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Special Issue "25th Anniversary of Molecules—Recent Advances in Chemical Biology"

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Chemical Biology".

Deadline for manuscript submissions: closed (1 November 2020).

Special Issue Editors

Prof. Dr. Steven Verhelst
Website
Guest Editor
Laboratory of Chemical Biology, Department of Cellular and Molecular Medicine, KU Leuven, Belgium
Interests: activity-based probes; activity-based protein profiling; bioorthogonal chemistry; chemical proteomics; cleavable linkers; intramembrane proteases; photoaffinity labeling; proteases; protease inhibitors
Special Issues and Collections in MDPI journals
Prof. Dr. Martin Witte
Website
Guest Editor
Stratingh Institute for Chemistry, University of Groningen, Groningen, The Netherlands
Interests: site-specific modification of proteins; chemoselective modification of carbohydrates; activity-based probes; chemical probes
Special Issues and Collections in MDPI journals
Prof. Dr. Aaron T. Wright
Website
Guest Editor
Senior Scientist & Group Leader, Chemical Biology & Exposure Sciences Group, Biological Sciences Division, Pacific Northwest National Laboratory, Richland WA 99352
Research Professor, The Gene and Linda Voiland School of Chemical Engineering & Bioengineering, Washington State University, Pullman WA 99163
Interests: chemical biology; target discovery; activity-based protein profiling; microbiomes; drug and xenobiotic metabolism; chemoproteomics; personalized medicine; vitamin B12/tetrapyrroles; photoaffinity labeling

Special Issue Information

Dear Colleagues,

In 2020, the journal Molecules is celebrating its 25th anniversary. To date, the journal has published more than 20,000 papers, and the journal website attracts 115,000 monthly visits and more than 395,000 monthly page views.

As guest editors, we would like to announce a Special Issue entitled “25th Anniversary of Molecules—Recent Advances in Chemical Biology” to mark this important milestone. This Special Issue will collect communications, research articles, and high-quality review papers in the research fields relating to chemical biology. We kindly encourage research groups working in various areas of chemical biology to make contributions to this Special Issue involving, but not restricted to: chemical probe design and synthesis, bioorthogonal reactions, target identification of chemical probes, and probe-mediated imaging in situ and in vivo.

Prof. Dr. Steven Verhelst
Prof. Martin Witte
Prof. Dr. Aaron T. Wright
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (8 papers)

