Biology & Life Sciences

Editor’s Picks: Chemical Tools & Probes

Updated June 20, 2017 Curated Collections

Small molecules that allow us to observe and manipulate biological systems by targeting and binding to specific targets are powerful tools in the field of Chemical Biology. These probes can inhibit a protein’s function, interact with nucleic acids, disrupt cellular processes and pathways, as well as allow researchers to study how a biological target functions within a given system.

In this Curated Collection, PLOS ONE presents some of the latest research on the development and uses of chemical probes, including in vivo and in vitro imaging, drug discovery, protein functions and cellular processes.

Image Credit: http://dx.doi.org/10.1371/journal.pone.0160522.g003

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Research Articles

Research Articles

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10.1371/journal.pone.0247376 CC BY 4.0

PLOS ONE Visualization of endogenous gut bacteria in Drosophila melanogaster using fluorescence in situ hybridization
February 19, 2021 Irfan Akhtar, Fiona A. Stewart, Anna Härle, Andrea Droste, Mathias Beller

All metazoans are colonized by a complex and diverse set of microorganisms. The microbes colonize all parts of the body and are especially…
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10.1371/journal.pone.0230057 CC BY 4.0

PLOS ONE NOTIFy (non-toxic lyophilized field)-FISH for the identification of biological agents by Fluorescence in situ Hybridization
March 6, 2020 Karin Aistleitner, Tina Sieper, Inga Stürz, Rimma Jeske, Susanne Tritscheller, Sonja Mantel, Alina Tscherne, Sabine Zange, Kilian Stoecker, Roman Wölfel

The rapid and reliable diagnostics of highly pathogenic bacteria under restricted field conditions poses one of the major challenges to…
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10.1371/journal.pone.0239145 CC BY 4.0

PLOS ONE Dual DNA binding mode of a turn-on red fluorescent probe thiazole coumarin
September 17, 2020 Sudakshina Ganguly, Debasis Ghosh, Nagarjun Narayanaswamy, T. Govindaraju, Gautam Basu

Turn-on fluorescent probes show enhanced emission upon DNA binding, advocating their importance in imaging cellular DNA. We have probed…
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10.1371/journal.pone.0243747 CC BY 4.0

PLOS ONE 5,5-Dialkylluciferins are thermal stable substrates for bioluminescence-based detection systems
December 14, 2020 Ce Shi, Michael P. Killoran, Mary P. Hall, Paul Otto, Monika G. Wood, Ethan Strauss, Lance P. Encell, Thomas Machleidt, Keith V. Wood, Thomas A. Kirkland

Firefly luciferase-based ATP detection assays are frequently used as a sensitive, cost-efficient method for monitoring hygiene in many…
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10.1371/journal.pone.0218897 CC BY 4.0

PLOS ONE Quantitative high-throughput screening assays for the discovery and development of SIRPα-CD47 interaction inhibitors
July 5, 2019 Thomas W. Miller, Joshua D. Amason, Elsa D. Garcin, Laurence Lamy, Patricia K. Dranchak, Ryan Macarthur, John Braisted, Jeffrey S. Rubin, Teresa L. Burgess, Catherine L. Farrell, David D. Roberts, James Inglese

CD47 is an immune checkpoint molecule that downregulates key aspects of both the innate and adaptive anti-tumor immune response via its…
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10.1371/journal.pone.0210305 CC BY 4.0

PLOS ONE Identifying small molecule probes of ENTPD5 through high throughput screening
June 26, 2019 Matthew A. Durst, Kiira Ratia, Arnon Lavie

Ectonucleoside Triphosphate Diphosphohydrolase 5 (ENTPD5) has been shown to be important in maintaining cellular function in cancer, and…
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10.1371/journal.pone.0211165 CC BY 4.0

PLOS ONE Targeted fluorescence lifetime probes reveal responsive organelle viscosity and membrane fluidity
February 14, 2019 Ida Emilie Steinmark, Arjuna L. James, Pei-Hua Chung, Penny E. Morton, Maddy Parsons, Cécile A. Dreiss, Christian D. Lorenz, Gokhan Yahioglu, Klaus Suhling

