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Philosophical Transactions. Series A,... Nov 2017Molecular imaging (MI), used in its wider sense of biology at the molecular level, is a field that lies at the intersection of molecular biology and traditional medical... (Review)
Review
Molecular imaging (MI), used in its wider sense of biology at the molecular level, is a field that lies at the intersection of molecular biology and traditional medical imaging. As advances in medicine have exponentially expanded over the last few decades, so has our need to better understand the fundamental behaviour of living organisms in a non-invasive and timely manner. This commentary draws from topics the authors addressed in their presentations at the 2017 Royal Society Meeting 'Challenges for chemistry in molecular imaging', as well as a discussion of where MI is today and where it is heading in the future.This article is part of the themed issue 'Challenges for chemistry in molecular imaging'.
Topics: Biomarkers; Humans; Inflammation; Molecular Imaging; Molecular Probe Techniques; Molecular Probes; Molecular Targeted Therapy; Multimodal Imaging; Precision Medicine; Surgery, Computer-Assisted
PubMed: 29038378
DOI: 10.1098/rsta.2017.0023 -
Small (Weinheim An Der Bergstrasse,... Jul 2022In vivo simultaneous visualization of multiple biomarkers is critical to accurately diagnose disease and decipher fundamental processes at a certain pathological...
In vivo simultaneous visualization of multiple biomarkers is critical to accurately diagnose disease and decipher fundamental processes at a certain pathological evolution, which however is rarely exploited. Herein, a multimodal activatable imaging probe (P- I) is reported with activatable fluoro-photoacoustic and radioactive signal for in vivo imaging of biomarkers (i.e., hepsin and prostate-specific membrane antigen (PSMA)) associated with prostate cancer diagnosis and prognosis. P- I contains a near-infrared (NIR) dye that is caged with a hepsin-cleavable peptide sequence and linked with a radiolabeled PSMA-targeted ligand (PSMAL). After systemic administration, P- I actively targets the tumor site via specific recognition between PSMA and PSMAL moiety and in-situ generates of activated fluoro-photoacoustic signal after reacting with hepsin to release the free dye (uncaged state). P- I achieves precisely early detection of prostate cancer and renal clearance to alleviate toxicity issues. In addition, the accumulated radioactive and activated photoacoustic signal of probe correlates well with the respective expression level of PSMA and hepsin, which provides valuable foreseeability for cancer progression and prognosis. Thus, this study presents a multimodal activatable probe for early detection and in-depth deciphering of prostate cancer.
Topics: Biomarkers, Tumor; Diagnostic Imaging; Fluorescent Dyes; Humans; Kidney; Male; Molecular Imaging; Molecular Probes; Prostatic Neoplasms
PubMed: 35723177
DOI: 10.1002/smll.202201334 -
Current Opinion in Chemical Biology Aug 2016The primary intent of a chemical probe is to establish the relationship between a molecular target, usually a protein whose function is modulated by the probe, and the... (Review)
Review
The primary intent of a chemical probe is to establish the relationship between a molecular target, usually a protein whose function is modulated by the probe, and the biological consequences of that modulation. In order to fulfill this purpose, a chemical probe must be profiled for selectivity, mechanism of action, and cellular activity, as the cell is the minimal system in which 'biology' can be explored. This review provides a brief overview of progress towards chemical probes for methyl lysine reader domains with a focus on recent progress targeting chromodomains.
Topics: Humans; Lysine; Methylation; Models, Molecular; Molecular Mimicry; Molecular Probes; Peptides
PubMed: 27348158
DOI: 10.1016/j.cbpa.2016.06.004 -
Molecules (Basel, Switzerland) Jan 2021A molecular probe with l-phenylalanine -nitroanilide and l-lysin 4-methylcoumaryl-7-amide, in which these amino acid derivatives are connected through a succinic-acid...
A molecular probe with l-phenylalanine -nitroanilide and l-lysin 4-methylcoumaryl-7-amide, in which these amino acid derivatives are connected through a succinic-acid spacer, was prepared. Trypsin and papain were detected by blue-fluorescence emission of generated 7-amino-4-methylcoumarin (AMC). α-Chymotrypsin and nattokinase were detected from both the blue-fluorescence emission of AMC and the UV absorbance of -nitroaniline. In addition, different time courses of -nitroaniline and AMC were observed between the reaction of with α-chymotrypsin and that with nattokinase. In the case of nattokinase, both the fluorescence emission and UV absorbance slowly increased. In contrast, the increasing UV absorbance was saturated at the early stage of the reaction of the present probe with chymotrypsin, whereas the fluorescence emission continuously increased in the following stages.
Topics: Aniline Compounds; Chymotrypsin; Fluorescent Dyes; Humans; Molecular Probes; Papain; Trypsin
PubMed: 33477543
DOI: 10.3390/molecules26020482 -
Journal of the American Chemical Society Mar 2021Post-translational modification of proteins with poly(ADP-ribose) (PAR) is an important component of the DNA damage response. Four PAR synthesis inhibitors have recently...
Post-translational modification of proteins with poly(ADP-ribose) (PAR) is an important component of the DNA damage response. Four PAR synthesis inhibitors have recently been approved for the treatment of breast, ovarian, and prostate cancers. Despite the clinical significance of PAR, a molecular understanding of its function, including its binding partners, remains incomplete. In this work, we synthesized a PAR photoaffinity probe that captures and isolates endogenous PAR binders. Our method identified dozens of known PAR-binding proteins and hundreds of novel candidates involved in DNA repair, RNA processing, and metabolism. PAR binding by eight candidates was confirmed using pull-down and/or electrophoretic mobility shift assays. Using PAR probes of defined lengths, we detected proteins that preferentially bind to 40-mer versus 8-mer PAR, indicating that polymer length may regulate the outcome and timing of PAR signaling pathways. This investigation produces the first census of PAR-binding proteins, provides a proteomics analysis of length-selective PAR binding, and associates PAR binding with RNA metabolism and the formation of biomolecular condensates.
