Ultra-high-throughput SPE-MALDI workflow: Blueprint for efficient purification and screening of peptide libraries

被引：16

作者：

Bennett, Raffeal ^{[1
]}

Pirrone, Gregory F. ^{[1
]}

Nowak, Timothy ^{[1
]}

Mukherjee, Debopreeti ^{[1
]}

Shchurik, Vladimir ^{[1
]}

Mapelli, Claudio ^{[2
]}

Hickey, Jennifer L. ^{[2
]}

Regalado, Erik L. ^{[1
]}

Mangion, Ian ^{[1
]}

Makarov, Alexey A. ^{[1
]}

机构：

[1] Merck & Co Inc, MRL, Analyt Res & Dev, Rahway, NJ 07065 USA

[2] Merck & Co Inc, MRL, Chem Capabil Accelerating Therapeut, Discovery Chem, Kenilworth, NJ 07033 USA

来源：

ANALYTICA CHIMICA ACTA | 2021年 / 1142卷 / 1142期

关键词：

Solid-phase extraction; MALDI-MS; High-throughput screening; Peptide; Resin screening; High-throughput analysis; mRNA display; SCALE; DESIGN;

D O I：

10.1016/j.aca.2020.10.045

中图分类号：

O65 [分析化学];

学科分类号：

070302 ; 081704 ;

摘要：

At the forefront of synthetic endeavors in the pharmaceutical industry, including drug discovery and high-throughput screening, timelines are tight and large quantities of pure chemical targets are rarely available. In this regard, the development of novel and increasingly challenging chemistries requires a commensurate level of innovation to develop reliable analytical assays and purification workflows with rapid turnaround that enables accelerated pharmacological evaluation. A small-scale automation platform enabling high-throughput analysis and purification to streamline the selection of candidate leads would be a transformative advance. Herein, we introduce an automation-friendly solid-phase extraction-matrix-assisted laser desorption/ionization (SPE-MALDI) platform applied to the high-throughput purification and analysis of peptide libraries. This advance enabled us to purify peptides from microgram levels in less than a day with results comparable to traditional high-performance liquid chromatography-diode array detection-mass spectrometry (HPLC-DAD-MS). (C) 2020 Elsevier B.V. All rights reserved.

引用

页码：10 / 18

页数：9

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