한빛사논문
- 조회1,614
Seon Joo Park†‡#, Heehong Yang‡#, Seung Hwan Lee‡, Hyun Seok Song§∥, Chul Soon Park†, Joonwon Bae⊥, Oh Seok Kwon*†, Tai Hyun Park*‡, and Jyongsik Jang*‡
† Harzards Monitoring Bionano Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 34141, Republic of Korea
‡ School of Chemical and Biological Engineering, Seoul National University, Seoul 08826, Republic of Korea
§ Division of Bioconvergence Analysis, Korea Basic Science Institute (KBSI), Daejeon 34133, Republic of Korea
∥ Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea
⊥ Department of Applied Chemistry, Dongduk Women’s University, Seoul 02748, Republic of Korea
*Corresponding Authors
Author Contributions
#S. J. Park and H. Yang contributed equally to this work.
Abstract
The field-effect transistor (FET) has been used in the development of diagnostic tools for several decades, leading to high-performance biosensors. Therefore, the FET platform can provide the foundation for the next generation of analytical methods. A major role of G-protein-coupled receptors (GPCRs) is in the transfer of external signals into the cell and promoting human body functions; thus, their principle application is in the screening of new drugs. The research community uses efficient systems to screen potential GPCR drugs; nevertheless, the need to develop GPCR-conjugated analytical devices remains for next-generation new drug screening. In this study, we proposed an approach for studying receptor agonism and antagonism by combining the roles of FETs and GPCRs in a dopamine receptor D1 (DRD1)-conjugated FET system, which is a suitable substitute for conventional cell-based receptor assays. DRD1 was reconstituted and purified to mimic native binding pockets that have highly discriminative interactions with DRD1 agonists/antagonists. The real-time responses from the DRD1-nanohybrid FET were highly sensitive and selective for dopamine agonists/antagonists, and their maximal response levels were clearly different depending on their DRD1 affinities. Moreover, the equilibrium constants (K) were estimated by fitting the response levels. Each K value indicates the variation in the affinity between DRD1 and the agonists/antagonists; a greater K value corresponds to a stronger DRD1 affinity in agonism, whereas a lower K value in antagonism indicates a stronger dopamine-blocking effect.
Keywords: agonism-antagonism; agonists-antagonists; dopamine; dopamine receptor D1; equilibrium constants; field-effect transistor; nanohybrids
논문정보
- Research article
- 2017년 05월 (BRIC 등록일 2017-06-15)
- 국내 연구진
- 바이오·의료융합 > 바이오센싱 및 나노바이오물질
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