Integrated and automated high-throughput purification of libraries on microscale

被引:9
|
作者
Ginsburg-Moraff, Carol [2 ]
Grob, Jonathan [2 ,4 ]
Chin, Karl [2 ]
Eastman, Grant [2 ]
Wildhaber, Sandra [1 ]
Bayliss, Mark [3 ]
Mues, Heinrich M. [1 ]
Palmieri, Marco [1 ]
Poirier, Jennifer
Reck, Marcel [1 ]
Luneau, Alexandre [1 ]
Rodde, Stephane [1 ]
Reilly, John [1 ]
Wagner, Trixie [1 ]
Brocklehurst, Cara E. [1 ]
Wyler, Rene [1 ]
Dunstan, David [2 ,5 ]
Marziale, Alexander N. [1 ,6 ]
机构
[1] Novartis Pharm AG, Novartis Inst Biomed Res, Global Discovery Chem, Fabrikstr 1, CH-4056 Basel, Switzerland
[2] Novartis Pharm AG, Novartis Inst Biomed Res, Global Discovery Chem, Cambridge, MA 02139 USA
[3] Virscidian Inc, Cary, NC 27511 USA
[4] Valo Hlth, 75 Hayden Ave, Lexington, MA 02421 USA
[5] Relay Therapeut, 399 Binney St, Cambridge, MA 02139 USA
[6] AstraZeneca, Pepparedsleden 1, S-43183 Molndal, Sweden
来源
SLAS TECHNOLOGY | 2022年 / 27卷 / 06期
关键词
High-throughput purification; Laboratory automation; Library purification; Microscale libraries; Analytical chemistry automation; PERFORMANCE LIQUID-CHROMATOGRAPHY; CHARGED AEROSOL DETECTION; UNIVERSAL DETECTORS; CHEMISTRY; GENERATION; INHIBITORS; PLATFORM; IDENTIFICATION; IMPURITIES; MODULATORS;
D O I
10.1016/j.slast.2022.08.002
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
We herein report the development of an automation platform for rapid purification and quantification of chem-ical libraries including reformatting of chemical matter to 10 mM DMSO stock solutions. This fully integrated workflow features tailored conditions for preparative reversed-phase (RP) HPLC-MS on microscale based on ana-lytical data, online fraction QC and CAD-based quantification as well as automated reformatting to enable rapid purification of chemical libraries. This automated workflow is entirely solution-based, eliminating the need to weigh or handle solids. This increases process efficiency and creates a link between high-throughput synthesis and profiling of novel chemical matter with respect to biological and physicochemical properties in relevant assays.
引用
收藏
页码:350 / 360
页数:11
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