molecules-logo

Journal Browser

Journal Browser

Feature Papers in Chemical BiologyEdition of 2022-2023

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

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 30236

Special Issue Editors

CSIC-UAM - Instituto de Investigaciones Biomédicas Alberto Sols (IIBM), Madrid, Spain
Interests: free radical biology; reactive oxygen species; reactive nitrogen species; peroxidases; NADH oxidases; lipidomics; intrinsically disordered proteins; neurodegenerative diseases; redox biomedicine
Special Issues, Collections and Topics in MDPI journals
Department of Pharmaceutical Technology and Chemistry, School of Pharmacy and Nutrition, University of Navarra, Irunlarrea 1, E-31008 Pamplona, Spain
Interests: Selenium; cancer; Leishmania; medicinal chemistry
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Due to the great success of the previous Special Issue titled “Feature Review Papers in Chemical Biology”, it is our pleasure to announce this edition for 2022 and 2023.

In this Special Issue, “Feature Papers in Chemical Biology 2022 and 2023”, we aim to publish articles within the field of chemical biology. While the definition of the field overlaps with medicinal and bioorganic chemistry, distinct aspects can be defined that earmark studies for this field, which is at the interface of chemistry and biology. Molecules are used to interfere with or visualize biological systems at the molecular level, which can lead to new insights into these systems and their biological mechanisms or can provide tools for their manipulation. Studies must include synthesized or isolated bioactive compounds or probes that realize the above goals. Studies in which compounds are described that capture or detect specific components in a biological context are also of interest.

Regarding the type of papers that will be considered, both research articles and comprehensive reviews are welcome for submission. Other types of high-quality papers will also be considered.

Dr. Alejandro Samhan-Arias
Prof. Dr. Carmen Sanmartín
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 submissions that pass pre-check are 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 2700 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 (16 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

18 pages, 4741 KiB  
Article
Molecular Insights into the Enhanced Activity and/or Thermostability of PET Hydrolase by D186 Mutations
by Zhi Qu, Lin Zhang and Yan Sun
Molecules 2024, 29(6), 1338; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules29061338 - 17 Mar 2024
Viewed by 459
Abstract
PETase exhibits a high degradation activity for polyethylene terephthalate (PET) plastic under moderate temperatures. However, the effect of non-active site residues in the second shell of PETase on the catalytic performance remains unclear. Herein, we proposed a crystal structure- and sequence-based strategy to [...] Read more.
PETase exhibits a high degradation activity for polyethylene terephthalate (PET) plastic under moderate temperatures. However, the effect of non-active site residues in the second shell of PETase on the catalytic performance remains unclear. Herein, we proposed a crystal structure- and sequence-based strategy to identify the key non-active site residue. D186 in the second shell of PETase was found to be capable of modulating the enzyme activity and stability. The most active PETaseD186N improved both the activity and thermostability with an increase in Tm by 8.89 °C. The PET degradation product concentrations were 1.86 and 3.69 times higher than those obtained with PETaseWT at 30 and 40 °C, respectively. The most stable PETaseD186V showed an increase in Tm of 12.91 °C over PETaseWT. Molecular dynamics (MD) simulations revealed that the D186 mutations could elevate the substrate binding free energy and change substrate binding mode, and/or rigidify the flexible Loop 10, and lock Loop 10 and Helix 6 by hydrogen bonding, leading to the enhanced activity and/or thermostability of PETase variants. This work unraveled the contribution of the key second-shell residue in PETase in influencing the enzyme activity and stability, which would benefit in the rational design of efficient and thermostable PETase. Full article
(This article belongs to the Special Issue Feature Papers in Chemical BiologyEdition of 2022-2023)
Show Figures

