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2019 Feature Papers by Biomolecules’ Editorial Board Members
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2019 Feature Papers by Biomolecules’ Editorial Board Members

A special issue of Biomolecules (ISSN 2218-273X).

Deadline for manuscript submissions: closed (31 December 2019) | Viewed by 77961

Special Issue Editor

Prof. Dr. Vladimir N. Uversky

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Guest Editor
Department of Molecular Medicine, USF Health Byrd Alzheimer’s Research Institute, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Blvd, MDC07, Tampa, FL 33612, USA
Interests: intrinsically disordered proteins; protein folding; protein misfolding; partially folded proteins; protein aggregation; protein structure; protein function; protein stability; protein biophysics; protein bioinformatics; conformational diseases; protein–ligand interactions; protein–protein interactions; liquid-liquid phase transitions
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue of Biomolecules represents a collection of papers submitted exclusively by its Editorial Board Members (EBMs). By representing different areas of research on biomolecules conducted in the laboratories its EBMs, this Special Issue introduces Biomolecules as a first-class platform for reporting scientific data. With this Special Issue, we also want to celebrate ranking of Biomolecules as 29/402 (Q1) in 'Biochemistry' and 40/366 (Q1) in 'Molecular Biology' based on the CiteScore 2017 (Scopus) of 5.83, as well as forthcoming release of our first impact factor (IF), which we earned by many years of hard work, dedication, and commitment from our EBMs.

Authors can submit their manuscripts online at www.mdpi.com by registering and logging in the following website: https://susy.mdpi.com/user/login. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website.

Dr. Vladimir N. Uversky
Guest Editor

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. Biomolecules is an international peer-reviewed open access monthly 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 (17 papers)

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Editorial

Jump to: Research, Review

2 pages, 155 KiB  
Editorial
Biomolecules from Different Angles
by Vladimir N. Uversky
Biomolecules 2021, 11(1), 14; https://0-doi-org.brum.beds.ac.uk/10.3390/biom11010014 - 26 Dec 2020
Viewed by 1684
Abstract
Special Issue “2019 Feature Papers by Biomolecules’ Editorial Board Members” represents a set of papers based on the results of the research in the laboratories of the Editorial Board Members (EBMs) of Biomolecules focused (a big surprise!) on different aspects of biomolecules [...] Read more.
Special Issue “2019 Feature Papers by Biomolecules’ Editorial Board Members” represents a set of papers based on the results of the research in the laboratories of the Editorial Board Members (EBMs) of Biomolecules focused (a big surprise!) on different aspects of biomolecules [...] Full article
(This article belongs to the Special Issue 2019 Feature Papers by Biomolecules’ Editorial Board Members)

