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Biological & Pharmaceutical Bulletin 2017In vivo molecular imaging is the visualization, characterization, and measurement of biological processes at the molecular and cellular levels in humans and other living... (Review)
Review
In vivo molecular imaging is the visualization, characterization, and measurement of biological processes at the molecular and cellular levels in humans and other living systems. Among the methodologies used in in vivo molecular imaging, two methodologies are of great interest from the view of high sensitivity. One is nuclear medical imaging, and distribution and kinetics of a radiolabeled molecular probe are measured using positron emission tomography (PET) and single-photon emission computed tomography (SPECT). The other is optical molecular imaging, and distribution and kinetics of a fluorescent probe are measured using a fluorescent imaging instrument. In this review, the development of imaging probes for these two methodologies is briefly discussed. In nuclear medical molecular imaging, based on structure-activity-biodistribution relationship studies for small molecule and the concept of "functional unit-binding multifunctional molecular probe" containing 3 functional units (target recognition unit, signal-releasing unit, linker unit) for peptides and proteins, we developed radiolabeled probes with high and specific accumulation to the target for neuroreceptors, β-amyloid plaques, and tau aggregates in the brain, tumors, atherosclerotic plaques, pancreatic β-cell, myocardial sympathetic nerves, and so on. We also discuss the progression of molecular imaging toward therapy (radiotheranotics). In in vivo optical molecular imaging, taking into account the characteristics of optical imaging, we designed tumor-specific optical imaging probes with characteristic imaging mechanism, including near-infrared (NIR) fluorescent probes and activatable probes. Furthermore, we developed a photoacoustic imaging probe, which enables highly sensitive and high-resolution imaging in deep tissues.
Topics: Animals; Fluorescent Dyes; Humans; Molecular Imaging; Molecular Probes
PubMed: 28966233
DOI: 10.1248/bpb.b17-00505 -
Cell Chemical Biology Aug 2020Dynamic proteins perform critical roles in cellular machines, including those that control proteostasis, transcription, translation, and signaling. Thus, dynamic... (Review)
Review
Dynamic proteins perform critical roles in cellular machines, including those that control proteostasis, transcription, translation, and signaling. Thus, dynamic proteins are prime candidates for chemical probe and drug discovery but difficult targets because they do not conform to classical rules of design and screening. Selectivity is pivotal for candidate probe molecules due to the extensive interaction network of these dynamic hubs. Recognition that the traditional rules of probe discovery are not necessarily applicable to dynamic proteins and their complexes, as well as technological advances in screening, have produced remarkable results in the last 2-4 years. Particularly notable are the improvements in target selectivity for small-molecule modulators of dynamic proteins, especially with techniques that increase the discovery likelihood of allosteric regulatory mechanisms. We focus on approaches to small-molecule screening that appear to be more suitable for highly dynamic targets and have the potential to streamline identification of selective modulators.
Topics: Allosteric Regulation; CREB-Binding Protein; HSP70 Heat-Shock Proteins; Models, Molecular; Molecular Probes; Protein Binding; Proteins; Small Molecule Libraries
PubMed: 32783965
DOI: 10.1016/j.chembiol.2020.07.019 -
Theranostics 2022Exploring and understanding the interaction of changes in the activities of various enzymes, such as proteases, phosphatases, and oxidoreductases with tumor invasion,... (Review)
Review
Exploring and understanding the interaction of changes in the activities of various enzymes, such as proteases, phosphatases, and oxidoreductases with tumor invasion, proliferation, and metastasis is of great significance for early cancer diagnosis. To detect the activity of tumor-related enzymes, various molecular probes have been developed with different imaging methods, including optical imaging, photoacoustic imaging (PAI), magnetic resonance imaging, positron emission tomography, and so on. In this review, we first describe the biological functions of various enzymes and the selectively recognized chemical linkers or groups. Subsequently, we systematically summarize the design mechanism of imaging probes and different imaging methods. Finally, we explore the challenges and development prospects in the field of enzyme activity detection. This comprehensive review will provide more insight into the design and development of enzyme activated molecular probes.
Topics: Humans; Molecular Imaging; Molecular Probes; Neoplasms; Optical Imaging; Photoacoustic Techniques; Tomography, X-Ray Computed
PubMed: 35154500
DOI: 10.7150/thno.66676 -
Cell Chemical Biology Apr 2020Ferroptosis is a recently described form of cell death driven by iron-dependent lipid peroxidation. This type of cell death was first observed in response to treatment... (Review)
Review
Ferroptosis is a recently described form of cell death driven by iron-dependent lipid peroxidation. This type of cell death was first observed in response to treatment of tumor cells with a small-molecule chemical probe named erastin. Most subsequent advances in understanding the mechanisms governing ferroptosis involved the use of genetic screens and small-molecule probes. We describe herein the utility and limitations of chemical probes that have been used to analyze and perturb ferroptosis, as well as mechanistic studies of ferroptosis that benefitted from the use of these probes and genetic screens. We also suggest probes for ferroptosis and highlight mechanistic questions surrounding this form of cell death that will be a high priority for exploration in the future.
