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Chembiochem : a European Journal of... Apr 2021RNA molecules can fold into complex two- and three-dimensional shapes that are critical for their function. Chemical probes have long been utilized to interrogate RNA... (Review)
Review
RNA molecules can fold into complex two- and three-dimensional shapes that are critical for their function. Chemical probes have long been utilized to interrogate RNA structure and are now considered invaluable resources in the goal of relating structure to function. Recently, the power of deep sequencing and careful chemical probe design have merged, permitting researchers to obtain a holistic understanding of how RNA structure can be utilized to control RNA biology transcriptome-wide. Within this review, we outline the recent advancements in chemical probe design for interrogating RNA structures inside cells and discuss the recent advances in our understanding of RNA biology through the lens of chemical probing.
Topics: DNA Adducts; DNA, Complementary; Molecular Probes; Nucleic Acid Conformation; RNA; RNA, Messenger; Transcriptome
PubMed: 32737940
DOI: 10.1002/cbic.202000340 -
The Analyst Nov 2021We have designed and synthesized a multifunctional dendritic molecular probe that selectively detects Cu ions potentiometric and fluorometric techniques with low...
We have designed and synthesized a multifunctional dendritic molecular probe that selectively detects Cu ions potentiometric and fluorometric techniques with low detection limits (3.5 μM in potentiometry, 15 nM in fluorometry). The selective and reversible binding of the molecule with the Cu ion was used to make a solid-state microsensor (diameter of 25 μm) by incorporating the molecular probe into the carbon-based membrane as an ionophore for Cu(II). The Cu(II) microelectrode has a broad linear range of 10 μM to 1 mM with a near Nernstian slope of 30 mV/log [] and detection limit of 3.5 μM. The Cu(II) microsensor has a fast response time (1.5 s), and it has a broad working pH range from 3.5 to 6.0. The incorporation of the hydrophobic dendritic moiety makes the ionophore less prone to leaching in an aqueous matrix for potentiometric measurement. The cinnamaldehyde component of the molecule helps detection of Cu ions fluorometrically, as indicated by a change in fluorescence upon selective and reversible binding of the molecular probe to the Cu ions. The strategic design of the molecular probe allows us to detect Cu ions in drinking water by using this novel dendritic fluoroionophore and solid-state Cu - ion-selective microelectrode.
Topics: Drinking Water; Fluorometry; Ions; Molecular Probes; Potentiometry
PubMed: 34591042
DOI: 10.1039/d1an01417j -
Future Medicinal Chemistry 2015Photoaffinity labeling (PAL) using a chemical probe to covalently bind its target in response to activation by light has become a frequently used tool in drug discovery... (Review)
Review
Photoaffinity labeling (PAL) using a chemical probe to covalently bind its target in response to activation by light has become a frequently used tool in drug discovery for identifying new drug targets and molecular interactions, and for probing the location and structure of binding sites. Methods to identify the specific target proteins of hit molecules from phenotypic screens are highly valuable in early drug discovery. In this review, we summarize the principles of PAL including probe design and experimental techniques for in vitro and live cell investigations. We emphasize the need to optimize and validate probes and highlight examples of the successful application of PAL across multiple disease areas.
Topics: Animals; Binding Sites; Drug Discovery; Humans; Molecular Probes; Photoaffinity Labels; Proteins
PubMed: 25686004
DOI: 10.4155/fmc.14.152 -
Current Topics in Medicinal Chemistry 2010Molecular imaging, the visualization, characterization and measurement of biological processes at the cellular, subcellular level, or even molecular level in living... (Review)
Review
Molecular imaging, the visualization, characterization and measurement of biological processes at the cellular, subcellular level, or even molecular level in living subjects, has rapidly gained importance in the dawning era of personalized medicine. Molecular imaging takes advantage of the traditional diagnostic imaging techniques and introduces molecular imaging probes to determine the expression of indicative molecular markers at different stages of diseases and disorders. As a key component of molecular imaging, molecular imaging probe must be able to specifically reach the target of interest in vivo while retaining long enough to be detected. A desirable molecular imaging probe with clinical translation potential is expected to have unique characteristics. Therefore, design and development of molecular imaging probe is frequently a challenging endeavor for medicinal chemists. This review summarizes the general principles of molecular imaging probe design and some fundamental strategies of molecular imaging probe development with a number of illustrative examples.