Graphical abstract

21 pages, 3956 KiB  
Article
Electrochemical Synthesis of New Isoxazoles and Triazoles Tethered with Thiouracil Base as Inhibitors of Histone Deacetylases in Human Breast Cancer Cells
by Divakar Vishwanath, Zhang Xi, Akshay Ravish, Arunkumar Mohan, Shreeja Basappa, Niranjan Pattehalli Krishnamurthy, Santosh L. Gaonkar, Vijay Pandey, Peter E. Lobie and Basappa Basappa
Molecules 2023, 28(13), 5254; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules28135254 - 06 Jul 2023
Cited by 3 | Viewed by 1467
Abstract
Histone deacetylases (HDACs) are an attractive drug target for the treatment of human breast cancer (BC), and therefore, HDAC inhibitors (HDACis) are being used in preclinical and clinical studies. The need to understand the scope of the mode of action of HDACis, as [...] Read more.
Histone deacetylases (HDACs) are an attractive drug target for the treatment of human breast cancer (BC), and therefore, HDAC inhibitors (HDACis) are being used in preclinical and clinical studies. The need to understand the scope of the mode of action of HDACis, as well as the report of the co-crystal structure of HDAC6/SS-208 at the catalytic site, provoked us to develop an isoxazole-based lead structure called 4-(2-(((1-(3,4-dichlorophenyl)-1H-1,2,3-triazol-4-yl)methyl)thio) pyrimidin-4-yl) morpholine (5h) and 1-(2-(((3-(p-tolyl) isoxazol-5-yl)methyl)thio) pyrimidin-4-yl) piperidin-4-one (6l) that targets HDACs in human BC cells. We found that the compound 5h or 6l could inhibit the proliferation of BC cells with an IC50 value of 8.754 and 11.71 µM, respectively. Our detailed in silico analysis showed that 5h or 6l compounds could target HDAC in MCF-7 cells. In conclusion, we identified a new structure bearing triazole, isoxazole, and thiouracil moiety, which could target HDAC in MCF-7 cells and serve as a base to make new drugs against cancer. Full article
(This article belongs to the Special Issue Feature Papers in Chemical BiologyEdition of 2022-2023)
Show Figures

Figure 1

18 pages, 2664 KiB  
Article
Coordination of the N-Terminal Heme in the Non-Classical Peroxidase from Escherichia coli
by Ricardo N. S. Oliveira, Sara R. M. M. de Aguiar and Sofia R. Pauleta
Molecules 2023, 28(12), 4598; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules28124598 - 07 Jun 2023
Viewed by 1130
Abstract
The non-classical bacterial peroxidase from Escherichia coli, YhjA, is proposed to deal with peroxidative stress in the periplasm when the bacterium is exposed to anoxic environments, defending it from hydrogen peroxide and allowing it to thrive under those conditions. This enzyme has [...] Read more.
The non-classical bacterial peroxidase from Escherichia coli, YhjA, is proposed to deal with peroxidative stress in the periplasm when the bacterium is exposed to anoxic environments, defending it from hydrogen peroxide and allowing it to thrive under those conditions. This enzyme has a predicted transmembrane helix and is proposed to receive electrons from the quinol pool in an electron transfer pathway involving two hemes (NT and E) to accomplish the reduction of hydrogen peroxide in the periplasm at the third heme (P). Compared with classical bacterial peroxidases, these enzymes have an additional N-terminal domain binding the NT heme. In the absence of a structure of this protein, several residues (M82, M125 and H134) were mutated to identify the axial ligand of the NT heme. Spectroscopic data demonstrate differences only between the YhjA and YhjA M125A variant. In the YhjA M125A variant, the NT heme is high-spin with a lower reduction potential than in the wild-type. Thermostability was studied by circular dichroism, demonstrating that YhjA M125A is thermodynamically more unstable than YhjA, with a lower TM (43 °C vs. 50 °C). These data also corroborate the structural model of this enzyme. The axial ligand of the NT heme was validated to be M125, and mutation of this residue was proven to affect the spectroscopic, kinetic, and thermodynamic properties of YhjA. Full article
(This article belongs to the Special Issue Feature Papers in Chemical BiologyEdition of 2022-2023)
Show Figures