Topics: Light; Molecular Probes; Poly-ADP-Ribose Binding Proteins; Proteomics; Signal Transduction
PubMed: 33596067
DOI: 10.1021/jacs.0c12246 -
Current Opinion in Chemical Biology Feb 2022Biological imaging and biosensing from subcellular/cellular level to whole body have enabled non-invasive visualisation of molecular events during various biological and... (Review)
Review
Biological imaging and biosensing from subcellular/cellular level to whole body have enabled non-invasive visualisation of molecular events during various biological and pathological processes, giving great contributions to the rapid and impressive advances in chemical biology, drug discovery, disease diagnosis and prognosis. Optical imaging features a series of merits, including convenience, high resolution, good sensitivity, low cost and the absence of ionizing radiation. Among different luminescent probes, metal-based molecules offer unique promise in optical bioimaging and biosensing in vitro and in vivo, arising from their small sizes, strong luminescence, large Stokes shifts, long lifetimes, high photostability and tunable toxicity. In this review, we aim to highlight the design of metal-based molecular probes from the standpoint of synthetic chemistry in the last 2 years for optical imaging, covering d-block transition metal and lanthanide complexes and multimodal imaging agents.
Topics: Biosensing Techniques; Diagnostic Imaging; Lanthanoid Series Elements; Luminescence; Molecular Probes; Transition Elements
PubMed: 34775149
DOI: 10.1016/j.cbpa.2021.102097 -
Chemical Society Reviews Jan 2022The real-time, dynamic optical visualization of lesions and margins ensures not only complete resection of the malignant tissues but also better preservation of the... (Review)
Review
The real-time, dynamic optical visualization of lesions and margins ensures not only complete resection of the malignant tissues but also better preservation of the vital organs/tissues during surgical procedures. Most imaging probes with an "always-on" signal encounter high background noise due to their non-specific accumulation in normal tissues. By contrast, activatable molecular probes only "turn on" their signals upon reaction with the targeted biomolecules that are overexpressed in malignant cells, offering high target-to-background ratios with high specificity and sensitivity. This review summarizes the recent progress of activatable molecular probes in surgical imaging and diagnosis. The design principle and mechanism of activatable molecular probes are discussed, followed by specific emphasis on applications ranging from fluorescence-guided surgery to endoscopy and tissue biopsy. Finally, potential challenges and perspectives in the field of activatable molecular probe-enabled surgical imaging are discussed.
Topics: Biopsy; Endoscopy; Fluorescent Dyes; Molecular Imaging; Molecular Probes; Optical Imaging
PubMed: 34928283
DOI: 10.1039/d1cs00525a -
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 -
Angewandte Chemie (International Ed. in... Oct 2021The surging development of bioorthogonal chemistry has profoundly transformed chemical biology over the last two decades. Involving chemical partners that specifically... (Review)
Review
The surging development of bioorthogonal chemistry has profoundly transformed chemical biology over the last two decades. Involving chemical partners that specifically react together in highly complex biological fluids, this branch of chemistry now allows researchers to probe biomolecules in their natural habitat through metabolic labelling technologies. Chemical reporter strategies include metabolic glycan labelling, site-specific incorporation of unnatural amino acids in proteins, and post-synthetic labelling of nucleic acids. While a majority of literature reports mark cell-surface exposed targets, implementing bioorthogonal ligations in the interior of cells constitutes a more challenging task. Owing to limiting factors such as membrane permeability of reagents, fluorescence background due to hydrophobic interactions and off-target covalent binding, and suboptimal balance between reactivity and stability of the designed molecular reporters and probes, these strategies need mindful planning to achieve success. In this review, we discuss the hurdles encountered when targeting biomolecules localized in cell organelles and give an easily accessible summary of the strategies at hand for imaging intracellular targets.
Topics: Alkynes; Animals; Azides; Bacteria; Cell Line, Tumor; Click Chemistry; Cycloaddition Reaction; Fluorescent Dyes; Humans; Molecular Probes; Nucleic Acids; Polysaccharides; Proteins
PubMed: 34097349
DOI: 10.1002/anie.202101502 -
Chemical Society Reviews Oct 2017Cyclodextrins (CDs) are naturally occurring cyclic oligosaccharides bearing a basket-shaped topology with an "inner-outer" amphiphilic character. The abundance of... (Review)
Review
Cyclodextrins (CDs) are naturally occurring cyclic oligosaccharides bearing a basket-shaped topology with an "inner-outer" amphiphilic character. The abundance of hydroxyl groups enables CDs to be functionalized with multiple targeting ligands and imaging elements. The imaging time, and the payload of different imaging elements, can be tuned by taking advantage of the commercial availability of CDs with different sizes of the cavity. This review aims to offer an outlook of the chemistry and engineering of CDs for the development of molecular probes. Complexation thermodynamics of CDs, and the corresponding implications for probe design, are also presented with examples demonstrating the structural and physiochemical roles played by CDs in the full ambit of molecular imaging. We hope that this review not only offers a synopsis of the current development of CD-based molecular probes, but can also facilitate translation of the incremental advancements from the laboratory to real biomedical applications by illuminating opportunities and challenges for future research.
Topics: Cyclodextrins; Molecular Imaging; Molecular Probes; Thermodynamics
PubMed: 28930330
DOI: 10.1039/c7cs00040e