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Research

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Open AccessArticle
Novel Biphenyl Amines Inhibit Oestrogen Receptor (ER)-α in ER-Positive Mammary Carcinoma Cells
Molecules 2021, 26(4), 783; https://doi.org/10.3390/molecules26040783 - 03 Feb 2021
Viewed by 399
Abstract
Herein, the activity of adamantanyl-tethered-biphenyl amines (ATBAs) as oestrogen receptor alpha (ERα) modulating ligands is reported. Using an ERα competitor assay it was demonstrated that ATBA compound 3-(adamantan-1-yl)-4-methoxy-N-(4-(trifluoromethyl) phenyl) aniline (AMTA) exhibited an inhibitory concentration 50% (IC50) value of 62.84 nM [...] Read more.
Herein, the activity of adamantanyl-tethered-biphenyl amines (ATBAs) as oestrogen receptor alpha (ERα) modulating ligands is reported. Using an ERα competitor assay it was demonstrated that ATBA compound 3-(adamantan-1-yl)-4-methoxy-N-(4-(trifluoromethyl) phenyl) aniline (AMTA) exhibited an inhibitory concentration 50% (IC50) value of 62.84 nM and demonstrated better binding affinity compared to tamoxifen (IC50 = 79.48 nM). Treatment of ERα positive (ER+) mammary carcinoma (MC) cells (Michigan Cancer Foundation-7 (MCF7)) with AMTA significantly decreased cell viability at an IC50 value of 6.4 μM. AMTA treatment of MC cell-generated three-dimensional (3D) spheroids resulted in significantly decreased cell viability. AMTA demonstrated a superior inhibitory effect compared to tamoxifen-treated MC cell spheroids. Subsequently, by use of an oestrogen response element (ERE) luciferase reporter construct, it was demonstrated that AMTA treatment significantly deceased ERE transcriptional activity in MC cells. Concordantly, AMTA treatment of MC cells also significantly decreased protein levels of oestrogen-regulated CCND1 in a dose-dependent manner. In silico molecular docking analysis suggested that AMTA compounds interact with the ligand-binding domain of ERα compared to the co-crystal ligand, 5-(4-hydroxyphenoxy)-6-(3-hydroxyphenyl)-7- methylnaphthalen-2-ol. Therefore, an analogue of AMTA may provide a structural basis to develop a newer class of ERα partial agonists. Full article
(This article belongs to the Special Issue 25th Anniversary of Molecules—Recent Advances in Chemical Biology)
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Open AccessArticle
The New Dipeptide TSPO Ligands: Design, Synthesis and Structure–Anxiolytic Activity Relationship
Molecules 2020, 25(21), 5132; https://doi.org/10.3390/molecules25215132 - 04 Nov 2020
Viewed by 382
Abstract
The translocator protein (TSPO, 18 kDa) plays an important role in the synthesis of neurosteroids by promoting the transport of cholesterol from the outer to the inner mitochondrial membrane, which is the rate-limiting step in neurosteroidogenesis. Stimulation of TSPO by appropriate ligands increases [...] Read more.
The translocator protein (TSPO, 18 kDa) plays an important role in the synthesis of neurosteroids by promoting the transport of cholesterol from the outer to the inner mitochondrial membrane, which is the rate-limiting step in neurosteroidogenesis. Stimulation of TSPO by appropriate ligands increases the level of neurosteroids. The present study describes the design, synthesis and investigation of anxiolytic-like effects of a series of N-acyl-tryptophanyl-containing dipeptides. These novel dipeptide TSPO ligands were designed with the original drug-based peptide design strategy using alpidem as non-peptide prototype. The anxiolytic activities were investigated in Balb/C mice using the illuminated open-field and elevated plus-maze tests in outbred laboratory mice ICR (CD-1). Dipeptide GD-102 (N-phenylpropionyl-l-tryptophanyl-l-leucine amide) in the dose range of 0.01–0.5 mg/kg intraperitoneally (i.p.) has a pronounced anxiolytic activity. The anxiolytic effect of GD-102 was abolished by PK11195, a specific TSPO antagonist. The structure–activity relationship study made it possible to identify a pharmacophore fragment for the dipeptide TSPO ligand. It was shown that l,d-diastereomer of GD-102 has no activity, and the d,l-isomer has less pronounced activity. The anxiolytic activity also disappears by replacing the C-amide group with the methyl ester, a free carboxyl group or methylamide. Consecutive replacement of each amino acid residue with glycine showed the importance of each of the amino acid residues in the structure of the ligand. The most active and technologically available compound GD-102, was selected for evaluation as a potential anxiolytic drug. Full article
(This article belongs to the Special Issue 25th Anniversary of Molecules—Recent Advances in Chemical Biology)
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Review

