FI112116B - Menetelmä proteiinin 3-ulotteisen rakenneinformaation määrittämiseksi ja ravintoväliaine - Google Patents

Menetelmä proteiinin 3-ulotteisen rakenneinformaation määrittämiseksi ja ravintoväliaine Download PDF

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Publication number
FI112116B
FI112116B FI943745A FI943745A FI112116B FI 112116 B FI112116 B FI 112116B FI 943745 A FI943745 A FI 943745A FI 943745 A FI943745 A FI 943745A FI 112116 B FI112116 B FI 112116B
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protein
amino acids
nutrient medium
labeled
substituted
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FI943745A
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Finnish (fi)
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FI943745A0 (fi
FI943745A (fi
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Jonathan Miles Brown
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Martek Biosciences Corp
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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07BGENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B59/00Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
    • C07B59/001Acyclic or carbocyclic compounds
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/12Unicellular algae; Culture media therefor
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12PFERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P13/00Preparation of nitrogen-containing organic compounds
    • C12P13/04Alpha- or beta- amino acids
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/02Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
    • C12Q1/04Determining presence or kind of microorganism; Use of selective media for testing antibiotics or bacteriocides; Compositions containing a chemical indicator therefor
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/531Production of immunochemical test materials
    • G01N33/532Production of labelled immunochemicals
    • G01N33/534Production of labelled immunochemicals with radioactive label
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/58Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6803General methods of protein analysis not limited to specific proteins or families of proteins
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K2299/00Coordinates from 3D structures of peptides, e.g. proteins or enzymes
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02PCLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00Technologies relating to chemical industry
    • Y02P20/50Improvements relating to the production of bulk chemicals
    • Y02P20/55Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10TTECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00Chemistry: analytical and immunological testing
    • Y10T436/10Composition for standardization, calibration, simulation, stabilization, preparation or preservation; processes of use in preparation for chemical testing
    • Y10T436/105831Protein or peptide standard or control [e.g., hemoglobin, etc.]

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  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Organic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Microbiology (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Cell Biology (AREA)
  • Medicinal Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Pathology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Food Science & Technology (AREA)
  • General Physics & Mathematics (AREA)
  • General Engineering & Computer Science (AREA)
  • Biophysics (AREA)
  • Botany (AREA)
  • Bioinformatics & Computational Biology (AREA)
  • Toxicology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Virology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Peptides Or Proteins (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
FI943745A 1993-02-05 1994-08-15 Menetelmä proteiinin 3-ulotteisen rakenneinformaation määrittämiseksi ja ravintoväliaine FI112116B (fi)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US1424393 1993-02-05
US08/014,243 US5393669A (en) 1993-02-05 1993-02-05 Compositions and methods for protein structural determinations
US9401329 1994-02-07
PCT/US1994/001329 WO1994018339A1 (en) 1993-02-05 1994-02-07 Compositions and methods for protein structural determinations

Publications (3)

Publication Number Publication Date
FI943745A0 FI943745A0 (fi) 1994-08-15
FI943745A FI943745A (fi) 1994-08-15
FI112116B true FI112116B (fi) 2003-10-31

Family

ID=21764312

Family Applications (1)

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FI943745A FI112116B (fi) 1993-02-05 1994-08-15 Menetelmä proteiinin 3-ulotteisen rakenneinformaation määrittämiseksi ja ravintoväliaine

Country Status (13)

Country Link
US (3) US5393669A (ja)
EP (3) EP0636183B1 (ja)
JP (4) JPH07506192A (ja)
AT (1) ATE221918T1 (ja)
AU (2) AU678446B2 (ja)
CA (1) CA2129904A1 (ja)
DE (1) DE69431142T2 (ja)
DK (1) DK0636183T3 (ja)
ES (1) ES2181715T3 (ja)
FI (1) FI112116B (ja)
NO (1) NO943703L (ja)
PT (1) PT636183E (ja)
WO (1) WO1994018339A1 (ja)

