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Analitical techniques in combinatorial chemistry - Swarth M.E.

Swarth M.E. Analitical techniques in combinatorial chemistry - Marcel Dekker, 2000. - 311 p.
ISBN 0-8247-1939-5
Download (direct link): analyticaltechniquesincombinatorialchemistry2000.pdf
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65. KF Morris, CS Johnson Jr. Resolution of discrete and continuous molecular size distributions by means of diffusion-ordered 2D NMR spectroscopy. J Am Chem Soc 115:4291-4299, 1993.
66. KF Morris, P Stilbs, CS Johnson Jr. Analysis of mixtures based on molecular size and hydrophobicity by means of diffusion-ordered 2D NMR. Anal Chem 66:211-215, 1994.
67. M Lin, DA Jayawickrama, RA Rose, JA Delvisio, CK Larive. Nuclear magnetic resonance spectroscopy analysis of the selective complexation of the cis and trans isomers of phenylalanylproline by B-cyclodextrin. Anal Chim Acta 307: 449-457, 1995.
68. M Liu, JKNicholson, JC Lindon. High-resolution diffusion and relaxation edited one- and two-dimensional 1H NMR spectroscopy of biological fluids. Anal Chem 68 3370-3376, 1996.
69. N Birlirakis, E Guittet. A new approach in the use of gradients for size-resolved 2D-NMR experiments. J Am Chem Soc 118:13083-13084, 1996.
70. H Barjat, GA Morris, S Smart, AG Swanson, SC Williams. High-resolution diffusion-ordered 2D spectroscopy (HR-DOSY)—A new tool for the analysis of complex mixtures. J Magn Reson Series B 108:170-172, 1995.
71. M Shapiro, M Lin. Mixture analysis in combinatorial chemistry. Application of diffusion-resolved NMR spectroscopy. J Org Chem 61:7617-7619 1996.
72. CT Dooey, NN Chung, BC Wilkes, PW Schiller, JM Bidlack, GW Pasternak, RA Houghten. An all D-amino acid opioid peptide with central analgesic activity from a combinatorial library. Science 266:2019-2022, 1994.
73. K Burgess. Combinatorial technologies involving reiterative division/coupling/ recombinations: statistical considerations. J Med Chem 37:2985-2987, 1994.
74. E Erb, KD Janda, S Brenner. Recursive deconvolution of combinatorial chemical libraries. Proc Nat Acad Sci USA 91:11422-11426, 1994.
75. DJ Ecker, TA Vickers, R Hanecak, V Driver, K Anderson. Rational screening of oligonucleotide combinatorial libraries for drug discovery. Nucleic Acids Res 21:1853-1856, 1993.
76. R Fathi, MJ Rudolph, RG Gentles, R Patel, EW MacMillan, MS Reitman,
D Pelham, AF Cook. Synthesis and properties of combinatorial libraries of phos-phoramidates. J Org Chem 61:5600-5609, 1996.
77. S Borman, C&E N, 29-54, 1996.
78. RS Youngquist, GR Fuentes, MP Lacey, T Keough. Generation and screening
of combinatorial peptide libraries designed for rapid sequencing by mass spec-
trometry. J Am Chem Soc 117:3900-3906, 1995.
NMR Methods
79. X Cheng, R Chen, JE Bruce, BL Schwartz, GA Anderson, HSA Ofstadler, DC Gale, RD Smith, J Gao, GB Sigal, M Mammen, GM Whitesides. Using electrospray ionization FTICR mass spectrometry to study competitive binding of inhibitors to carbonic anhydrase. J Am Chem Soc 117:8859-8860, 1995.
80. Y-H Chu, YM Dunayevskiy, DP Kirby, P Vouros, BL Karger. Affinity capillary electrophoresis-mass spectrometry for screening combinatorial libraries. J Am Chem Soc 118:7827-7835, 1996.
81. M Lin, MJ Shapiro, JR Wareing. Diffusion-edited NMR—affinity NMR for direct observation of molecular interactions. J Am Chem Soc 119:5249-5250,
82. SB Shuker, PJ Hajduk, RP Meadows, SW Fesik. Discovering high-affinity ligands for proteins: SAR by NMR. Science 274:1531-1534, 1996.
The Role of Liquid Chromatography
Michael E. Swartz
Waters Corporation Milford, Massachusetts
Chromatography alone, or in combination with other analytical techniques, has been used for a number of years in the drug discovery process in support of traditional organic synthesis for compound identification, compound purity and stability determinations, from lead discovery to final lead optimization, testing, and candidate selection. However, in response to increasing demands in the pharmaceutical industry to accelerate the drug discovery process and identify lead compounds in increasing numbers, new avenues of approach, such as combinatorial chemistry, must be investigated.
Combinatorial chemistry synthesis techniques have presented new challenges to the analytical chemist. During lead discovery, libraries of large numbers of compounds, numbering from 10-20, to hundreds, thousands, ten of thousands, or even millions of compounds are generated. Therefore, due to the sheer numbers of compounds, assays must be rapid, as well as capable of determining quantity, purity, and whether or not the proper compound was synthesized. Further along the drug discovery path, during lead optimization and testing leading to candidate selection, compounds are required in larger quantities. Analytical techniques used in lead discovery now give way to preparative, mass-directed autopurification techniques, capable of isolating and purifying 10-20 mg of the compound of interest during a single chromatographic analysis. Furthermore, all of the assays, from the analytical to prepara-
tive scale, must be accessible to everyone in the drug discovery process, in what has become to be known as an ‘‘open access’’ environment. In response to these challenges, chromatographers have had to rethink their strategy in order to provide timely and complete information and feedback.
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