Research

Jump to: Editorial, Review

7 pages, 1036 KiB  
Communication
Macromolecular Crowding Increases the Affinity of the PHD of ING4 for the Histone H3K4me3 Mark
by Alicia Palacios and Francisco J Blanco
Biomolecules 2020, 10(2), 234; https://0-doi-org.brum.beds.ac.uk/10.3390/biom10020234 - 04 Feb 2020
Cited by 4 | Viewed by 2761
Abstract
The five members of the family of tumor suppressors ING contain a Plant Homeodomain (PHD) that specifically recognizes histone H3 trimethylated at lysine 4 (H3K4me3) with an affinity in the low micromolar range. Here, we use NMR to show that in the presence [...] Read more.
The five members of the family of tumor suppressors ING contain a Plant Homeodomain (PHD) that specifically recognizes histone H3 trimethylated at lysine 4 (H3K4me3) with an affinity in the low micromolar range. Here, we use NMR to show that in the presence of 15% Ficoll 70, an inert macromolecular crowding agent, the mode of binding does not change but the affinity increases by one order of magnitude. The affinity increases also for unmethylated histone H3 tail, but the difference with H3K4me3 is larger in the presence of Ficoll. These results indicate that in the cellular milieu, the affinity of the ING proteins for their chromatin target is larger than previously thought. Full article
(This article belongs to the Special Issue 2019 Feature Papers by Biomolecules’ Editorial Board Members)
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14 pages, 2534 KiB  
Article
General and Genomic DNA-Binding Specificity for the Thermus thermophilus HB8 Transcription Factor TTHB023
by James Shell Cox and Michael W. Van Dyke
Biomolecules 2020, 10(1), 94; https://0-doi-org.brum.beds.ac.uk/10.3390/biom10010094 - 06 Jan 2020
Cited by 5 | Viewed by 2362
Abstract
Transcription factors are proteins that recognize specific DNA sequences and affect local transcriptional processes. They are the primary means by which all organisms control specific gene expression. Understanding which DNA sequences a particular transcription factor recognizes provides important clues into the set of [...] Read more.
Transcription factors are proteins that recognize specific DNA sequences and affect local transcriptional processes. They are the primary means by which all organisms control specific gene expression. Understanding which DNA sequences a particular transcription factor recognizes provides important clues into the set of genes that they regulate and, through this, their potential biological functions. Insights may be gained through homology searches and genetic means. However, these approaches can be misleading, especially when comparing distantly related organisms or in cases of complicated transcriptional regulation. In this work, we used a biochemistry-based approach to determine the spectrum of DNA sequences specifically bound by the Thermus thermophilus HB8 TetR-family transcription factor TTHB023. The consensus sequence 5′–(a/c)Y(g/t)A(A/C)YGryCR(g/t)T(c/a)R(g/t)–3′ was found to have a nanomolar binding affinity with TTHB023. Analyzing the T. thermophilus HB8 genome, several TTHB023 consensus binding sites were mapped to the promoters of genes involved in fatty acid biosynthesis. Notably, some of these were not identified previously through genetic approaches, ostensibly given their potential co-regulation by the Thermus thermophilus HB8 TetR-family transcriptional repressor TTHA0167. Our investigation provides additional evidence supporting the usefulness of a biochemistry-based approach for characterizing putative transcription factors, especially in the case of cooperative regulation. Full article
(This article belongs to the Special Issue 2019 Feature Papers by Biomolecules’ Editorial Board Members)
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12 pages, 1876 KiB  
Article
Voltage Sensing in Bacterial Protein Translocation
by Denis G. Knyazev, Roland Kuttner, Ana-Nicoleta Bondar, Mirjam Zimmerman, Christine Siligan and Peter Pohl
Biomolecules 2020, 10(1), 78; https://0-doi-org.brum.beds.ac.uk/10.3390/biom10010078 - 03 Jan 2020
Cited by 10 | Viewed by 2433
Abstract
The bacterial channel SecYEG efficiently translocates both hydrophobic and hydrophilic proteins across the plasma membrane. Translocating polypeptide chains may dislodge the plug, a half helix that blocks the permeation of small molecules, from its position in the middle of the aqueous translocation channel. [...] Read more.
