title: Protein Activity Regulation: Inhibition by Closed-Loop Aptamer-Based Structures and Restoration by Near-IR Stimulation.
abstract: Regulation of protein activity is vital for understanding the molecular mechanism of biological activities. In this work, protein activity is suppressed by proximity-dependent surface hybridization and subsequently restored by near-infrared (NIR) light stimulation. Specifically, by constructing closed-loop structures with two aptamer-based affinity ligands, significantly enhanced inhibition of thrombin activity is achieved compared to traditional single affinity ligand based inhibitors. Furthermore, the activity of inhibited thrombin is efficiently recovered under NIR light stimulation by using gold nanorods (AuNRs) as photothermal agents to disrupt the closed-loop structures. Real-time and in situ monitoring of the conversion of fibrinogen into fibrin catalyzed by both inhibited and recovered thrombin was performed with light scattering spectroscopy and laser scanning confocal microscopy (LSCM). Thrombin trapped in the closed-loop structures shows slow reaction kinetics, while the photothermally liberated thrombin displays largely recovered catalytic activity. Human plasma was further employed to demonstrate that both the inhibited and restored thrombin can be applied to clotting reaction in reality. This strategy provides protein activity regulation for studying the molecular basis of biological activities and can be further applied to potential areas such as metabolic pathway regulation and the development of protein-inhibitor pharmaceuticals.
authors.affiliation: Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University , Wuhan 430072, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University , Wuhan 430072, China.|Ministry of Education, Key Laboratory for the Synthesis and Application of Organic Functional Molecules & College of Chemistry and Chemical Engineering, Hubei University , Wuhan 430062, China.
authors.forename: Yurong
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University , Wuhan 430072, China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Hu
authors.affiliation: Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University , Wuhan 430072, China.
authors.forename: Yu-Yan
authors.initials: YY
authors.lastname: Fang
authors.affiliation: Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University , Wuhan 430072, China.
authors.forename: Xinyang
authors.initials: X
authors.lastname: Li
authors.affiliation: Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University , Wuhan 430072, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.affiliation: Ministry of Education, Key Laboratory for the Synthesis and Application of Organic Functional Molecules & College of Chemistry and Chemical Engineering, Hubei University , Wuhan 430062, China.
authors.forename: Shengfu
authors.initials: S
authors.lastname: Wang
authors.affiliation: Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University , Wuhan 430072, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Yuan
mesh_terms: D052157:Aptamers, Nucleotide / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D006046:Gold / Q000737:chemistry; D006801:Humans; D007259:Infrared Rays; D008024:Ligands; D008958:Models, Molecular; D043942:Nanotubes / Q000737:chemistry; D009693:Nucleic Acid Hybridization; D011487:Protein Conformation; D020349:Surface Plasmon Resonance; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*
chemical_list: D052157:Aptamers, Nucleotide; D008024:Ligands; D006046:Gold; D013917:Thrombin