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抗癌药物的傅里叶变换红外光谱特征。能否确定药物的作用模式?

FTIR spectral signature of anticancer drugs. Can drug mode of action be identified?

作者信息

Mignolet Alix, Derenne Allison, Smolina Margarita, Wood Bayden R, Goormaghtigh Erik

机构信息

Center for Structural Biology and Bioinformatics, Laboratory for the Structure and Function of Biological Membranes, Campus Plaine CP206/02, Université Libre de Bruxelles, CP206/2, B1050 Brussels, Belgium.

Centre for Biospectroscopy, School of Chemistry, Monash University, VIC 3800, Australia.

出版信息

Biochim Biophys Acta. 2016 Jan;1864(1):85-101. doi: 10.1016/j.bbapap.2015.08.010. Epub 2015 Aug 29.

Abstract

Infrared spectroscopy has brought invaluable information about proteins and about the mechanism of action of enzymes. These achievements are difficult to transpose to living organisms as all biological molecules absorb in the mid infrared, with usually a high degree of overlap. Deciphering the contribution of each enzyme is therefore almost impossible. On the other hand, small changes in the infrared spectra of cells induced by environmental conditions or drugs may provide an accurate signature of the metabolic shift experienced by the cell as a response to a change in the growth medium. The present paper aims at reviewing the contribution of infrared spectroscopy to the description of small chemical changes that occur in cells when they are exposed to a drug. In particular, this review will focus on cancer cells and anti-cancer drugs. Results accumulated so far tend to demonstrate that infrared spectroscopy could be a very accurate descriptor of the mode of action of anticancer drugs. If confirmed, such a segmentation of potential drugs according to their "mode of action" will be invaluable for the discovery of new therapeutic molecules. This article is part of a Special Issue entitled: Physiological Enzymology and Protein Functions.

摘要

红外光谱学为蛋白质及酶的作用机制带来了极为宝贵的信息。然而,由于所有生物分子在中红外波段均有吸收,且通常存在高度重叠,这些成果难以直接应用于活生物体。因此,几乎不可能解析每种酶的具体贡献。另一方面,环境条件或药物引起的细胞红外光谱的微小变化,可能为细胞因生长培养基变化而经历的代谢转变提供准确的特征标识。本文旨在综述红外光谱学在描述细胞暴露于药物时发生的微小化学变化方面的贡献。特别地,本综述将聚焦于癌细胞和抗癌药物。目前积累的结果倾向于表明,红外光谱学可能是抗癌药物作用模式的非常准确的描述手段。如果得到证实,根据潜在药物的“作用模式”进行这样的分类,对于发现新的治疗分子将具有极大价值。本文是名为“生理酶学与蛋白质功能”的特刊的一部分。

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