The bacterial channel SecYEG efficiently translocates both hydrophobic and hydrophilic proteins across the plasma membrane. Translocating polypeptide chains may dislodge the plug, a half helix that blocks the permeation of small molecules, from its position in the middle of the aqueous translocation channel. Instead of the plug, six isoleucines in the middle of the membrane supposedly seal the channel, by forming a gasket around the translocating polypeptide. However, this hypothesis does not explain how the tightness of the gasket may depend on membrane potential. Here, we demonstrate voltage-dependent closings of the purified and reconstituted channel in the presence of ligands, suggesting that voltage sensitivity may be conferred by motor protein SecA, ribosomes, signal peptides, and/or translocating peptides. Yet, the presence of a voltage sensor intrinsic to SecYEG was indicated by voltage driven closure of pores that were forced-open either by crosslinking the plug to SecE or by plug deletion. We tested the involvement of SecY’s half-helix 2b (TM2b) in voltage sensing, since clearly identifiable gating charges are missing. The mutation L80D accelerated voltage driven closings by reversing TM2b’s dipolar orientation. In contrast, the L80K mutation decelerated voltage induced closings by increasing TM2b’s dipole moment. The observations suggest that TM2b is part of a larger voltage sensor. By partly aligning the combined dipole of this sensor with the orientation of the membrane-spanning electric field, voltage may drive channel closure. Full article
(This article belongs to the Special Issue 2019 Feature Papers by Biomolecules’ Editorial Board Members)
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15 pages, 1532 KiB  
Article
Naphtho-Gamma-Pyrones Produced by Aspergillus tubingensis G131: New Source of Natural Nontoxic Antioxidants
by Quentin Carboué, Marc Maresca, Gaëtan Herbette, Sevastianos Roussos, Rayhane Hamrouni and Isabelle Bombarda
Biomolecules 2020, 10(1), 29; https://0-doi-org.brum.beds.ac.uk/10.3390/biom10010029 - 24 Dec 2019
Cited by 11 | Viewed by 2589
Abstract
Seven naphtho-gamma-pyrones (NγPs), including asperpyrone E, aurasperone A, dianhydroaurasperone C, fonsecin, fonsecinone A, fonsecin B, and ustilaginoidin A, were isolated from Aspergillus tubingensis G131, a non-toxigenic strain. The radical scavenging activity of these NγPs was evaluated using ABTS assay. The Trolox equivalent antioxidant [...] Read more.
Seven naphtho-gamma-pyrones (NγPs), including asperpyrone E, aurasperone A, dianhydroaurasperone C, fonsecin, fonsecinone A, fonsecin B, and ustilaginoidin A, were isolated from Aspergillus tubingensis G131, a non-toxigenic strain. The radical scavenging activity of these NγPs was evaluated using ABTS assay. The Trolox equivalent antioxidant capacity on the seven isolated NγPs ranged from 2.4 to 14.6 μmol L−1. The toxicity and ability of the NγPs to prevent H2O2-mediated cell death were evaluated using normal/not cancerous cells (CHO cells). This cell-based assay showed that NγPs: (1) Are not toxic or weakly toxic towards cells and (2) are able to protect cells from oxidant injuries with an IC50 on H2O2-mediated cell death ranging from 2.25 to 1800 μmol mL−1. Our data show that A. tubingensis G131 strain is able to produce various NγPs possessing strong antioxidant activities and low toxicities, making this strain a good candidate for antioxidant applications in food and cosmetic industries. Full article
(This article belongs to the Special Issue 2019 Feature Papers by Biomolecules’ Editorial Board Members)
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31 pages, 9147 KiB  
Article
Designer Amyloid Cell-Penetrating Peptides for Potential Use as Gene Transfer Vehicles
by Chrysoula Kokotidou, Sai Vamshi R. Jonnalagadda, Asuka A. Orr, George Vrentzos, Androniki Kretsovali, Phanourios Tamamis and Anna Mitraki
Biomolecules 2020, 10(1), 7; https://0-doi-org.brum.beds.ac.uk/10.3390/biom10010007 - 18 Dec 2019
Cited by 15 | Viewed by 4568
Abstract
Cell-penetrating peptides are used extensively to deliver molecules into cells due to their unique characteristics such as rapid internalization, charge, and non-cytotoxicity. Amyloid fibril biomaterials were reported as gene transfer or retroviral infection enhancers; no cell internalization of the peptides themselves is reported [...] Read more.
