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

页码：350 / 360

页数：11

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