrimeric proteases and methods for inhibiting adhesion binding in microorganisms by contacting microorganisms with a glycodendrimeric protease or a composition with a glycodendrimeric protease. The invention may be used to treat patients in need of treatment.
摘要翻译：本发明涉及甘油三聚蛋白酶，具有甘氨酸三聚体蛋白酶的组合物和通过使微生物与糖基配体蛋白酶或组合物与糖基配体蛋白酶接触来抑制微生物中粘附结合的方法。本发明可用于治疗需要治疗的患者。

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