📜乳清酸置于乙醇,铂体系中,80.0 °C,2.35 Mpa 条件下,反应生成2,6-二氧代六氢嘧啶-4-羧酸 参考文献:Chemistry Of The Dihydropyrimidines. Ultraviolet Spectra And Alkaline Decomposition1A 标题:Chemistry Of The Dihydropyrimidines. Ultraviolet Spectra And Alkaline Decomposition1A 摘要: Doi:10.1021/ja01643A018
专利号:US-10920229-B2 优先权日:2014-07-16 标 题:Method for improving heterologous synthesis of Escherichia coli into polyketides and use of same 发明人:WANG YONG; XIONG ZHIQIANG; SONG SHUJIE; LIU QIAOXIA; WANG JIANFENG 权利人:SHANGHAI INST BIOLOGICAL SCIENCES CAS; CAS CENTER FOR EXCELLENCE IN MOLECULAR PLANT SCIENCES 摘要:The present invention relates to a method for improving the heterologous synthesis of a polyketide by E. coli and use thereof. The yield of the polyketide heterologously synthesized by E. coli is significantly increased by attenuating the expression of seventy-two genes, such as sucC and talB, in a host strain, wherein the highest yield increase rate can reach 60% or more. Currently, erythromycin is the most clear model compound in the study on the biosynthesis of polyketids. The production strain of the present invention enables massive accumulation of 6-deoxyerythronolide (6-dEB), an erythromycin precursor, in the fermentation process, laying the foundation for the industrial production of the heterologous synthesis of erythromycin by E. coli.
专利号:US-7820795-B2 优先权日:2004-03-30 标 题:Lactobacillus fermentum N-desoxyribosyl transferases and the use thereof for enzymatic synthesis of 2′, 3′—didesoxynucleosides and 2′,3′- didehydro-2′,3′- didesoxynucleosides 发明人:KAMINSKI PIERRE-ALEXANDRE 权利人:PASTEUR INSTITUT 摘要:N-deoxyribosyl transferases of Lactobacillus fermentum and their analogues, as well their use for the enzymatic synthesis of 2′,3′-dideoxynucleosides and 2′,3′-didehydro-2′,3′-dideoxynucleosides. These transferases and their analogues include a N-deoxyribosyl transferase protein (DTP) that has at least 70%-95% identity with the polypeptide of SEQ ID NO: 2 or SEQ ID NO: 4, that retains residues Y13, D77, D97, E103, and M312 which respectively correspond to positions 13, 77, 97, 103, and 132 of SEQ ID NO: 2; and that has threonine at a position corresponding to position 15 of SEQ ID NO: 2 or SEQ ID NO: 4. Polynucleotides, vectors and host cells encoding these N-deoxyribosyl transferases and their analogues.
专利号:US-2004006137-A1 优先权日:2002-06-28 标题:Asymmetric synthesis of amino-pyrrolidinones and a crystalline, free-base amino-pyrrolidinone 发明人:WALTERMIRE ROBERT E; CAMPAGNA SILVIO; SAVAGE SCOTT A; BORDAWEKAR SHAILENDRA; MADUSKUIE THOMAS P; DESIKAN SRIDHAR; ANDERSON STEPHEN R 摘要:A novel process for the asymmetric synthesis of an amino-pyrrolidinone of the type shown below is described. n n n These compounds are useful as intermediates for MMP and TACE inhibitors. n Crystalline, free-base form of Compound J ((2R)-2-((3R)-3-amino-3-{-[(2-methyl-4-quinolinyl)methoxy]phenyl}-2-oxopyrrolidinyl)-N-hydroxy-4-methylpentanamide): n n n which is useful as a TACE inhibitor, pharmaceutical compositions comprising the same, and methods of using the same for treating inflammatory diseases are also described.
专利号:WO-2022226312-A1 优先权日:2021-04-22 标 题:Combination nucleotide pool depletion for treatment of viral infections and cancers 发明人:KUMAR VIKRAM; HESSON DAVID; DEMAREST JAMES 权利人:CLEAR CREEK BIO INC 摘要:The invention provides methods of treating cancers and viral infections by providing a combination of agents that inhibit both nucleotide synthesis and nucleotide salvage in the cells of a subject to prevent cancer proliferation and viral replication. The invention provides methods of depleting nucleotide pools by using both inhibitors of dihydroorotate dehydrogenase (DHODH), such as brequinar, which block synthesis of pyrimidine-based nucleotides, in combination of one or more nucleotide salvage inhibitors, for example deoxycytidine kinase (dCK) inhibitors, Equilibrative nucleoside transporter (ENT) inhibitors, and Uridine-cytidine kinase (UCK) inhibitors, which inhibit salvage of purine and/or pyrimidine-based nucleotides or nucleosides
专利号:US-9574189-B2 优先权日:2005-12-01 标题:Enzymatic encoding methods for efficient synthesis of large libraries 发明人:FRANCH THOMAS; LUNDORF MIKKEL DYBRO; JACOBSEN SØREN NYBOE; OLSEN EVA KAMPMANN; ANDERSEN ANNE LEE; HOLTMANN ANETTE; HANSEN ANDERS HOLM; SØRENSEN ANDERS MALLING; GOLDBECH ANNE; DE LEON DAEN; KALDOR DITTE KIEVSMOSE; SLØK FRANK ABILDGAARD; HUSEMOEN GITTE NYSTRUP; DOLBERG JOHANNES; Jensen Kim Birkebæ; PEDERSEN LENE; NØRREGAARD-MADSEN MADS; GODSKESEN MICHAEL ANDERS; GLAD SANNE SCHRØDER; NEVE SØREN; THISTED THOMAS; KRONBORG TINE TITILOLA AKINLEMINU; SAMS CHRISTIAN KLARNER; FELDING JAKOB; FRESKGÃ…RD PER-OLA; GOULIAEV ALEX HAAHR; PEDERSEN HENRIK 权利人:FRANCH THOMAS; LUNDORF MIKKEL DYBRO; JACOBSEN SØREN NYBOE; OLSEN EVA KAMPMANN; ANDERSEN ANNE LEE; HOLTMANN ANETTE; HANSEN ANDERS HOLM; SØRENSEN ANDERS MALLING; GOLDBECH ANNE; DE LEON DAEN; KALDOR DITTE KIEVSMOSE; SLØK FRANK ABILDGAARD; HUSEMOEN GITTE NYSTRUP; DOLBERG JOHANNES; Jensen Kim Birkebæ; PEDERSEN LENE; NØRREGAARD-MADSEN MADS; GODSKESEN MICHAEL ANDERS; GLAD SANNE SCHRØDER; NEVE SØREN; THISTED THOMAS; KRONBORG TINE TITILOLA AKINLEMINU; SAMS CHRISTIAN KLARNER; FELDING JAKOB; FRESKGÃ…RD PER-OLA; GOULIAEV ALEX HAAHR; PEDERSEN HENRIK; NUEVOLUTION AS 摘要:Disclosed is a method for obtaining a bifunctional complex comprising a molecule linked to a single stranded identifier oligonucleotide, wherein a nascent bifunctional complex comprising a chemical reaction site and a priming site for enzymatic addition of a tag is a) reacted at the chemical reaction site with one or more reactants, and b) reacted enzymatically at the priming site with one or more tag(s) identifying the reactant(s).