Families Citing this family (45)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5393669A (en) * 1993-02-05 1995-02-28 Martek Biosciences Corp. Compositions and methods for protein structural determinations
US5891643A (en) * 1995-11-14 1999-04-06 Abbott Laboratories Use of nuclear magnetic resonance to design ligands to target biomolecules
US5989827A (en) * 1995-11-14 1999-11-23 Abbott Laboratories Use of nuclear magnetic resonance to design ligands to target biomolecules
ES2159056T5 (es) * 1995-11-14 2007-07-16 Abbott Laboratories Utilizacion de la resonancia magnetica nuclear para diseñar ligandos que se unen a biomoleculas blanco.
WO1997018321A1 (en) * 1995-11-15 1997-05-22 Martek Corporation Photosynthetic production of stable isotopically labeled recombinant proteins
US6168912B1 (en) 1996-01-23 2001-01-02 Martek Biosciences Corporation Method and kit for making a multidimensional combinatorial chemical library
US6111066A (en) * 1997-09-02 2000-08-29 Martek Biosciences Corporation Peptidic molecules which have been isotopically substituted with 13 C, 15 N and 2 H in the backbone but not in the sidechains
US20030220234A1 (en) * 1998-11-02 2003-11-27 Selvaraj Naicker Deuterated cyclosporine analogs and their use as immunodulating agents
JP2002534687A (ja) * 1998-12-30 2002-10-15 アメルシャム・パブリック・リミテッド・カンパニー 過分極を使用したnmr分光学アッセイ
AU5880800A (en) * 1999-06-25 2001-01-31 Battelle Memorial Institute Use of non-lossy solvents as a means to improve the high-field nmr sensitivity of biological samples
JP2003532900A (ja) * 2000-05-05 2003-11-05 パーデュー・リサーチ・ファウンデーション タンパク質を同定及び定量化するための親和性により選択されるサインペプチド
US6762041B2 (en) 2000-05-15 2004-07-13 Ajinomoto Co., Inc. Method for isotope labeling of protein with enzyme
US6882939B2 (en) * 2000-10-20 2005-04-19 Prospect Pharma Rapid determination of protein global folds
AU2002224440A1 (en) * 2000-10-20 2002-05-06 Martek Biosciences Corporation Rapid determination of protein global folds
US20030068651A1 (en) * 2001-03-12 2003-04-10 Cheryl Arrowsmith Multi-target analysis of gene families for chemistry of high affinity and selective small molecules and other therapeutics
US7256047B2 (en) * 2001-05-01 2007-08-14 Board Of Regents, The University Of Texas System Measurement of gluconeogenesis and intermediary metabolism using stable isotopes
WO2003006488A1 (en) * 2001-07-13 2003-01-23 The Regents Of The University Of California In-cell nmr spectroscopy
WO2003025156A2 (en) * 2001-09-18 2003-03-27 Affinium Pharmaceuticals, Inc. Methods and apparatuses for purification
US7449170B2 (en) * 2001-09-27 2008-11-11 Purdue Research Foundation Materials and methods for controlling isotope effects during fractionation of analytes
ES2326040T3 (es) * 2001-10-19 2009-09-29 Isotechnika Inc. Sintesis de analogos de ciclosporina.
CA2471105C (en) * 2001-12-19 2010-01-12 Japan Science And Technology Agency Stable isotope-labeled amino acid and method for incorporating the same into target protein, nmr method for the structural analysis of protein and method for producing regio-selective stable isotope-labeled fumaric acid and tartaric acid
US20040072356A1 (en) * 2002-02-20 2004-04-15 Guillermo Senisterra Methods and apparatuses for characterizing stability of biological molecules
US20050079526A1 (en) * 2002-02-20 2005-04-14 Affinium Pharmaceuticals, Inc. Methods and apparatuses for characterizing refolding and aggregation of biological molecules
US20050181464A1 (en) * 2002-04-04 2005-08-18 Affinium Pharmaceuticals, Inc. Novel purified polypeptides from bacteria
WO2003087834A2 (en) * 2002-04-08 2003-10-23 Affinium Pharmaceuticals, Inc. High throughput analysis of recombinant proteins in multi-well plates
NO20023357D0 (no) * 2002-04-19 2002-07-11 Amersham Health As Blanding
JP2005528915A (ja) * 2002-06-10 2005-09-29 プロスペクト ファーマ タンパク質およびタンパク質/リガンド複合体に関するダイナミックおよび構造データを得る方法
US20040121445A1 (en) * 2002-07-31 2004-06-24 Fabien Marino Cell cultures
CA2466792A1 (en) * 2003-05-16 2004-11-16 Affinium Pharmaceuticals, Inc. Evaluation of spectra
US20070082399A1 (en) * 2003-07-11 2007-04-12 Tatiana A Egorova-Zachernyuk Compositions and method for stable isotope labelling of biological compounds
EP1678198A4 (en) * 2003-10-07 2007-12-05 Prospect Pharma SIDE CHAIN DEUTERATED AMINO ACIDS AND METHOD OF USE
JP5019280B2 (ja) 2003-10-31 2012-09-05 独立行政法人科学技術振興機構 安定同位体標識芳香族アミノ酸、その標的蛋白質への組み込み方法並びに蛋白質のnmr構造解析方法
EP1899453B1 (en) 2005-06-07 2013-12-18 Ocean Nutrition Canada Limited Eukaryotic microorganisms for producing lipids and antioxidants
GB0604647D0 (en) 2006-03-08 2006-04-19 Shchepinov Mikhail Stabilized food supplements and their derivatives
WO2008004088A2 (en) * 2006-07-05 2008-01-10 Centre National De La Recherche Scientifique (C.N.R.S.) Iron-copper co-catalyzed process for carbon-carbon or carbon-heteroatom bonding
US9023616B2 (en) * 2006-08-01 2015-05-05 Dsm Nutritional Products Ag Oil producing microbes and method of modification thereof
DE102011007790A1 (de) * 2011-04-20 2012-10-25 Wacker Chemie Ag Verfahren zur Reinigung von L-Cystein
PT2970926T (pt) 2013-03-13 2018-03-22 Dsm Nutritional Products Ag Modificação genética de microrganismos
US20140260586A1 (en) * 2013-03-14 2014-09-18 Schlumberger Technology Corporation Method to perform rapid formation fluid analysis
JP2015067581A (ja) * 2013-09-30 2015-04-13 国立大学法人京都大学 多重共鳴用のプローブ
ES2959411T3 (es) * 2013-11-13 2024-02-26 Nanonord As Método para la determinación cuantitativa de nitrógeno en un fluido acuoso
CN104030942B (zh) * 2014-06-09 2016-08-24 浙江普洛医药科技有限公司 一种L-α-氨基丁酰胺盐酸盐的制备方法
EP3452078A4 (en) * 2016-05-02 2020-01-22 Retrotope, Inc. ISOTOPICALLY MODIFIED COMPOSITION AND THEIR THERAPEUTIC USE
CN107793209A (zh) * 2016-08-30 2018-03-13 泰生科技香港有限公司 稳定性同位素标记植物的专用培养基、其制备方法及用途
JOP20190097A1 (ar) 2016-10-27 2019-04-28 Janssen Pharmaceutica Nv الجلوبولينات المناعية واستخداماتها