Cell-penetrating peptides are used extensively to deliver molecules into cells due to their unique characteristics such as rapid internalization, charge, and non-cytotoxicity. Amyloid fibril biomaterials were reported as gene transfer or retroviral infection enhancers; no cell internalization of the peptides themselves is reported so far. In this study, we focus on two rationally and computationally designed peptides comprised of β-sheet cores derived from naturally occurring protein sequences and designed positively charged and aromatic residues exposed at key residue positions. The β-sheet cores bestow the designed peptides with the ability to self-assemble into amyloid fibrils. The introduction of positively charged and aromatic residues additionally promotes DNA condensation and cell internalization by the self-assembled material formed by the designed peptides. Our results demonstrate that these designer peptide fibrils can efficiently enter mammalian cells while carrying packaged luciferase-encoding plasmid DNA, and they can act as a protein expression enhancer. Interestingly, the peptides additionally exhibited strong antimicrobial activity against the enterobacterium Escherichia coli. Full article
(This article belongs to the Special Issue 2019 Feature Papers by Biomolecules’ Editorial Board Members)
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18 pages, 2827 KiB  
Article
Generation of Lamprey Monoclonal Antibodies (Lampribodies) Using the Phage Display System
by Khan M. A. Hassan, John D. Hansen, Brantley R. Herrin and Chris T. Amemiya
Biomolecules 2019, 9(12), 868; https://0-doi-org.brum.beds.ac.uk/10.3390/biom9120868 - 12 Dec 2019
Cited by 3 | Viewed by 5044
Abstract
The variable lymphocyte receptors (VLRs) consist of leucine rich repeats (LRRs) and comprise the humoral antibodies produced by lampreys and hagfishes. The diversity of the molecules is generated by stepwise genomic rearrangements of LRR cassettes dispersed throughout the VLRB locus. Previously, target-specific monovalent [...] Read more.
The variable lymphocyte receptors (VLRs) consist of leucine rich repeats (LRRs) and comprise the humoral antibodies produced by lampreys and hagfishes. The diversity of the molecules is generated by stepwise genomic rearrangements of LRR cassettes dispersed throughout the VLRB locus. Previously, target-specific monovalent VLRB antibodies were isolated from sea lamprey larvae after immunization with model antigens. Further, the cloned VLR cDNAs from activated lamprey leukocytes were transfected into human cell lines or yeast to select best binders. Here, we expand on the overall utility of the VLRB technology by introducing it into a filamentous phage display system. We first tested the efficacy of isolating phage into which known VLRB molecules were cloned after a series of dilutions. These experiments showed that targeted VLRB clones could easily be recovered even after extensive dilutions (1 to 109). We further utilized the system to isolate target-specific “lampribodies” from phage display libraries from immunized animals and observed an amplification of binders with relative high affinities by competitive binding. The lampribodies can be individually purified and ostensibly utilized for applications for which conventional monoclonal antibodies are employed. Full article
(This article belongs to the Special Issue 2019 Feature Papers by Biomolecules’ Editorial Board Members)
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14 pages, 664 KiB  
Article
N-glycomic Profile in Combat Related Post-Traumatic Stress Disorder
by Lucija Tudor, Gordana Nedic Erjavec, Matea Nikolac Perkovic, Marcela Konjevod, Dubravka Svob Strac, Suzana Uzun, Oliver Kozumplik, Tanja Jovanovic, Gordan Lauc and Nela Pivac
Biomolecules 2019, 9(12), 834; https://0-doi-org.brum.beds.ac.uk/10.3390/biom9120834 - 06 Dec 2019
Cited by 13 | Viewed by 2673
Abstract
Post-traumatic stress disorder (PTSD) develops in a portion of individuals exposed to extreme trauma. Glycosylation is a post-translational modification that affects protein functions and is altered in various pathophysiological states and aging. There are still no validated biomarkers of PTSD. The aim of [...] Read more.
