Application of Nanopore Sensors for Biomolecular Interactions and Drug Discovery

Jeong, Ki-Baek; Kim, Jinsik; Dhanasekar, Naresh Niranjan; Lee, Mi-Kyung; Chi, Seung‐Wook

doi:10.1002/asia.202200679

Cited by 6 publications

(6 citation statements)

References 153 publications

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“…Besides, inspiring selective biosensor and biomimetic material design or being a target for a novel drug, nanopores are regarded to have the potential for characterizing proteins and nucleic acids and be used for sequencing of DNA and proteins (Jeong et al 2022 ; Milenkovic et al 2023 ). The design of membranes harboring specific nanopores can even be used for energy generation.…”

Section: Biomimetic Desalination Membranesmentioning

confidence: 99%

Microbial membrane transport proteins and their biotechnological applications

Özkan,

Yılmaz,

Ergenekon

et al. 2024

World J Microbiol Biotechnol

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Because of the hydrophobic nature of the membrane lipid bilayer, the majority of the hydrophilic solutes require special transportation mechanisms for passing through the cell membrane. Integral membrane transport proteins (MTPs), which belong to the Major Intrinsic Protein Family, facilitate the transport of these solutes across cell membranes. MTPs including aquaporins and carrier proteins are transmembrane proteins spanning across the cell membrane. The easy handling of microorganisms enabled the discovery of a remarkable number of transport proteins specific to different substances. It has been realized that these transporters have very important roles in the survival of microorganisms, their pathogenesis, and antimicrobial resistance. Astonishing features related to the solute specificity of these proteins have led to the acceleration of the research on the discovery of their properties and the development of innovative products in which these unique properties are used or imitated. Studies on microbial MTPs range from the discovery and characterization of a novel transporter protein to the mining and screening of them in a large transporter library for particular functions, from simulations and modeling of specific transporters to the preparation of biomimetic synthetic materials for different purposes such as biosensors or filtration membranes. This review presents recent discoveries on microbial membrane transport proteins and focuses especially on formate nitrite transport proteins and aquaporins, and advances in their biotechnological applications.

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Section: Biomimetic Desalination Membranesmentioning

confidence: 99%

Microbial membrane transport proteins and their biotechnological applications

Özkan,

Yılmaz,

Ergenekon

et al. 2024

World J Microbiol Biotechnol

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“…As one of the classical biomolecular interactions, PNI is widely involved in the regulation of diverse life activities. 73 Gene replication, transcription, translation, modification, and other biological processes are inseparable from PNI. Aptamers are short synthetic DNA or RNA oligonucleotides which can bind to the target like proteins with specificity and high affinity.…”

Section: ■ Design Of Fp Tracers and Application Of Fp Assay In Ligand...mentioning

confidence: 99%

“…Protein–nucleic acid interaction (PNI) can be divided into protein–DNA interaction and protein–RNA interaction according to two types of biomolecules. As one of the classical biomolecular interactions, PNI is widely involved in the regulation of diverse life activities . Gene replication, transcription, translation, modification, and other biological processes are inseparable from PNI.…”

Section: Design Of Fp Tracers and Application Of Fp Assay In Ligand S...mentioning

confidence: 99%

Design of Tracers in Fluorescence Polarization Assay for Extensive Application in Small Molecule Drug Discovery

Hua

Wang

et al. 2023

J. Med. Chem.

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Development of fluorescence polarization (FP) assays, especially in a competitive manner, is a potent and mature tool for measuring the binding affinities of small molecules. This approach is suitable for high-throughput screening (HTS) for initial ligands and is also applicable for further study of the structure−activity relationships (SARs) of candidate compounds for drug discovery. Buffer and tracer, especially rational design of the tracer, play a vital role in an FP assay system. In this perspective, we provided different kinds of approaches for tracer design based on successful cases in recent years. We classified these tracers by different types of ligands in tracers, including peptide, nucleic acid, natural product, and small molecule. To make this technology accessible for more targets, we briefly described the basic theory and workflow, followed by highlighting the design and application of typical FP tracers from a perspective of medicinal chemistry. ■ SIGNIFICANCE• FP assays are potent tools for drug discovery. This perspective highlights the design of tracers, especially molecular selection, linker design, and fluorophore, and classifies tracers by ligand types. • We provide basic principles for developing FP assays and discuss their prospects for high-throughput screening and identification of small molecules as well as their structure−activity relationships. • This perspective elaborates the FP assay design process and its potential applications in small molecule drug discovery.

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“…Indeed, significant advances in polymer synthesis and their translation into nanopore functionalization had led to improved macromolecule identification, transport performance, and characterization through synthetic nanopores. − These smart nanopores hold promise for macromolecule identification, separation, and monitoring of conformational changes. Surface functionalization allows for specific control of molecular motion within the pore, thus enabling the detection and quantification of analytes based on specific ionic-conductance signatures. − Selectivity can be based on different interactions (size, charge, hydrophilic–hydrophobic interactions, specific recognition) and depends on key parameters, such as surface charge density, nanopore size and shape, conditions of the bulk solution in contact with the nanopore, wettability, or applied potentials. , …”

Section: Introductionmentioning

confidence: 99%

Orientational Pathways during Protein Translocation through Polymer-Modified Nanopores

Gonzalez Solveyra,

Perez Sirkin,

Tagliazucchi

et al. 2024

ACS Nano

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Protein translocation through nanopores holds significant promise for applications in biotechnology, biomolecular analysis, and medicine. However, the interpretation of signals generated by the translocation of the protein remains challenging. In this way, it is crucial to gain a comprehensive understanding on how macromolecules translocate through a nanopore and to identify what are the critical parameters that govern the process. In this study, we investigate the interplay between protein charge regulation, orientation, and nanopore surface modifications using a theoretical framework that allows us to explicitly take into account the acid−base reactions of the titrable amino acids in the proteins and in the polyelectrolytes grafted to the nanopore surface. Our goal is to thoroughly characterize the translocation process of different proteins (GFP, β-lactoglobulin, lysozyme, and RNase) through nanopores modified with weak polyacids. Our calculations show that the charge regulation mechanism exerts a profound effect on the translocation process. The pH-dependent interactions between proteins and charged polymers within the nanopore lead to diverse free energy landscapes with barriers, wells, and flat regions dictating translocation efficiency. Comparison of different proteins allows us to identify the significance of protein isoelectric point, size, and morphology in the translocation behavior. Taking advantage of these insights, we propose pHresponsive nanopores that can load proteins at one pH and release them at another, offering opportunities for controlled protein delivery, separation, and sensing applications.

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Application of Nanopore Sensors for Biomolecular Interactions and Drug Discovery

Cited by 6 publications

References 153 publications

Microbial membrane transport proteins and their biotechnological applications

Microbial membrane transport proteins and their biotechnological applications

Design of Tracers in Fluorescence Polarization Assay for Extensive Application in Small Molecule Drug Discovery

Orientational Pathways during Protein Translocation through Polymer-Modified Nanopores

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