专利号:US-2022089775-A1 优先权日:2019-05-31 标题:Multiply auxotrophic cell line for the production of recombinant proteins and methods thereof 发明人:CHASIN LAWRENCE; ZHANG QINGHAO; DU ZHIMEI 权利人:UNIV COLUMBIA; MERCK SHARP & DOHME 摘要:The present invention provides, inter alia, a multiply auxotrophic cell line that is deficient in genes encoding enzymes that catalyze steps in the de novo synthesis of the pyrimidine and purine pathways, such as, e.g., uridine monophosphate synthetase (UMPS) and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (ATIC), respectively, for the production of recombinant proteins such as recombinant monoclonal and bispecific antibodies. Methods for preparing the multiply auxotrophic, in particular the doubly auxotrophic and octa-auxotrophic cell lines disclosed herein, methods for selecting a cell expressing a protein of interest, methods for producing a protein of interest, methods for optimizing the activity of a protein of interest, and kits for selecting a cell expressing a protein of interest, are also provided. In addition, recombinant proteins such as antibodies, including monoclonal and bispecific antibodies, made by the methods of the present disclosure are also provided.
1: Tiwari K, Kumar R, Dubey VK. Biochemical characterization of dihydroorotase of Leishmania donovani: Understanding pyrimidine metabolism through its inhibition. Biochimie. 2016 Dec;131:45-53. doi: 10.1016/j.biochi.2016.09.009. Epub 2016 Sep 17. doi: 10.1016/j.ymgme.2016.06.008. Epub 2016 Jun 14. doi: 10.1039/c5cp02016f. Epub 2015 Jun 19. doi: 10.1016/j.biochi.2014.01.001. Epub 2014 Jan 10. doi: 10.1039/c3cp52692e. doi: 10.1016/j.molbiopara.2013.05.008. Epub 2013 Jun 5. Available from http://www.ncbi.nlm.nih.gov/books/NBK115433/ Available from http://www.ncbi.nlm.nih.gov/books/NBK115431/ doi: 10.1093/hmg/dds218. Epub 2012 Jun 12. doi: 10.1016/j.molbiopara.2012.04.009. Epub 2012 May 8. 11: Couto SG, Cristina Nonato M, Costa-Filho AJ. Site directed spin labeling studies of Escherichia coli dihydroorotate dehydrogenase N-terminal extension. Biochem Biophys Res Commun. 2011 Oct 28;414(3):487-92. doi: 10.1016/j.bbrc.2011.09.092. Epub 2011 Oct 2. doi: 10.1021/bi200258y. Epub 2011 Mar 21. 13: Cheleski J, Wiggers HJ, Citadini AP, da Costa Filho AJ, Nonato MC, Montanari CA. Kinetic mechanism and catalysis of Trypanosoma cruzi dihydroorotate dehydrogenase enzyme evaluated by isothermal titration calorimetry. Anal Biochem. 2010 Apr 1;399(1):13-22. doi: 10.1016/j.ab.2009.11.018. Epub 2009 Nov 20. Review. Japanese. doi: 10.1021/bi900370s.
合成参考文献
参考文献:10.2174/092986710790820660 摘要:Rodrigues T, Lopes F, Moreira R. Inhibitors of the mitochondrial electron transport chain and de novo pyrimidine biosynthesis as antimalarials: The present status. Curr Med Chem. 2010;17(10):929–56. doi: 10.2174/092986710790820660. 参考文献:10.1093/ecam/neh139 摘要:Olalde Rangel JA, Magarici M, Amendola F, del Castillo O. The Systemic Theory of Living Systems. Part IV: Systemic Medicine—The Praxis. Evidence-Based Complementary and Alternative Medicine. 2005 Jan;2(4):429–39. doi: 10.1093/ecam/neh139. 参考文献:10.3389/fmicb.2011.00041 摘要:Ludwig M, Bryant DA. Transcription Profiling of the Model Cyanobacterium Synechococcus sp. Strain PCC 7002 by Next-Gen (SOLiD™) Sequencing of cDNA. Front Microbiol. 2011;2():41.