Figure 1

11 pages, 1922 KiB  
Article
Cell-Free Expression of a Therapeutic Protein Serratiopeptidase
by Yaru Meng, Miaomiao Yang, Wanqiu Liu and Jian Li
Molecules 2023, 28(7), 3132; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules28073132 - 31 Mar 2023
Cited by 4 | Viewed by 1929
Abstract
Serratiopeptidase is a clinical therapeutic protein for the treatment of human diseases such as arthritis, bronchitis, and thrombosis. Yet production of this protein in a heterologous host (e.g., Escherichia coli) is difficult due to the issue of protein insolubility and the requirement [...] Read more.
Serratiopeptidase is a clinical therapeutic protein for the treatment of human diseases such as arthritis, bronchitis, and thrombosis. Yet production of this protein in a heterologous host (e.g., Escherichia coli) is difficult due to the issue of protein insolubility and the requirement of laborious refolding procedures. Cell-free protein synthesis (CFPS) systems, derived from crude cell extracts, are effective platforms for the expression of recombinant proteins in vitro. Here, we report a new method to produce serratiopeptidase by using an E. coli-based CFPS system. After rational selection of cell extracts and construction of expression vectors, soluble expression of serratiopeptidase was achieved and the enzyme activity could be readily tested in the cell-free reaction mixture. By further optimizing the key parameters, optimum conditions for the enzyme activity assay were obtained, including the pH value at 5, reaction temperature at 45 °C, substrate concentration at 10 mg/mL, and supplementing Ca2+ ions at 5 mM. Moreover, the CFPS mixture was freeze-dried and the activity of serratiopeptidase could be regenerated by hydration without losing activity. Overall, the CFPS system enabled soluble expression of serratiopeptidase with catalytic activity, providing a new and promising approach for this enzyme production. Our work extends the utility of the cell-free platform to produce therapeutic proteins with clinical applications. Full article
(This article belongs to the Special Issue Feature Papers in Chemical BiologyEdition of 2022-2023)
Show Figures

Figure 1

20 pages, 2548 KiB  
Article
Why Do These Yeasts Smell So Good? Volatile Organic Compounds (VOCs) Produced by Malassezia Species in the Exponential and Stationary Growth Phases
by Andrea Rios-Navarro, Mabel Gonzalez, Chiara Carazzone and Adriana Marcela Celis Ramírez
Molecules 2023, 28(6), 2620; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules28062620 - 14 Mar 2023
Viewed by 2020
Abstract
Malassezia synthesizes and releases volatile organic compounds (VOCs), small molecules that allow them to carry out interaction processes. These lipid-dependent yeasts belong to the human skin mycobiota and are related to dermatological diseases. However, knowledge about VOC production and its function is lacking. [...] Read more.
Malassezia synthesizes and releases volatile organic compounds (VOCs), small molecules that allow them to carry out interaction processes. These lipid-dependent yeasts belong to the human skin mycobiota and are related to dermatological diseases. However, knowledge about VOC production and its function is lacking. This study aimed to determine the volatile profiles of Malassezia globosa, Malassezia restricta, and Malassezia sympodialis in the exponential and stationary growth phases. The compounds were separated and characterized in each growth phase through headspace solid-phase microextraction (HS-SPME) and gas chromatography–mass spectrometry (GC–MS). We found a total of 54 compounds, 40 annotated. Most of the compounds identified belong to alcohols and polyols, fatty alcohols, alkanes, and unsaturated aliphatic hydrocarbons. Unsupervised and supervised statistical multivariate analyses demonstrated that the volatile profiles of Malassezia differed between species and growth phases, with M. globosa being the species with the highest quantity of VOCs. Some Malassezia volatiles, such as butan-1-ol, 2-methylbutan-1-ol, 3-methylbutan-1-ol, and 2-methylpropan-1-ol, associated with biological interactions were also detected. All three species show at least one unique compound, suggesting a unique metabolism. The ecological functions of the compounds detected in each species and growth phase remain to be studied. They could interact with other microorganisms or be an important clue in understanding the pathogenic role of these yeasts. Full article
(This article belongs to the Special Issue Feature Papers in Chemical BiologyEdition of 2022-2023)
Show Figures