Topics: Humans; Molecular Imaging; Molecular Probes
PubMed: 20388106
DOI: 10.2174/156802610791384225 -
Scientific Reports Mar 2023Fibroblast activation protein (FAP) is higher expressed on cancer-associated fibroblasts (CAFs) in most malignant epithelial neoplasms, which is lower expressed in...
Fibroblast activation protein (FAP) is higher expressed on cancer-associated fibroblasts (CAFs) in most malignant epithelial neoplasms, which is lower expressed in normal tissues. As a promising small molecular probe, FAP inhibitor (FAPI) shows the specific binding to FAP. This study aimed to explore a novel molecular probe [Tc]Tc-HYNIC-FAPI targeting CAFs. The in vitro characteristics of the probe were also evaluated. The FAPI targeting FAP was designed, synthesized and conjugated with the chelator 6-hydrazinylnicotinic acid (HYNIC) for radiolabeling with Tc. The radiolabeling yield, radiochemical purity and stability were evaluated by Instant thin-layer chromatography (ITLC) and High performance liquid chromatography (HPLC). Lipophilicity was performed by the distribution coefficient test. The binding and migration ability of the probe was assessed using the FAP transfected tumor cell line. The radiolabeling yield of [Tc]Tc-HYNIC-FAPI was (97.29 ± 0.46) %. The radiochemical purity was more than 90% and kept stable until 6 h. The radioligand was shown as lower lipophilicity, of which logD7.4 value was - 2.38 [Formula: see text] 0.13. In vitro experiments, the results indicated that the probe showed binding properties, and inhibited the migration of tumor cells. The novel [Tc]Tc-HYNIC-FAPI probe was successfully radiosynthesized and exhibited good radiochemical purity, stability and in vitro binding ability to tumor cells. The [Tc]Tc-HYNIC-FAPI will be a promising SPECT/CT imaging probe.
Topics: Cancer-Associated Fibroblasts; Molecular Imaging; Single Photon Emission Computed Tomography Computed Tomography; Tomography, Emission-Computed, Single-Photon; Molecular Probes; Radiopharmaceuticals; Neoplasms
PubMed: 36879039
DOI: 10.1038/s41598-023-30806-6 -
ChemistryOpen Jul 2022Norepinephrine (NE), acting as both a neurotransmitter and hormone, plays a significant role in regulating the action of the brain and body. Many studies have...
Norepinephrine (NE), acting as both a neurotransmitter and hormone, plays a significant role in regulating the action of the brain and body. Many studies have demonstrated a strong correlation between mental disorders and aberrant NE levels. Therefore, it is of urgent demand to develop in vivo analytical methods of NE for diagnostic assessment and mechanistic investigations of mental diseases. Herein, we report a F MRI probe (NRFP) for sensing and imaging NE, which is constructed by conjugating a gadolinium chelate to a fluorine-containing moiety through a NE-responsive aromatic thiocarbonate linkage. The capacity and specificity of NRFP for detecting NE is validated with in vitro detecting/imaging experiments. Furthermore, the feasibility of NRFP for visualizing NE in animals is illustrated by ex vivo and in vivo imaging experiments, demonstrating the promising potential of NRFP for selective detection and specific imaging of NE in deep tissues of living subjects.
Topics: Animals; Contrast Media; Fluorine; Humans; Magnetic Resonance Imaging; Molecular Probes; Norepinephrine
PubMed: 35762743
DOI: 10.1002/open.202200110 -
Current Opinion in Chemical Biology Dec 2019Glycan-mediated interactions are essential in many biological processes and regulate a wide variety of cellular functions. However, characterizing these interactions is... (Review)
Review
Glycan-mediated interactions are essential in many biological processes and regulate a wide variety of cellular functions. However, characterizing these interactions is difficult because glycan biosynthesis is not template driven and because carbohydrate recognition events are usually of low affinity and transient. Photocrosslinking carbohydrate probes can form a covalent bond with molecules in close proximity on UV irradiation and are capable of capturing interactions between glycans and glycan-binding proteins in situ. Because of these advantages, multiple photocrosslinking carbohydrate probes have been designed and applied to study the biological functions of glycans. This review will discuss recent advances in the development of novel photocrosslinking functional groups and the design of photocrosslinking probes to detect interactions mediated by glycolipids, peptidoglycan, and multivalent carbohydrate ligands. These probes have demonstrated the potential to address some of the major challenges in the study of glycan-mediated interactions in both model systems and in more complex biological settings.