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Open AccessReview
Interrogating Plant-Microbe Interactions with Chemical Tools: Click Chemistry Reagents for Metabolic Labeling and Activity-Based Probes
Molecules 2021, 26(1), 243; https://doi.org/10.3390/molecules26010243 - 05 Jan 2021
Viewed by 534
Abstract
Continued expansion of the chemical biology toolbox presents many new and diverse opportunities to interrogate the fundamental molecular mechanisms driving complex plant–microbe interactions. This review will examine metabolic labeling with click chemistry reagents and activity-based probes for investigating the impacts of plant-associated microbes [...] Read more.
Continued expansion of the chemical biology toolbox presents many new and diverse opportunities to interrogate the fundamental molecular mechanisms driving complex plant–microbe interactions. This review will examine metabolic labeling with click chemistry reagents and activity-based probes for investigating the impacts of plant-associated microbes on plant growth, metabolism, and immune responses. While the majority of the studies reviewed here used chemical biology approaches to examine the effects of pathogens on plants, chemical biology will also be invaluable in future efforts to investigate mutualistic associations between beneficial microbes and their plant hosts. Full article
(This article belongs to the Special Issue 25th Anniversary of Molecules—Recent Advances in Chemical Biology)
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Open AccessReview
Recent Advances in Organelle-Targeted Fluorescent Probes
Molecules 2021, 26(1), 217; https://doi.org/10.3390/molecules26010217 - 04 Jan 2021
Viewed by 574
Abstract
Recent advances in fluorescence imaging techniques and super-resolution microscopy have extended the applications of fluorescent probes in studying various cellular processes at the molecular level. Specifically, organelle-targeted probes have been commonly used to detect cellular metabolites and transient chemical messengers with high precision [...] Read more.
Recent advances in fluorescence imaging techniques and super-resolution microscopy have extended the applications of fluorescent probes in studying various cellular processes at the molecular level. Specifically, organelle-targeted probes have been commonly used to detect cellular metabolites and transient chemical messengers with high precision and have become invaluable tools to study biochemical pathways. Moreover, several recent studies reported various labeling strategies and novel chemical scaffolds to enhance target specificity and responsiveness. In this review, we will survey the most recent reports of organelle-targeted fluorescent probes and assess their general strategies and structural features on the basis of their target organelles. We will discuss the advantages of the currently used probes and the potential challenges in their application as well as future directions. Full article
(This article belongs to the Special Issue 25th Anniversary of Molecules—Recent Advances in Chemical Biology)
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Open AccessReview
The Structure and Function of Paraoxonase-1 and Its Comparison to Paraoxonase-2 and -3
Molecules 2020, 25(24), 5980; https://doi.org/10.3390/molecules25245980 - 17 Dec 2020
Cited by 1 | Viewed by 407
Abstract
Serum paraoxonase-1 (PON1) is the most studied member of the group of paraoxonases (PONs). This enzyme possesses three enzymatic activities: lactonase, arylesterase, and paraoxonase activity. PON1 and its isoforms play an important role in drug metabolism as well as in the prevention of [...] Read more.
Serum paraoxonase-1 (PON1) is the most studied member of the group of paraoxonases (PONs). This enzyme possesses three enzymatic activities: lactonase, arylesterase, and paraoxonase activity. PON1 and its isoforms play an important role in drug metabolism as well as in the prevention of cardiovascular and neurodegenerative diseases. Although all three members of the PON family have the same origin and very similar amino acid sequences, they have different functions and are found in different locations. PONs exhibit substrate promiscuity, and their true physiological substrates are still not known. However, possible substrates include homocysteine thiolactone, an analogue of natural quorum-sensing molecules, and the recently discovered derivatives of arachidonic acid—bioactive δ-lactones. Directed evolution, site-directed mutagenesis, and kinetic studies provide comprehensive insights into the active site and catalytic mechanism of PON1. However, there is still a whole world of mystery waiting to be discovered, which would elucidate the substrate promiscuity of a group of enzymes that are so similar in their evolution and sequence yet so distinct in their function. Full article
(This article belongs to the Special Issue 25th Anniversary of Molecules—Recent Advances in Chemical Biology)
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Open AccessReview
From Phenotypic Hit to Chemical Probe: Chemical Biology Approaches to Elucidate Small Molecule Action in Complex Biological Systems
Molecules 2020, 25(23), 5702; https://doi.org/10.3390/molecules25235702 - 03 Dec 2020
Viewed by 737
Abstract
Biologically active small molecules have a central role in drug development, and as chemical probes and tool compounds to perturb and elucidate biological processes. Small molecules can be rationally designed for a given target, or a library of molecules can be screened against [...] Read more.