Graphical abstract

13 pages, 2447 KiB  
Article
Novel Synthesis of IMC-48 and Affinity Evaluation with Different i-Motif DNA Sequences
by Florian Berthiol, Joseph Boissieras, Hugues Bonnet, Marie Pierrot, Christian Philouze, Jean-François Poisson, Anton Granzhan, Jérôme Dejeu and Eric Defrancq
Molecules 2023, 28(2), 682; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules28020682 - 10 Jan 2023
Cited by 3 | Viewed by 1693
Abstract
During the last decade, the evidence for the biological relevance of i-motif DNA (i-DNA) has been accumulated. However, relatively few molecules were reported to interact with i-DNA, and a controversy concerning their binding mode, affinity, and selectivity persists in the literature. In this [...] Read more.
During the last decade, the evidence for the biological relevance of i-motif DNA (i-DNA) has been accumulated. However, relatively few molecules were reported to interact with i-DNA, and a controversy concerning their binding mode, affinity, and selectivity persists in the literature. In this context, the cholestane derivative IMC-48 has been reported to modulate bcl-2 gene expression by stabilizing an i-motif structure in its promoter. In the present contribution, we report on a novel, more straightforward, synthesis of IMC-48 requiring fewer steps compared to the previous approach. Furthermore, the interaction of IMC-48 with four different i-motif DNA sequences was thoroughly investigated by bio-layer interferometry (BLI) and circular dichroism (CD) spectroscopy. Surprisingly, our results show that IMC-48 is a very weak ligand of i-DNA as no quantifiable interaction or significant stabilization of i-motif structures could be observed, stimulating a quest for an alternative mechanism of its biological activity. Full article
(This article belongs to the Special Issue Feature Papers in Chemical BiologyEdition of 2022-2023)
Show Figures

Graphical abstract

15 pages, 2854 KiB  
Article
The Use of Flavylium Salts as Dynamic Inhibitor Moieties for Human Cb5R
by Oscar H. Martínez-Costa, Laura Rodrigues-Miranda, Sofia M. Clemente, António Jorge Parola, Nuno Basilio and Alejandro K. Samhan-Arias
Molecules 2023, 28(1), 123; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules28010123 - 23 Dec 2022
Viewed by 1441
Abstract
Cytochrome b5 reductase (Cb5R) is a flavoprotein that participates in the reduction of multiple biological redox partners. Co-localization of this protein with nitric oxide sources has been observed in neurons. In addition, the generation of superoxide anion radical by [...] Read more.
Cytochrome b5 reductase (Cb5R) is a flavoprotein that participates in the reduction of multiple biological redox partners. Co-localization of this protein with nitric oxide sources has been observed in neurons. In addition, the generation of superoxide anion radical by Cb5R has been observed. A search for specific inhibitors of Cb5R to understand the role of this protein in these new functions has been initiated. Previous studies have shown the ability of different flavonoids to inhibit Cb5R. Anthocyanins are a subgroup of flavonoids responsible for most red and blue colors found in flowers and fruits. Although usually represented by the flavylium cation form, these species are only stable at rather acidic pH values (pH ≤ 1). At higher pH values, the flavylium cation is involved in a dynamic reaction network comprising different neutral species with the potential ability to inhibit the activities of Cb5R. This study aims to provide insights into the molecular mechanism of interaction between flavonoids and Cb5R using flavylium salts as dynamic inhibitors. The outcome of this study might lead to the design of improved specific enzyme inhibitors in the future. Full article
(This article belongs to the Special Issue Feature Papers in Chemical BiologyEdition of 2022-2023)
Show Figures

Figure 1

13 pages, 1996 KiB  
Article
Switching the N-Capping Region from all-L to all-D Amino Acids in a VEGF Mimetic Helical Peptide
by Lucia De Rosa, Donatella Diana, Domenica Capasso, Rachele Stefania, Rossella Di Stasi, Roberto Fattorusso and Luca Domenico D’Andrea
Molecules 2022, 27(20), 6982; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27206982 - 17 Oct 2022
Cited by 1 | Viewed by 1153
Abstract
The N-capping region of an α-helix is a short N-terminal amino acid stretch that contributes to nucleate and stabilize the helical structure. In the VEGF mimetic helical peptide QK, the N-capping region was previously demonstrated to be a key factor of QK helical [...] Read more.
The N-capping region of an α-helix is a short N-terminal amino acid stretch that contributes to nucleate and stabilize the helical structure. In the VEGF mimetic helical peptide QK, the N-capping region was previously demonstrated to be a key factor of QK helical folding. In this paper, we explored the effect of the chiral inversion of the N-capping sequence on QK folding, performing conformational analysis in solution by circular dichroism and NMR spectroscopy. The effect of such a modification on QK stability in serum and the proliferative effect were also evaluated. Full article
(This article belongs to the Special Issue Feature Papers in Chemical BiologyEdition of 2022-2023)
Show Figures

