生醫感測科技於新藥開發的應用

Emerging Biosensor-Based Technology in the Field of Drug Discovery

張怡斌(Yi-Pin Chang) ； 曾明中(Ming-Chung Tseng) ； 朱延和(Yen-Ho Chu)

《科儀新知》 156期 (2007/02) Pp. 56-67

https://doi.org/10.29662/IT.200702.0006

摘要

現今的研究潮流，藥物開發是一股勢不可擋的趨勢，除了要能有效快速的進行活性篩選工作之外，也必須對篩選出之先導物有能力進行更進一步的深入分析，而生物感測正可以符合這些藥物開發的需求。在研發過程中，藥物與受體間的的動力及熱力學的研究可以清楚瞭解兩者的作用力、結構與活性關係，甚至引用在臨床上的測試。若能在早期先導藥物的研發進程中，預先以生物感測科技進行適切與深入的分析，不但可有效節省藥物開發所需的時間與成本，更能有助於先導藥物後續的最佳化。近年來依據光學原理的表面電漿共振與運用壓電效應的壓電石英微天秤，由於高靈敏度與可即時觀測等優點，正廣泛地被運用在各個生物分子作用力的探討上。本文中，筆者針對表面電漿共振與壓電石英微天秤在小分子藥物活性篩選、動力學及熱力學參數的求測來進行探討。

並列摘要

Biosensors, to date, have been not only employed in the early stages of drug discovery by screening potential targets and combinatorial libraries, but also moving down the pipeline and being used for significant quantitative measurements. From a drug development perspective, these thermodynamic and kinetic studies are essential for better understanding of receptor-ligand interactions, structure-activity relationships, and even preclinical tests which can beneficial for time and cost savings. During the last decade, surface plasmon resonance (SPR)-based optical biosensors are being used extensively for biomolecular interaction analysis, in addition, another emerging biosensing technology, quartz crystal microbalance (QCM) has also been introduced to achieve the aforementioned tasks. Despite recent advances of instrument sensitivity and data processing, working with small molecules and low affinity interactions remains a major challenge. As a result, we focus on applications of SPR and QCM biosensors for high-throughput screening and the acquisition of thermodynamic and kinetic parameters of different biding systems in this article.