The only way to visually observe cellular viscosity, which can greatly influence biological reactions and has been linked to several human…
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10.1371/journal.pone.0211505 CC BY 4.0

PLOS ONE In-stem molecular beacon targeted to a 5′-region of tRNA inclusive of the D arm that detects mature tRNA with high sensitivity
January 29, 2019 Yuichi Miyoshi, Takashi Ohtsuki, Hiromu Kashida, Hiroyuki Asanuma, Kazunori Watanabe

Cellular functions are regulated by the up- and down-regulation and localization of RNA molecules. Therefore, many RNA detection methods…
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10.1371/journal.pone.0209195 CC BY 4.0

PLOS ONE Nab3’s localization to a nuclear granule in response to nutrient deprivation is determined by its essential prion-like domain
December 17, 2018 Travis J. Loya, Thomas W. O’Rourke, William C. Simke, Joshua B. Kelley, Daniel Reines

Ribonucleoprotein (RNP) granules are higher order assemblies of RNA, RNA-binding proteins, and other proteins, that regulate the…
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10.1371/journal.pone.0200006 CC BY 4.0

PLOS ONE Structure-activity study of furyl aryloxazole fluorescent probes for the detection of singlet oxygen
July 2, 2018 Renzo P. Zanocco, Roger Bresoli-Obach, Santi Nonell, Else Lemp, Antonio L. Zanocco

In this study, we report the synthesis and the photochemical behavior of a series of new "click-on" fluorescent probes designed to detect…
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10.1371/journal.pone.0197372 CC BY 4.0

PLOS ONE Small molecule inhibitors and CRISPR/Cas9 mutagenesis demonstrate that SMYD2 and SMYD3 activity are dispensable for autonomous cancer cell proliferation
June 1, 2018 Michael J. Thomenius, Jennifer Totman, Darren Harvey, Lorna H. Mitchell, Thomas V. Riera, Kat Cosmopoulos, Alexandra R. Grassian, Christine Klaus, Megan Foley, Elizabeth A. Admirand, Haris Jahic, Christina Majer, Tim Wigle, Suzanne L. Jacques, Jodi Gureasko, Dorothy Brach, Trupti Lingaraj, Kip West, Sherri Smith, Nathalie Rioux, Nigel J. Waters, Cuyue Tang, Alejandra Raimondi, Michael Munchhof, James E. Mills, Scott Ribich, Margaret Porter Scott, Kevin W. Kuntz, William P. Janzen, Mikel Moyer, Jesse J. Smith, Richard Chesworth, Robert A. Copeland, P. Ann Boriack-Sjodin

A key challenge in the development of precision medicine is defining the phenotypic consequences of pharmacological modulation of specific…
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10.1371/journal.pone.0197241 CC BY 4.0

PLOS ONE A gratuitous β-Lactamase inducer uncovers hidden active site dynamics of the Staphylococcus aureus BlaR1 sensor domain
May 17, 2018 Thomas E. Frederick, Jeffrey W. Peng

Increasing evidence shows that active sites of proteins have non-trivial conformational dynamics. These dynamics include active site…
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10.1371/journal.pone.0186548 CC BY 4.0

PLOS ONE Microencapsulated fluorescent pH probe as implantable sensor for monitoring the physiological state of fish embryos
October 18, 2017 Anton Gurkov, Anton Sadovoy, Ekaterina Shchapova, Cathleen Teh, Igor Meglinski, Maxim Timofeyev

In vivo physiological measurement is a major challenge in modern science and technology, as is environment conservation at the global…
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10.1371/journal.pone.0184627 CC BY 4.0

PLOS ONE Structure-based design, synthesis and crystallization of 2-arylquinazolines as lipid pocket ligands of p38α MAPK
September 11, 2017 Mike Bührmann, Bianca M. Wiedemann, Matthias P. Müller, Julia Hardick, Maria Ecke, Daniel Rauh

In protein kinase research, identifying and addressing small molecule binding sites other than the highly conserved ATP-pocket are of…
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10.1371/journal.pone.0179669 CC BY 4.0