Figure 1

11 pages, 1596 KiB  
Article
A Molecular Mechanics Energy Partitioning Software for Biomolecular Systems
by Henrique S. Fernandes, Nuno M. F. S. A. Cerqueira, Sérgio F. Sousa and André Melo
Molecules 2022, 27(17), 5524; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27175524 - 27 Aug 2022
Cited by 2 | Viewed by 1647
Abstract
The partitioning of the molecular mechanics (MM) energy in calculations involving biomolecular systems is important to identify the source of major stabilizing interactions, e.g., in ligand–protein interactions, or to identify residues with considerable contributions in hybrid multiscale calculations, i.e., quantum mechanics/molecular mechanics (QM/MM). [...] Read more.
The partitioning of the molecular mechanics (MM) energy in calculations involving biomolecular systems is important to identify the source of major stabilizing interactions, e.g., in ligand–protein interactions, or to identify residues with considerable contributions in hybrid multiscale calculations, i.e., quantum mechanics/molecular mechanics (QM/MM). Here, we describe Energy Split, a software program to calculate MM energy partitioning considering the AMBER Hamiltonian and parameters. Energy Split includes a graphical interface plugin for VMD to facilitate the selection of atoms and molecules belonging to each part of the system. Energy Split is freely available at or can be easily installed through the VMD Store. Full article
(This article belongs to the Special Issue Feature Papers in Chemical BiologyEdition of 2022-2023)
Show Figures

Figure 1

16 pages, 3681 KiB  
Article
mTORC2 Is the Major Second Layer Kinase Negatively Regulating FOXO3 Activity
by Lucia Jimenez, Carlos Amenabar, Victor Mayoral-Varo, Thomas A. Mackenzie, Maria C. Ramos, Andreia Silva, Giampaolo Calissi, Inês Grenho, Carmen Blanco-Aparicio, Joaquin Pastor, Diego Megías, Bibiana I. Ferreira and Wolfgang Link
Molecules 2022, 27(17), 5414; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27175414 - 24 Aug 2022
Cited by 2 | Viewed by 2209
Abstract
Forkhead box O (FOXO) proteins are transcription factors involved in cancer and aging and their pharmacological manipulation could be beneficial for the treatment of cancer and healthy aging. FOXO proteins are mainly regulated by post-translational modifications including phosphorylation, acetylation and ubiquitination. As these [...] Read more.
Forkhead box O (FOXO) proteins are transcription factors involved in cancer and aging and their pharmacological manipulation could be beneficial for the treatment of cancer and healthy aging. FOXO proteins are mainly regulated by post-translational modifications including phosphorylation, acetylation and ubiquitination. As these modifications are reversible, activation and inactivation of FOXO factors is attainable through pharmacological treatment. One major regulatory input of FOXO signaling is mediated by protein kinases. Here, we use specific inhibitors against different kinases including PI3K, mTOR, MEK and ALK, and other receptor tyrosine kinases (RTKs) to determine their effect on FOXO3 activity. While we show that inhibition of PI3K efficiently drives FOXO3 into the cell nucleus, the dual PI3K/mTOR inhibitors dactolisib and PI-103 induce nuclear FOXO translocation more potently than the PI3Kδ inhibitor idelalisib. Furthermore, specific inhibition of mTOR kinase activity affecting both mTORC1 and mTORC2 potently induced nuclear translocation of FOXO3, while rapamycin, which specifically inhibits the mTORC1, failed to affect FOXO3. Interestingly, inhibition of the MAPK pathway had no effect on the localization of FOXO3 and upstream RTK inhibition only weakly induced nuclear FOXO3. We also measured the effect of the test compounds on the phosphorylation status of AKT, FOXO3 and ERK, on FOXO-dependent transcriptional activity and on the subcellular localization of other FOXO isoforms. We conclude that mTORC2 is the most important second layer kinase negatively regulating FOXO activity. Full article
(This article belongs to the Special Issue Feature Papers in Chemical BiologyEdition of 2022-2023)
Show Figures