Topics: Amino Acid Transport System y+; Energy Metabolism; Ferroptosis; Humans; Iron; Lipid Peroxidation; Molecular Probes; Neoplasms; Phospholipid Hydroperoxide Glutathione Peroxidase; Signal Transduction
PubMed: 32294465
DOI: 10.1016/j.chembiol.2020.03.013 -
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 -
Frontiers in Immunology 2022Cancer immunotherapy, especially immune-checkpoint inhibitors (ICIs), has paved a new way for the treatment of many types of malignancies, particularly advanced-stage... (Review)
Review
Cancer immunotherapy, especially immune-checkpoint inhibitors (ICIs), has paved a new way for the treatment of many types of malignancies, particularly advanced-stage cancers. Accumulating evidence suggests that as a molecular imaging modality, positron emission tomography/computed tomography (PET/CT) can play a vital role in the management of ICIs therapy by using different molecular probes and metabolic parameters. In this review, we will provide a comprehensive overview of the clinical data to support the importance of F-fluorodeoxyglucose PET/CT (F-FDG PET/CT) imaging in the treatment of ICIs, including the evaluation of the tumor microenvironment, discovery of immune-related adverse events, evaluation of therapeutic efficacy, and prediction of therapeutic prognosis. We also discuss perspectives on the development direction of F-FDG PET/CT imaging, with a particular emphasis on possible challenges in the future. In addition, we summarize the researches on novel PET molecular probes that are expected to potentially promote the precise application of ICIs.
Topics: Humans; Positron Emission Tomography Computed Tomography; Fluorodeoxyglucose F18; Immune Checkpoint Inhibitors; Neoplasms; Molecular Imaging; Molecular Probes; Tumor Microenvironment
PubMed: 36341331
DOI: 10.3389/fimmu.2022.1049043 -
Proceedings of the National Academy of... Aug 2023Trehalose plays a crucial role in the survival and virulence of the deadly human pathogen (). The type I ATP-binding cassette (ABC) transporter LpqY-SugABC is the sole...
Trehalose plays a crucial role in the survival and virulence of the deadly human pathogen (). The type I ATP-binding cassette (ABC) transporter LpqY-SugABC is the sole pathway for trehalose to enter . The substrate-binding protein, LpqY, which forms a stable complex with the translocator SugABC, recognizes and captures trehalose and its analogues in the periplasmic space, but the precise molecular mechanism for this process is still not well understood. This study reports a 3.02-Å cryoelectron microscopy structure of trehalose-bound LpqY-SugABC in the pretranslocation state, a crystal structure of LpqY in a closed form with trehalose bound and five crystal structures of LpqY in complex with different trehalose analogues. These structures, accompanied by substrate-stimulated ATPase activity data, reveal how LpqY recognizes and binds trehalose and its analogues, and highlight the flexibility in the substrate binding pocket of LpqY. These data provide critical insights into the design of trehalose analogues that could serve as potential molecular probe tools or as anti-TB drugs.
Topics: Humans; Cryoelectron Microscopy; Mycobacterium tuberculosis; Trehalose; ATP-Binding Cassette Transporters; Molecular Probes
PubMed: 37603751
DOI: 10.1073/pnas.2307625120 -
Zhejiang Da Xue Xue Bao. Yi Xue Ban =... Feb 2021Neuroendocrine tumors are a type of heterogeneous tumors originating from neuroendocrine cells derived from the neural crest,which can secrete a variety of amines and... (Review)
Review
Neuroendocrine tumors are a type of heterogeneous tumors originating from neuroendocrine cells derived from the neural crest,which can secrete a variety of amines and peptide hormones.Based on different molecular biomarkers,histologic types and differentiation degrees,individualized nuclear imaging can provide information for the early diagnosis,clinical staging,treatment guidance,and detection of the recurrence and metastasis of neuroendocrine tumor. In this paper,we review the development and application of nuclear medicine molecular imaging probes such as glucose analogs,somatostatin analogues,amine precursors,hormone analogs and enzyme inhibitors in the diagnosis and treatment of neuroendocrine tumors.
Topics: Diagnostic Imaging; Humans; Molecular Probes; Neoplasm Recurrence, Local; Neuroendocrine Tumors; Radionuclide Imaging
PubMed: 34117850
DOI: 10.3724/zdxbyxb-2021-0031 -
Dalton Transactions (Cambridge, England... Oct 2017The development of new methods to image the onset and progression of thrombosis is an unmet need. Non-invasive molecular imaging techniques targeting specific key... (Review)
Review
The development of new methods to image the onset and progression of thrombosis is an unmet need. Non-invasive molecular imaging techniques targeting specific key structures involved in the formation of thrombosis have demonstrated the ability to detect thrombus in different disease state models and in patients. Due to its high concentration in the thrombus and its essential role in thrombus formation, the detection of fibrin is an attractive strategy for identification of thrombosis. Herein we provide an overview of recent and selected fibrin-targeted probes for molecular imaging of thrombosis by magnetic resonance imaging (MRI), positron emission tomography (PET), single photon emission computed tomography (SPECT), and optical techniques. Emphasis is placed on work that our lab has explored over the last 15 years that has resulted in the progression of the fibrin-binding PET probe [Cu]FBP8 from preclinical studies into human trials.
Topics: Animals; Fibrin; Humans; Molecular Imaging; Molecular Probes; Peptides; Thrombosis
PubMed: 29051933
DOI: 10.1039/c7dt02634j -
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