PLOS ONE Polymerase-free measurement of microRNA-122 with single base specificity using single molecule arrays: Detection of drug-induced liver injury
July 5, 2017 David M. Rissin, Barbara López-Longarela, Salvatore Pernagallo, Hugh Ilyine, A. D. Bastiaan Vliegenthart, James W. Dear, Juan J. Díaz-Mochón, David C. Duffy

We have developed a single probe method for detecting microRNA from human serum using single molecule arrays, with sequence specificity…
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10.1371/journal.pone.0170618 CC BY 4.0

PLOS ONE Brachypodium distachyon – A Useful Model in the Qualification of Mutagen-Induced Micronuclei Using Multicolor FISH
January 24, 2017 Arita Kus, Jolanta Kwasniewska, Robert Hasterok

Brachypodium distachyon (Brachypodium) is now intensively utilized as a model grass species in various biological studies. Its favorable…
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10.1371/journal.pone.0011985

PLOS ONE Use of Activity-Based Probes to Develop High Throughput Screening Assays That Can Be Performed in Complex Cell Extracts
August 5, 2010 Edgar Deu, Zhimou Yang, Flora Wang, Michael Klemba, Matthew Bogyo
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10.1371/journal.pone.0131716

PLOS ONE The Histone Methyltransferase Inhibitor A-366 Uncovers a Role for G9a/GLP in the Epigenetics of Leukemia
July 6, 2015 William N. Pappano, Jun Guo, Yupeng He, Debra Ferguson, Sujatha Jagadeeswaran, Donald J. Osterling, Wenqing Gao, Julie K. Spence, Marina Pliushchev, Ramzi F. Sweis, Fritz G. Buchanan, Michael R. Michaelides, Alexander R. Shoemaker, Chris Tse, Gary G. Chiang
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10.1371/journal.pone.0132818

PLOS ONE Design of a Selective Substrate and Activity Based Probe for Human Neutrophil Serine Protease 4
July 14, 2015 Paulina Kasperkiewicz, Marcin Poreba, Scott J. Snipas, S. Jack Lin, Daniel Kirchhofer, Guy S. Salvesen, Marcin Drag
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10.1371/journal.pone.0134317

PLOS ONE A Pan-GTPase Inhibitor as a Molecular Probe
August 6, 2015 Lin Hong, Yuna Guo, Soumik BasuRay, Jacob O. Agola, Elsa Romero, Denise S. Simpson, Chad E. Schroeder, Peter Simons, Anna Waller, Matthew Garcia, Mark Carter, Oleg Ursu, Kristine Gouveia, Jennifer E. Golden, Jeffrey Aubé, Angela Wandinger-Ness, Larry A. Sklar
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10.1371/journal.pone.0115644

PLOS ONE Synthesis and Evaluation of a Novel Adenosine-Ribose Probe for Global-Scale Profiling of Nucleoside and Nucleotide-Binding Proteins
February 11, 2015 Shikha Mahajan, Roman Manetsch, David J. Merkler, Stanley M. Stevens Jr.
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10.1371/journal.pone.0149845

PLOS ONE Molecular Probing of the HPV-16 E6 Protein Alpha Helix Binding Groove with Small Molecule Inhibitors
February 25, 2016 Anne Rietz, Dino P. Petrov, Matthew Bartolowits, Marsha DeSmet, V. Jo Davisson, Elliot J. Androphy
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10.1371/journal.pone.0157146

PLOS ONE Discovery of Small-Molecule Modulators of the Human Y₄ Receptor
June 13, 2016 Gregory Sliwoski, Mario Schubert, Jan Stichel, David Weaver, Annette G. Beck-Sickinger, Jens Meiler
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10.1371/journal.pone.0161557

PLOS ONE A Molecular Probe for the Detection of Polar Lipids in Live Cells
August 23, 2016 Christie A. Bader, Tetyana Shandala, Elizabeth A. Carter, Angela Ivask, Taryn Guinan, Shane M. Hickey, Melissa V. Werrett, Phillip J. Wright, Peter V. Simpson, Stefano Stagni, Nicolas H. Voelcker, Peter A. Lay, Massimiliano Massi, Sally E. Plush, Douglas A. Brooks
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10.1371/journal.pone.0131037

