专利号:US-6451543-B1 优先权日:1998-08-31 标题:Lipid matrix-assisted chemical ligation and synthesis of membrane polypeptides 发明人:KOCHENDOERFER GERD G; HUNTER CHRISTIE L; KENT STEPHEN B H; BOTTI PAOLO 权利人:GRYPHON SCIENCES 摘要:The present invention relates to methods and compositions for lipid matrix-assisted chemical ligation and synthesis of membrane polypeptides that are incorporated in a lipid matrix. The invention is exemplified in production of a prefolded membrane polypeptide embedded within a lipid matrix via stepwise chemoselective chemical ligation of unprotected peptide segments, where at least one peptide segment is embedded in a lipid matrix. Any chemoselective reaction chemistry amenable for ligation of unprotected peptide segments can be employed. Suitable lipid matrices include liposomes, micelles, cell membrane patches and optically isotropic cubic lipidic phase matrices. Prefolded synthetic and semi-synthetic membrane polypeptides synthesized according to the methods and compositions of the invention also permit site-specific incorporation of one or more detectable moieties, such as a chromophore, which can be conveniently introduced during synthesis. The methods and compositions of the invention have multiple uses. For example, they can be used to assay ligand binding to membrane polypeptides and domains comprising a receptor, and thus are extremely useful for structure/function studies, drug screening/selection/design, and diagnostics and the like, including high-throughput applications. The methods and compositions of the invention are particularly suited for FRET analyses of previously inaccessible membrane polypeptides.
专利号:US-6528275-B1 优先权日:1996-04-24 标题:Substrates and inhibitors of proteolytic enzymes 发明人:QUIBELL MARTIN; JOHNSON TONY; HART TERANCE 权利人:MEDIVIR UK LTD 摘要:The present invention relates to the field of compounds which are substrates or inhibitors of proteolytic enzymes and to apparatus and methods for identifying substrates or inhibitors for proteolytic enzymes. We have devised a combinatorial method for the rapid indentification of binding motifs which will greatly expedite the synthesis of inhibitors of a variety of proteolytic enzymes such as aspartyl proteases, serine proteases, metallo proteases and cysteinyl proteases.
专利号:US-9470680-B2 优先权日:2011-02-28 标 题:Fluorescence-based approach to monitor release factor-catalyzed termination of protein synthesis 发明人:GONZALEZ JR RUBEN L; STERNBERG SAMUEL H; PULUKKUNAT DILEEP K 权利人:GONZALEZ JR RUBEN L; STERNBERG SAMUEL H; PULUKKUNAT DILEEP K; UNIV COLUMBIA 摘要:Provided are probes comprising a class 1 release factor conjugated to a fluorescent label and methods of making the probes. Also provided are methods for detecting conformational changes in ribosomes and associated molecules, such as class 1 release factors. In addition, methods of identifying a compound for reducing nonsense-mediated decay of mRNA and/or for inhibiting termination of protein synthesis at a premature stop codon, are described. Methods of assaying RF3 activity are also included.
专利号:US-7482425-B2 优先权日:1999-08-26 标题:Compositions for lipid matrix-assisted chemical ligation 发明人:KOCHENDOERFER GERD G; HUNTER CHRISTIE L; KENT STEPHEN B H; BOTTI PAOLO 权利人:AMYLIN PHARMACEUTICALS INC 摘要:The present invention relates to methods and compositions for lipid matrix-assisted chemical ligation and synthesis of membrane polypeptides that are incorporated in a lipid matrix. The invention is exemplified in production of a prefolded membrane polypeptide embedded within a lipid matrix via stepwise chemoselective chemical ligation of unprotected peptide segments, where at least one peptide segment is embedded in a lipid matrix. Any chemoselective reaction chemistry amenable for ligation of unprotected peptide segments can be employed. Suitable lipid matrices include liposomes, micelles, cell membrane patches and optically isotropic cubic lipidic phase matrices. Prefolded synthetic and semi-synthetic membrane polypeptides synthesized according to the methods and compositions of the invention also permit site-specific incorporation of one or more detectable moieties, such as a chromophore, which can be conveniently introduced during synthesis. The methods and compositions of the invention have multiple uses. For example, they can be used to assay ligand binding to membrane polypeptides and domains comprising a receptor, and thus are extremely useful for structure/function studies, drug screening/selection/design, and diagnostics and the like, including high-throughput applications. The methods and compositions of the invention are particularly suited for FRET analyses of previously inaccessible membrane polypeptides.
专利号:US-2003018169-A1 优先权日:1999-08-26 标 题:Lipid matrix-assisted chemical ligation and synthesis of membrane polypeptides
专利号:EP-1107979-A2 优先权日:1998-08-31 标题:Lipid matrix-assisted chemical ligation and synthesis of membrane polypeptides
参考文献:10.1016/j.bbrc.2023.08.050 摘要:Ikeda Y, Davis MI, Sumita K, Zheng Y, Kofuji S, Sasaki M, Hirota Y, Pragani R, Shen M, Boxer MB, Takeuchi K, Senda T, Simeonov A, Sasaki AT. Multimodal action of KRP203 on phosphoinositide kinases in vitro and in cells. Biochemical and Biophysical Research Communications. 2023 Oct;679():116–21. doi: 10.1016/j.bbrc.2023.08.050.