Topics: Carbohydrate Metabolism; Molecular Probes
PubMed: 31706134
DOI: 10.1016/j.cbpa.2019.09.002 -
Sensors (Basel, Switzerland) Jan 2014During the last decade, the development of nuclear spin polarization enhanced (hyperpolarized) molecular probes has opened up new opportunities for studying the inner... (Review)
Review
During the last decade, the development of nuclear spin polarization enhanced (hyperpolarized) molecular probes has opened up new opportunities for studying the inner workings of living cells in real time. The hyperpolarized probes are produced ex situ, introduced into biological systems and detected with high sensitivity and contrast against background signals using high resolution NMR spectroscopy. A variety of natural, derivatized and designed hyperpolarized probes has emerged for diverse biological studies including assays of intracellular reaction progression, pathway kinetics, probe uptake and export, pH, redox state, reactive oxygen species, ion concentrations, drug efficacy or oncogenic signaling. These probes are readily used directly under natural conditions in biofluids and are often directly developed and optimized for cellular assays, thus leaving little doubt about their specificity and utility under biologically relevant conditions. Hyperpolarized molecular probes for biological NMR spectroscopy enable the unbiased detection of complex processes by virtue of the high spectral resolution, structural specificity and quantifiability of NMR signals. Here, we provide a survey of strategies used for the selection, design and use of hyperpolarized NMR probes in biological assays, and describe current limitations and developments.
Topics: Biological Assay; Humans; Ions; Kinetics; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Molecular Probes
PubMed: 24441771
DOI: 10.3390/s140101576 -
Journal of Biomedical Optics Jul 2022Deep tissue noninvasive high-resolution imaging with light is challenging due to the high degree of light absorption and scattering in biological tissue. Photoacoustic... (Review)
Review
SIGNIFICANCE
Deep tissue noninvasive high-resolution imaging with light is challenging due to the high degree of light absorption and scattering in biological tissue. Photoacoustic imaging (PAI) can overcome some of the challenges of pure optical or ultrasound imaging to provide high-resolution deep tissue imaging. However, label-free PAI signals from light absorbing chromophores within the tissue are nonspecific. The use of exogeneous contrast agents (probes) not only enhances the imaging contrast (and imaging depth) but also increases the specificity of PAI by binding only to targeted molecules and often providing signals distinct from the background.
AIM
We aim to review the current development and future progression of photoacoustic molecular probes/contrast agents.
APPROACH
First, PAI and the need for using contrast agents are briefly introduced. Then, the recent development of contrast agents in terms of materials used to construct them is discussed. Then, various probes are discussed based on targeting mechanisms, molecular imaging applications, multimodal uses, and use in theranostic applications.
RESULTS
Material combinations are being used to develop highly specific contrast agents. In addition to passive accumulation, probes utilizing activation mechanisms show promise for greater controllability. Several probes also enable concurrent multimodal use with fluorescence, ultrasound, Raman, magnetic resonance imaging, and computed tomography. Finally, targeted probes are also shown to aid localized and molecularly specific photo-induced therapy.
CONCLUSIONS
The development of contrast agents provides a promising prospect for increased contrast, higher imaging depth, and molecularly specific information. Of note are agents that allow for controlled activation, explore other optical windows, and enable multimodal use to overcome some of the shortcomings of label-free PAI.
Topics: Molecular Probes; Contrast Media; Spectrum Analysis; Tomography, X-Ray Computed
PubMed: 36451698
DOI: 10.1117/1.JBO.27.7.070901 -
ACS Chemical Biology Dec 2021Over the past two decades, activity-based probes have enabled a range of discoveries, including the characterization of new enzymes and drug targets. However, their... (Review)
Review
Over the past two decades, activity-based probes have enabled a range of discoveries, including the characterization of new enzymes and drug targets. However, their suitability in some labeling experiments can be limited by nonspecific reactivity, poor membrane permeability, or high toxicity. One method for overcoming these issues is through the development of "inducible" activity-based probes. These probes are added to samples in an unreactive state and require transformation to their active form before labeling can occur. In this Review, we discuss a variety of approaches to inducible activity-based probe design, different means of probe activation, and the advancements that have resulted from these applications. Additionally, we highlight recent developments which may provide opportunities for future inducible activity-based probe innovations.
Topics: Fluorescent Dyes; Molecular Probes; Photochemical Processes; Protein Conformation; Proteins; Structure-Activity Relationship
PubMed: 34779621
DOI: 10.1021/acschembio.1c00572