PLOS ONE Development of a Bioluminescent Nitroreductase Probe for Preclinical Imaging
June 25, 2015 Anzhelika G. Vorobyeva, Michael Stanton, Aurélien Godinat, Kjetil B. Lund, Grigory G. Karateev, Kevin P. Francis, Elizabeth Allen, Juri G. Gelovani, Emmet McCormack, Mark Tangney, Elena A. Dubikovskaya
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10.1371/journal.pone.0055751

PLOS ONE Phosphorescent Imaging of Living Cells Using a Cyclometalated Iridium(III) Complex
February 14, 2013 Dik-Lung Ma, Hai-Jing Zhong, Wai-Chung Fu, Daniel Shiu-Hin Chan, Hiu-Yee Kwan, Wang-Fun Fong, Lai-Hon Chung, Chun-Yuen Wong, Chung-Hang Leung
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10.1371/journal.pone.0120982

PLOS ONE Co-Encapsulating the Fusogenic Peptide INF7 and Molecular Imaging Probes in Liposomes Increases Intracellular Signal and Probe Retention
March 27, 2015 Scott R. Burks, Eric A. Legenzov, Erik W. Martin, Changqing Li, Wuyuan Lu, Joseph P. Y. Kao
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10.1371/journal.pone.0160522

PLOS ONE Cathepsin Activity-Based Probes and Inhibitor for Preclinical Atherosclerosis Imaging and Macrophage Depletion
August 17, 2016 Ihab Abd-Elrahman, Hisanori Kosuge, Tommy Wises Sadan, Yael Ben-Nun, Karen Meir, Chen Rubinstein, Matthew Bogyo, Michael V. McConnell, Galia Blum
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10.1371/journal.pone.0121920

PLOS ONE SELEX Aptamer Used as a Probe to Detect Circulating Tumor Cells in Peripheral Blood of Pancreatic Cancer Patients
March 23, 2015 Jinqiang Zhang, Shaohua Li, Fang Liu, Lanping Zhou, Ningsheng Shao, Xiaohang Zhao
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10.1371/journal.pone.0129058

PLOS ONE New Small Molecules Targeting Apoptosis and Cell Viability in Osteosarcoma
June 3, 2015 Doris Maugg, Ina Rothenaigner, Kenji Schorpp, Harish Kumar Potukuchi, Eberhard Korsching, Daniel Baumhoer, Kamyar Hadian, Jan Smida, Michaela Nathrath
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10.1371/journal.pone.0125494

PLOS ONE Towards Fluorescence In Vivo Hybridization (FIVH) Detection of H. pylori in Gastric Mucosa Using Advanced LNA Probes
April 27, 2015 Sílvia Fontenete, Marina Leite, Nuno Guimarães, Pedro Madureira, Rui Manuel Ferreira, Céu Figueiredo, Jesper Wengel, Nuno Filipe Azevedo
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10.1371/journal.pone.0137410

PLOS ONE Mechanism of Action and Initial, In Vitro SAR of an Inhibitor of the Shigella flexneri Virulence Regulator VirF
September 9, 2015 Anthony A. Emanuele, George A. Garcia
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10.1371/journal.pone.0131330

PLOS ONE A Fluorescent Probe to Measure DNA Damage and Repair
August 26, 2015 Allison G. Condie, Yan Yan, Stanton L. Gerson, Yanming Wang
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10.1371/journal.pone.0161413

PLOS ONE Mitochondrial Probe Methyltriphenylphosphonium (TPMP) Inhibits the Krebs Cycle Enzyme 2-Oxoglutarate Dehydrogenase
August 18, 2016 Moustafa Elkalaf, Petr Tůma, Martin Weiszenstein, Jan Polák, Jan Trnka
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10.1371/journal.pone.0140927

PLOS ONE A Metabolic Probe-Enabled Strategy Reveals Uptake and Protein Targets of Polyunsaturated Aldehydes in the Diatom Phaeodactylum tricornutum
October 23, 2015 Stefanie Wolfram, Natalie Wielsch, Yvonne Hupfer, Bettina Mönch, Hui-Wen Lu-Walther, Rainer Heintzmann, Oliver Werz, Aleš Svatoš, Georg Pohnert

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