Figure 1

15 pages, 3647 KiB  
Article
Counteractive Effects of Choline Geranate (CAGE) ILs and Ethanol on Insulin’s Stability—A Leap Forward towards Oral Insulin Formulation
by Kandhan Palanisamy and Muthuramalingam Prakash
Molecules 2022, 27(15), 5031; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27155031 - 08 Aug 2022
Cited by 1 | Viewed by 1575
Abstract
Choline geranate (CAGE) ionic liquids (ILs) stabilize insulin, thereby aiding its oral delivery, whereas ethanol (EtOH) affects its stability by disrupting the hydrophobic interactions. In this study, cognizance of the stabilization mechanism of insulin dimer in the presence of both CAGE ILs and [...] Read more.
Choline geranate (CAGE) ionic liquids (ILs) stabilize insulin, thereby aiding its oral delivery, whereas ethanol (EtOH) affects its stability by disrupting the hydrophobic interactions. In this study, cognizance of the stabilization mechanism of insulin dimer in the presence of both CAGE ILs and EtOH mixtures is achieved through biased and unbiased molecular dynamics (MD) simulations. Here, two order parameters are employed to study the insulin dimer dissociation using well-tempered metadynamics (WT-MetaD). The stability of insulin is found to be strongly maintained until a 0.20 mole fraction of EtOH. Besides, higher concentrations of EtOH marginally affect the insulin stability. Moreover, geranate anions form a higher number of H-bonding interactions with water molecules, which aids insulin stabilization. Conversely, the addition of EtOH minimizes the water-mediated H-bonding interactions of geranate. Additionally, geranate traps the EtOH molecules, thereby preventing the interactions between insulin and EtOH. Furthermore, the free energy landscape (FEL) reveals the absence of dimer dissociation along with noticeable deviations in the distances R and the number of contacts Q. The dimerization free energy of insulin was calculated to be −16.1 kcal/mol at a 0.20 mole fraction of EtOH. Moreover, increments in mole fractions of EtOH effectuate a decrease in the insulin stability. Thus, the present study represents CAGE ILs as efficient insulin dimer stabilizes at low concentrations of EtOH. Full article
(This article belongs to the Special Issue Feature Papers in Chemical BiologyEdition of 2022-2023)
Show Figures

Graphical abstract

28 pages, 6896 KiB  
Article
Folate-Targeted Curcumin-Loaded Niosomes for Site-Specific Delivery in Breast Cancer Treatment: In Silico and In Vitro Study
by Banafsheh Honarvari, Sara Karimifard, Niyayesh Akhtari, Mehrnoush Mehrarya, Zahra Salehi Moghaddam, Mohammad Javed Ansari, Abduladheem Turki Jalil, Adrián Matencio, Francesco Trotta, Faten Eshrati Yeganeh, Bahareh Farasati Far, Mandana Kazem Arki, Mohammad Reza Naimi-Jamal, Hassan Noorbazargan, Zahra Asghari Lalami and Mohsen Chiani
Molecules 2022, 27(14), 4634; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27144634 - 20 Jul 2022
Cited by 38 | Viewed by 2927
Abstract
As the most common cancer in women, efforts have been made to develop novel nanomedicine-based therapeutics for breast cancer. In the present study, the in silico curcumin (Cur) properties were investigated, and we found some important drawbacks of Cur. To enhance cancer therapeutics [...] Read more.
As the most common cancer in women, efforts have been made to develop novel nanomedicine-based therapeutics for breast cancer. In the present study, the in silico curcumin (Cur) properties were investigated, and we found some important drawbacks of Cur. To enhance cancer therapeutics of Cur, three different nonionic surfactants (span 20, 60, and 80) were used to prepare various Cur-loaded niosomes (Nio-Cur). Then, fabricated Nio-Cur were decorated with folic acid (FA) and polyethylene glycol (PEG) for breast cancer suppression. For PEG-FA@Nio-Cur, the gene expression levels of Bax and p53 were higher compared to free drug and Nio-Cur. With PEG-FA-decorated Nio-Cur, levels of Bcl2 were lower than the free drug and Nio-Cur. When MCF7 and 4T1 cell uptake tests of PEG-FA@Nio-Cur and Nio-Cur were investigated, the results showed that the PEG-FA-modified niosomes exhibited the most preponderant endocytosis. In vitro experiments demonstrate that PEG-FA@Nio-Cur is a promising strategy for the delivery of Cur in breast cancer therapy. Breast cancer cells absorbed the prepared nanoformulations and exhibited sustained drug release characteristics. Full article
(This article belongs to the Special Issue Feature Papers in Chemical BiologyEdition of 2022-2023)
Show Figures