Biologically active small molecules have a central role in drug development, and as chemical probes and tool compounds to perturb and elucidate biological processes. Small molecules can be rationally designed for a given target, or a library of molecules can be screened against a target or phenotype of interest. Especially in the case of phenotypic screening approaches, a major challenge is to translate the compound-induced phenotype into a well-defined cellular target and mode of action of the hit compound. There is no “one size fits all” approach, and recent years have seen an increase in available target deconvolution strategies, rooted in organic chemistry, proteomics, and genetics. This review provides an overview of advances in target identification and mechanism of action studies, describes the strengths and weaknesses of the different approaches, and illustrates the need for chemical biologists to integrate and expand the existing tools to increase the probability of evolving screen hits to robust chemical probes. Full article
(This article belongs to the Special Issue 25th Anniversary of Molecules—Recent Advances in Chemical Biology)
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Open AccessReview
The Development of Maillard Reaction, and Advanced Glycation End Product (AGE)-Receptor for AGE (RAGE) Signaling Inhibitors as Novel Therapeutic Strategies for Patients with AGE-Related Diseases
Molecules 2020, 25(23), 5591; https://doi.org/10.3390/molecules25235591 - 27 Nov 2020
Viewed by 917
Abstract
Advanced glycation end products (AGEs) are generated by nonenzymatic modifications of macromolecules (proteins, lipids, and nucleic acids) by saccharides (glucose, fructose, and pentose) via Maillard reaction. The formed AGE molecules can be catabolized and cleared by glyoxalase I and II in renal proximal [...] Read more.
Advanced glycation end products (AGEs) are generated by nonenzymatic modifications of macromolecules (proteins, lipids, and nucleic acids) by saccharides (glucose, fructose, and pentose) via Maillard reaction. The formed AGE molecules can be catabolized and cleared by glyoxalase I and II in renal proximal tubular cells. AGE-related diseases include physiological aging, neurodegenerative/neuroinflammatory diseases, diabetes mellitus (DM) and its complications, autoimmune/rheumatic inflammatory diseases, bone-degenerative diseases, and chronic renal diseases. AGEs, by binding to receptors for AGE (RAGEs), alter innate and adaptive immune responses to induce inflammation and immunosuppression via the generation of proinflammatory cytokines, reactive oxygen species (ROS), and reactive nitrogen intermediates (RNI). These pathological molecules cause vascular endothelial/smooth muscular/connective tissue-cell and renal mesangial/endothelial/podocytic-cell damage in AGE-related diseases. In the present review, we first focus on the cellular and molecular bases of AGE–RAGE axis signaling pathways in AGE-related diseases. Then, we discuss in detail the modes of action of newly discovered novel biomolecules and phytochemical compounds, such as Maillard reaction and AGE–RAGE signaling inhibitors. These molecules are expected to become the new therapeutic strategies for patients with AGE-related diseases in addition to the traditional hypoglycemic and anti-hypertensive agents. We particularly emphasize the importance of “metabolic memory”, the “French paradox”, and the pharmacokinetics and therapeutic dosing of the effective natural compounds associated with pharmacogenetics in the treatment of AGE-related diseases. Lastly, we propose prospective investigations for solving the enigmas in AGE-mediated pathological effects. Full article
(This article belongs to the Special Issue 25th Anniversary of Molecules—Recent Advances in Chemical Biology)
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Open AccessReview
From Differential Stains to Next Generation Physiology: Chemical Probes to Visualize Bacterial Cell Structure and Physiology
Molecules 2020, 25(21), 4949; https://doi.org/10.3390/molecules25214949 - 26 Oct 2020
Cited by 1 | Viewed by 954
Abstract
Chemical probes have been instrumental in microbiology since its birth as a discipline in the 19th century when chemical dyes were used to visualize structural features of bacterial cells for the first time. In this review article we will illustrate the evolving design [...] Read more.
Chemical probes have been instrumental in microbiology since its birth as a discipline in the 19th century when chemical dyes were used to visualize structural features of bacterial cells for the first time. In this review article we will illustrate the evolving design of chemical probes in modern chemical biology and their diverse applications in bacterial imaging and phenotypic analysis. We will introduce and discuss a variety of different probe types including fluorogenic substrates and activity-based probes that visualize metabolic and specific enzyme activities, metabolic labeling strategies to visualize structural features of bacterial cells, antibiotic-based probes as well as fluorescent conjugates to probe biomolecular uptake pathways. Full article
(This article belongs to the Special Issue 25th Anniversary of Molecules—Recent Advances in Chemical Biology)
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