Post-traumatic stress disorder (PTSD) develops in a portion of individuals exposed to extreme trauma. Glycosylation is a post-translational modification that affects protein functions and is altered in various pathophysiological states and aging. There are still no validated biomarkers of PTSD. The aim of this study was to evaluate the N-glycomic profile in 543 male Caucasian individuals (299 veterans with PTSD and 244 control subjects). The study included discovery (N = 233) and replication (N = 310) cohort. Hydrophilic interaction HPLC and ultra-performance liquid chromatography were used to separate and detect 39 plasma and 24 IgG N-glycan species, respectively. All results were corrected for the effects of age and multiple testing. Significant results included only significantly altered N-glycans in cases/controls in both cohorts, in the same direction. Results showed that six plasma N-glycans (four increased and two decreased) were altered in PTSD vs. controls in both cohorts, but IgG N-glycans were similar between groups. The severity of PTSD was not associated with different plasma N-glycans. This is the first study detecting alterations in plasma N-glycans in PTSD. These N-glycans are also associated with other neuropsychiatric disorders and inflammation, suggesting possible shared glycosylation mechanisms. Full article
(This article belongs to the Special Issue 2019 Feature Papers by Biomolecules’ Editorial Board Members)
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13 pages, 1154 KiB  
Article
Effects of Synergistic Inhibition on α-glucosidase by Phytoalexins in Soybeans
by Hyeong-U Son, Eun-Kyeong Yoon, Chi-Yeol Yoo, Chul-Hong Park, Myung-Ae Bae, Tae-Ho Kim, Chang Hyung Lee, Ki Won Lee, Hogyun Seo, Kyung-Jin Kim and Sang-Han Lee
Biomolecules 2019, 9(12), 828; https://0-doi-org.brum.beds.ac.uk/10.3390/biom9120828 - 05 Dec 2019
Cited by 21 | Viewed by 4449
Abstract
To determine the mechanism of action of the effects of phytoalexins in soybeans, we analyzed α-glucosidase inhibition kinetics using Michaelis–Menten plots and Lineweaver–Burk plots. The results showed that the type of inhibition with glyceollin was competitive, that of genistein was noncompetitive, that [...] Read more.
To determine the mechanism of action of the effects of phytoalexins in soybeans, we analyzed α-glucosidase inhibition kinetics using Michaelis–Menten plots and Lineweaver–Burk plots. The results showed that the type of inhibition with glyceollin was competitive, that of genistein was noncompetitive, that of daidzein was uncompetitive, and luteolin showed a mixed mode of action. The Ki values were determined using a Dixon plot as glyceollin, 18.99 μM; genistein, 15.42 μM; luteolin, 16.81 μM; and daidzein, 9.99 μM. Furthermore, potential synergistic effects between glyceollin and the three polyphenols were investigated. A combination of glyceollin and luteolin at a ratio of 3:7 exhibited synergistic effects on α-glucosidase inhibition, having a combination index (CI) of 0.64244, according to the CI–isobologram equation. Collectively, these results showed that a combination of glyceollin and luteolin has the potential to inhibit α-glucosidase activity via a synergistic mode of inhibition. Full article
(This article belongs to the Special Issue 2019 Feature Papers by Biomolecules’ Editorial Board Members)
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22 pages, 2780 KiB  
Article
Effect of Caffeine and Other Methylxanthines on Aβ-Homeostasis in SH-SY5Y Cells
by Daniel Janitschke, Christopher Nelke, Anna Andrea Lauer, Liesa Regner, Jakob Winkler, Andrea Thiel, Heike Sabine Grimm, Tobias Hartmann and Marcus Otto Walter Grimm
Biomolecules 2019, 9(11), 689; https://0-doi-org.brum.beds.ac.uk/10.3390/biom9110689 - 02 Nov 2019
Cited by 20 | Viewed by 6322
Abstract
Methylxanthines (MTX) are alkaloids derived from the purine-base xanthine. Whereas especially caffeine, the most prominent known MTX, has been formerly assessed to be detrimental, this point of view has changed substantially. MTXs are discussed to have beneficial properties in neurodegenerative diseases, however, the [...] Read more.
Methylxanthines (MTX) are alkaloids derived from the purine-base xanthine. Whereas especially caffeine, the most prominent known MTX, has been formerly assessed to be detrimental, this point of view has changed substantially. MTXs are discussed to have beneficial properties in neurodegenerative diseases, however, the mechanisms of action are not completely understood. Here we investigate the effect of the naturally occurring caffeine, theobromine and theophylline and the synthetic propentofylline and pentoxifylline on processes involved in Alzheimer’s disease (AD). All MTXs decreased amyloid-β (Aβ) level by shifting the amyloid precursor protein (APP) processing from the Aβ-producing amyloidogenic to the non-amyloidogenic pathway. The α-secretase activity was elevated whereas β-secretase activity was decreased. Breaking down the molecular mechanism, caffeine increased protein stability of the major α-secretase ADAM10, downregulated BACE1 expression and directly decreased β-secretase activity. Additionally, APP expression was reduced. In line with literature, MTXs reduced oxidative stress, decreased cholesterol and a decreased in Aβ1-42 aggregation. In conclusion, all MTXs act via the pleiotropic mechanism resulting in decreased Aβ and show beneficial properties with respect to AD in neuroblastoma cells. However, the observed effect strength was moderate, suggesting that MTXs should be integrated in a healthy diet rather than be used exclusively to treat or prevent AD. Full article