Graphical abstract

16 pages, 4258 KiB  
Article
Euphorbiasteroid Abrogates EGFR and Wnt/β-Catenin Signaling in Non-Small-Cell Lung Cancer Cells to Impart Anticancer Activity
by Na Young Kim, Chakrabhavi Dhananjaya Mohan, Arunachalam Chinnathambi, Sulaiman Ali Alharbi, Gautam Sethi, Kanchugarakoppal S. Rangappa and Kwang Seok Ahn
Molecules 2022, 27(12), 3824; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules27123824 - 14 Jun 2022
Cited by 13 | Viewed by 1857
Abstract
EGFR and Wnt/β-catenin signaling pathways play a prominent role in tumor progression in various human cancers including non-small-cell lung carcinoma (NSCLC). Transactivation and crosstalk between the EGFR and Wnt/β-catenin pathways may contribute to the aggressiveness of cancers. Targeting these oncogenic pathways with small [...] Read more.
EGFR and Wnt/β-catenin signaling pathways play a prominent role in tumor progression in various human cancers including non-small-cell lung carcinoma (NSCLC). Transactivation and crosstalk between the EGFR and Wnt/β-catenin pathways may contribute to the aggressiveness of cancers. Targeting these oncogenic pathways with small molecules is an attractive approach to counteract various types of cancers. In this study, we demonstrate the effect of euphorbiasteroid (EPBS) on the EGFR and Wnt/β-catenin pathways in NSCLC cells. EPBS induced preferential cytotoxicity toward A549 (wildtype EGFR-expressing) cells over PC-9 (mutant EGFR-expressing) cells. EPBS suppressed the expression of EGFR, Wnt3a, β-catenin, and FZD-1, and the reduction in β-catenin levels was found to be mediated through the activation of GSK-3β. EPBS reduced the phosphorylation of GSK-3βS9 with a parallel increase in β-TrCP and phosphorylation of GSK-3βY216. Lithium chloride treatment increased the phosphorylation of GSK-3βS9 and nuclear localization of β-catenin, whereas EPBS reverted these effects. Forced expression or depletion of EGFR in NSCLC cells increased or decreased the levels of Wnt3a, β-catenin, and FZD-1, respectively. Overall, EPBS abrogates EGFR and Wnt/β-catenin pathways to impart its anticancer activity in NSCLC cells. Full article
(This article belongs to the Special Issue Feature Papers in Chemical BiologyEdition of 2022-2023)
Show Figures

Figure 1

Review

Jump to: Research

29 pages, 2372 KiB  
Review
The Microbial Degradation of Natural and Anthropogenic Phosphonates
by Francesca Ruffolo, Tamara Dinhof, Leanne Murray, Erika Zangelmi, Jason P. Chin, Katharina Pallitsch and Alessio Peracchi
Molecules 2023, 28(19), 6863; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules28196863 - 29 Sep 2023
Cited by 2 | Viewed by 1308
Abstract
Phosphonates are compounds containing a direct carbon–phosphorus (C–P) bond, which is particularly resistant to chemical and enzymatic degradation. They are environmentally ubiquitous: some of them are produced by microorganisms and invertebrates, whereas others derive from anthropogenic activities. Because of their chemical stability and [...] Read more.
Phosphonates are compounds containing a direct carbon–phosphorus (C–P) bond, which is particularly resistant to chemical and enzymatic degradation. They are environmentally ubiquitous: some of them are produced by microorganisms and invertebrates, whereas others derive from anthropogenic activities. Because of their chemical stability and potential toxicity, man-made phosphonates pose pollution problems, and many studies have tried to identify biocompatible systems for their elimination. On the other hand, phosphonates are a resource for microorganisms living in environments where the availability of phosphate is limited; thus, bacteria in particular have evolved systems to uptake and catabolize phosphonates. Such systems can be either selective for a narrow subset of compounds or show a broader specificity. The role, distribution, and evolution of microbial genes and enzymes dedicated to phosphonate degradation, as well as their regulation, have been the subjects of substantial studies. At least three enzyme systems have been identified so far, schematically distinguished based on the mechanism by which the C–P bond is ultimately cleaved—i.e., through either a hydrolytic, radical, or oxidative reaction. This review summarizes our current understanding of the molecular systems and pathways that serve to catabolize phosphonates, as well as the regulatory mechanisms that govern their activity. Full article
(This article belongs to the Special Issue Feature Papers in Chemical BiologyEdition of 2022-2023)
Show Figures

