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G-protein-coupled receptors function as logic gates for nanoparticle binding using systems and synthetic biology approach

Published online by Cambridge University Press:  20 February 2019

Aman Chandra Kaushik
Affiliation:
State Key Laboratory of Microbial Metabolism and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China
Xueying Mao
Affiliation:
Qianweichang College, Shanghai University, Shanghai 200444, China
Cheng-Dong Li
Affiliation:
State Key Laboratory of Microbial Metabolism and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China
Yan Li
Affiliation:
College of Computer Science and Information Technology, Henan Normal University, Xixiang 453007, China
Dong-Qing Wei*
Affiliation:
State Key Laboratory of Microbial Metabolism and School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China
Shakti Sahi*
Affiliation:
School of Biotechnology, Gautam Buddha University, Greater Noida 201312, India
*
a)Address all correspondence to these authors. e-mail: dqwei@sjtu.edu.cn
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Abstract

G-protein-coupled receptor 142 (GPR142) belongs to rhodopsin family. GPR142 and GPR119, both Gq-coupled receptors, are expressed in pancreatic β cells of pancreas; their activation eventually leads to triggering of insulin secretion. In this paper, through a systems and synthetic biology approach, the effect of a common hit compound has been investigated in GPR142 and GPR119 pathways. This hit that has the potential to be developed as a lead for nanodrug was obtained through high-throughput virtual screening. The hit compound was further docked with nanoparticles (GOLD, SPION, and CeO2). The probable effect of this potential hit on insulin secretion in type 2 diabetes and its dynamic behavior was explored. Kinetic simulation was performed for cross-validation of its role in both the pathways. This study opens up a probable avenue in therapy of type 2 diabetes through regulation of GPR142 and GPR119 receptors. The biological circuit constructed may further have an application as a modulator to control the up- and downregulation of the biochemical pathway and can be implemented as sensors or nanochips for therapy.

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Copyright © Materials Research Society 2019 

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