Deuterium- and Tritium-Labelled Compounds: Applications in the Life Sciences

被引:598
作者
Atzrodt, Jens [1 ]
Derdau, Volker [1 ]
Kerr, William J. [2 ]
Reid, Marc [2 ]
机构
[1] Isotope Chem & Metabolite Synth, Integrated Drug Discovery, Med Chem, Ind Pk Hcchst, D-65926 Frankfurt, Germany
[2] Univ Strathclyde, WestCHEM, Dept Pure & Appl Chem, 295 Cathedral St, Glasgow G1 1XL, Lanark, Scotland
关键词
deuterium; drug discovery; isotopic labeling; life sciences; tritium; TANDEM MASS-SPECTROMETRY; HYDROGEN ISOTOPE FRACTIONATION; METABOLIC FLUX ANALYSIS; PLASMA-PROTEIN BINDING; LIQUID CHROMATOGRAPHY/MASS SPECTROMETRY; RATIO INFRARED-SPECTROSCOPY; IN-VITRO METABOLISM; MEASURING ENVIRONMENTAL PHENOLS; SCINTILLATION PROXIMITY ASSAY; MEMBRANE-TRANSPORT PROTEINS;
D O I
10.1002/anie.201704146
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Hydrogen isotopes are unique tools for identifying and understanding biological and chemical processes. Hydrogen isotope labelling allows for the traceless and direct incorporation of an additional mass or radioactive tag into an organic molecule with almost no changes in its chemical structure, physical properties, or biological activity. Using deuterium-labelled isotopologues to study the unique mass-spectrometric patterns generated from mixtures of biologically relevant molecules drastically simplifies analysis. Such methods are now providing unprecedented levels of insight in a wide and continuously growing range of applications in the life sciences and beyond. Tritium (H-3), in particular, has seen an increase in utilization, especially in pharmaceutical drug discovery. The efforts and costs associated with the synthesis of labelled compounds are more than compensated for by the enhanced molecular sensitivity during analysis and the high reliability of the data obtained. In this Review, advances in the application of hydrogen isotopes in the life sciences are described.
引用
收藏
页码:1758 / 1784
页数:27
相关论文
共 702 条
[1]   Validation of Heavy-Water Stable Isotope Probing for the Characterization of Rapidly Responding Soil Bacteria [J].
Aanderud, Zachary T. ;
Lennon, Jay T. .
APPLIED AND ENVIRONMENTAL MICROBIOLOGY, 2011, 77 (13) :4589-4596
[2]   Deuterated Water Effect in a Room Temperature Ionic Liquid: N,N-Diethyl-N-methyl-N-2-methoxyethyl Ammonium Tetrafluoroborate [J].
Abe, Hiroshi ;
Imai, Yusuke ;
Takekiyo, Takahiro ;
Yoshimura, Yukihiro .
JOURNAL OF PHYSICAL CHEMISTRY B, 2010, 114 (08) :2834-2839
[3]   Deuteration isotope effect on nonradiative transition of fac-tris (2-phenylpyridinato) iridium (III) complexes [J].
Abe, Taichi ;
Miyazawa, Akira ;
Konno, Hideo ;
Kawanishi, Yuji .
CHEMICAL PHYSICS LETTERS, 2010, 491 (4-6) :199-202
[4]   Mass spectrometry-based proteomics [J].
Aebersold, R ;
Mann, M .
NATURE, 2003, 422 (6928) :198-207
[5]   Towards dynamic metabolic flux analysis in CHO cell cultures [J].
Ahn, Woo Suk ;
Antoniewicz, Maciek R. .
BIOTECHNOLOGY JOURNAL, 2012, 7 (01) :61-74
[6]  
Akira K, 2001, DRUG METAB DISPOS, V29, P903
[7]   The Pharmacologic Basis for Antibody-Auristatin Conjugate Activity [J].
Alley, Stephen C. ;
Zhang, Xinqun ;
Okeley, Nicole M. ;
Anderson, Martha ;
Law, Che-Leung ;
Senter, Peter D. ;
Benjamin, Dennis R. .
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2009, 330 (03) :932-938
[8]   Next-generation proteomics: towards an integrative view of proteome dynamics [J].
Altelaar, A. F. Maarten ;
Munoz, Javier ;
Heck, Albert J. R. .
NATURE REVIEWS GENETICS, 2013, 14 (01) :35-48
[9]  
Ambroise Y, 2001, EUR J ORG CHEM, V2001, P3961
[10]  
Ankner John F, 2013, Curr Protoc Protein Sci, VChapter 17, DOI 10.1002/0471140864.ps1716s72