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4182656A (en) * 1976-09-10 1980-01-08 Johnston Laboratories, Inc. Method for detecting the presence of biologically active agents utilizing 13 C-labeled substrates
US4281061A (en) * 1979-07-27 1981-07-28 Syva Company Double antibody for enhanced sensitivity in immunoassay
JPS5811857A (ja) * 1981-07-15 1983-01-22 Yamasa Shoyu Co Ltd アデノシンの定量法
CA2058930C (en) * 1989-06-14 2000-08-15 John C. Cox (Deceased) Media for cell growth and method for making them
JP2517688B2 (ja) * 1989-12-25 1996-07-24 日本電子株式会社 3次元核磁気共鳴スペクトルの対称化処理方法
JPH0446143A (ja) * 1990-06-11 1992-02-17 Hitachi Ltd 同位体多重標識アミノ酸の合成法
US5393669A (en) * 1993-02-05 1995-02-28 Martek Biosciences Corp. Compositions and methods for protein structural determinations
US5478729A (en) * 1994-04-28 1995-12-26 Syntex (U.S.A.) Inc. Immunoassay for homocysteine

Also Published As

Publication number Publication date
EP0636183A4 (en) 1997-01-22
EP1191033A3 (en) 2003-07-30
FI943745A0 (fi) 1994-08-15
DE69431142T2 (de) 2003-10-09
NO943703L (no) 1994-11-23
ES2181715T3 (es) 2003-03-01
US5817474A (en) 1998-10-06
AU3608797A (en) 1997-12-04
PT636183E (pt) 2002-11-29
JP2004115528A (ja) 2004-04-15
AU6236394A (en) 1994-08-29
EP1193271A3 (en) 2004-03-24
NO943703D0 (no) 1994-10-04
EP0636183B1 (en) 2002-08-07
JP2004125801A (ja) 2004-04-22
CA2129904A1 (en) 1994-08-18
DK0636183T3 (da) 2002-12-02
AU711468B2 (en) 1999-10-14
EP1193271A2 (en) 2002-04-03
US5627044A (en) 1997-05-06
ATE221918T1 (de) 2002-08-15
US5393669A (en) 1995-02-28
DE69431142D1 (de) 2002-09-12
WO1994018339A1 (en) 1994-08-18
EP0636183A1 (en) 1995-02-01
JP2004113248A (ja) 2004-04-15
FI943745A (fi) 1994-08-15
JPH07506192A (ja) 1995-07-06
EP1191033A2 (en) 2002-03-27
AU678446B2 (en) 1997-05-29

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