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The multifaceted roles of mass spectrometric analysis in nucleic acids drug discovery and development
Mass Spectrometry Reviews ( IF 6.9 ) Pub Date : 2021-12-23 , DOI: 10.1002/mas.21766
Thomas Kenderdine 1 , Dan Fabris 1
Affiliation  

The deceptively simple concepts of mass determination and fragment analysis are the basis for the application of mass spectrometry (MS) to a boundless range of analytes, including fundamental components and polymeric forms of nucleic acids (NAs). This platform affords the intrinsic ability to observe first-hand the effects of NA-active drugs on the chemical structure, composition, and conformation of their targets, which might affect their ability to interact with cognate NAs, proteins, and other biomolecules present in a natural environment. The possibility of interfacing with high-performance separation techniques represents a multiplying factor that extends these capabilities to cover complex sample mixtures obtained from organisms that were exposed to NA-active drugs. This report provides a brief overview of these capabilities in the context of the analysis of the products of NA-drug activity and NA therapeutics. The selected examples offer proof-of-principle of the applicability of this platform to all phases of the journey undertaken by any successful NA drug from laboratory to bedside, and provide the rationale for its rapid expansion outside traditional laboratory settings in support to ever growing manufacturing operations.

中文翻译:

质谱分析在核酸药物发现和开发中的多方面作用

质量测定和片段分析看似简单的概念是将质谱 (MS) 应用于无限范围分析物的基础,包括核酸 (NA) 的基本成分和聚合形式。该平台提供了直接观察 NA 活性药物对其靶标的化学结构、组成和构象的影响的内在能力,这可能会影响它们与同源 NA、蛋白质和其他生物分子相互作用的能力自然环境。与高性能分离技术接口的可能性代表了一个倍增因素,将这些能力扩展到涵盖从暴露于 NA 活性药物的生物体中获得的复杂样品混合物。本报告在分析 NA 药物活性和 NA 治疗产品的背景下简要概述了这些功能。所选示例提供了该平台适用于任何成功的 NA 药物从实验室到床边的旅程的所有阶段的原理证明,并为其在传统实验室环境之外快速扩展以支持不断增长的制造业提供了理由操作。
更新日期:2021-12-23
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