Graphical abstract

35 pages, 7481 KiB  
Review
Artificial Small Molecules as Cofactors and Biomacromolecular Building Blocks in Synthetic Biology: Design, Synthesis, Applications, and Challenges
by Fenghua Liu, Lingling He, Sheng Dong, Jinsong Xuan, Qiu Cui and Yingang Feng
Molecules 2023, 28(15), 5850; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules28155850 - 03 Aug 2023
Viewed by 1737
Abstract
Enzymes are essential catalysts for various chemical reactions in biological systems and often rely on metal ions or cofactors to stabilize their structure or perform functions. Improving enzyme performance has always been an important direction of protein engineering. In recent years, various artificial [...] Read more.
Enzymes are essential catalysts for various chemical reactions in biological systems and often rely on metal ions or cofactors to stabilize their structure or perform functions. Improving enzyme performance has always been an important direction of protein engineering. In recent years, various artificial small molecules have been successfully used in enzyme engineering. The types of enzymatic reactions and metabolic pathways in cells can be expanded by the incorporation of these artificial small molecules either as cofactors or as building blocks of proteins and nucleic acids, which greatly promotes the development and application of biotechnology. In this review, we summarized research on artificial small molecules including biological metal cluster mimics, coenzyme analogs (mNADs), designer cofactors, non-natural nucleotides (XNAs), and non-natural amino acids (nnAAs), focusing on their design, synthesis, and applications as well as the current challenges in synthetic biology. Full article
(This article belongs to the Special Issue Feature Papers in Chemical BiologyEdition of 2022-2023)
Show Figures

Graphical abstract

12 pages, 2758 KiB  
Review
Microbial Production of Human Milk Oligosaccharides
by Dileep Sai Kumar Palur, Shannon R. Pressley and Shota Atsumi
Molecules 2023, 28(3), 1491; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules28031491 - 03 Feb 2023
Cited by 2 | Viewed by 4288
Abstract
Human milk oligosaccharides (HMOs) are complex nonnutritive sugars present in human milk. These sugars possess prebiotic, immunomodulatory, and antagonistic properties towards pathogens and therefore are important for the health and well-being of newborn babies. Lower prevalence of breastfeeding around the globe, rising popularity [...] Read more.
Human milk oligosaccharides (HMOs) are complex nonnutritive sugars present in human milk. These sugars possess prebiotic, immunomodulatory, and antagonistic properties towards pathogens and therefore are important for the health and well-being of newborn babies. Lower prevalence of breastfeeding around the globe, rising popularity of nutraceuticals, and low availability of HMOs have inspired efforts to develop economically feasible and efficient industrial-scale production platforms for HMOs. Recent progress in synthetic biology and metabolic engineering tools has enabled microbial systems to be a production system of HMOs. In this regard, the model organism Escherichia coli has emerged as the preferred production platform. Herein, we summarize the remarkable progress in the microbial production of HMOs and discuss the challenges and future opportunities in unraveling the scope of production of complex HMOs. We focus on the microbial production of five HMOs that have been approved for their commercialization. Full article
(This article belongs to the Special Issue Feature Papers in Chemical BiologyEdition of 2022-2023)
Show Figures

Figure 1

Back to TopTop