(This article belongs to the Special Issue 2019 Feature Papers by Biomolecules’ Editorial Board Members)
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20 pages, 3167 KiB  
Article
Hinge Region in DNA Packaging Terminase pUL15 of Herpes Simplex Virus: A Potential Allosteric Target for Antiviral Drugs
by Lana F. Thaljeh, J. Ainsley Rothschild, Misagh Naderi, Lyndon M. Coghill, Jeremy M. Brown and Michal Brylinski
Biomolecules 2019, 9(10), 603; https://0-doi-org.brum.beds.ac.uk/10.3390/biom9100603 - 12 Oct 2019
Cited by 5 | Viewed by 3423
Abstract
Approximately 80% of adults are infected with a member of the herpesviridae family. Herpesviruses establish life-long latent infections within neurons, which may reactivate into lytic infections due to stress or immune suppression. There are nine human herpesviruses (HHV) posing health concerns from benign [...] Read more.
Approximately 80% of adults are infected with a member of the herpesviridae family. Herpesviruses establish life-long latent infections within neurons, which may reactivate into lytic infections due to stress or immune suppression. There are nine human herpesviruses (HHV) posing health concerns from benign conditions to life threatening encephalitis, including cancers associated with viral infections. The current treatment options for most HHV conditions mainly include several nucleoside and nucleotide analogs targeting viral DNA polymerase. Although these drugs help manage infections, their common mechanism of action may lead to the development of drug resistance, which is particularly devastating in immunocompromised patients. Therefore, new classes of drugs directed against novel targets in HHVs are necessary to alleviate this issue. We analyzed the conservation rates of all proteins in herpes simplex virus 1 (HHV-1), a representative of the HHV family and one of the most common viruses infecting the human population. Furthermore, we generated a full-length structure model of the most conserved HHV-1 protein, the DNA packaging terminase pUL15. A series of computational analyses were performed on the model to identify ATP and DNA binding sites and characterize the dynamics of the protein. Our study indicates that proteins involved in HHV-1 DNA packaging and cleavage are amongst the most conserved gene products of HHVs. Since the packaging protein pUL15 is the most conserved among all HHV-1 gene products, the virus will have a lower chance of developing resistance to small molecules targeting pUL15. A subsequent analysis of the structure of pUL15 revealed distinct ATP and DNA binding domains and the elastic network model identifies a functionally important hinge region between the two domains of pUL15. The atomic information on the active and allosteric sites in the ATP- and DNA-bound model of pUL15 presented in this study can inform the structure-based drug discovery of a new class of drugs to treat a wide range of HHVs. Full article
(This article belongs to the Special Issue 2019 Feature Papers by Biomolecules’ Editorial Board Members)
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15 pages, 3064 KiB  
Article
Kinetic Transition in Amyloid Assembly as a Screening Assay for Oligomer-Selective Dyes
by Jeremy Barton, D. Sebastian Arias, Chamani Niyangoda, Gustavo Borjas, Nathan Le, Saefallah Mohamed and Martin Muschol
Biomolecules 2019, 9(10), 539; https://0-doi-org.brum.beds.ac.uk/10.3390/biom9100539 - 27 Sep 2019
Cited by 12 | Viewed by 4530
Abstract
Assembly of amyloid fibrils and small globular oligomers is associated with a significant number of human disorders that include Alzheimer’s disease, senile systemic amyloidosis, and type II diabetes. Recent findings implicate small amyloid oligomers as the dominant aggregate species mediating the toxic effects [...] Read more.
Assembly of amyloid fibrils and small globular oligomers is associated with a significant number of human disorders that include Alzheimer’s disease, senile systemic amyloidosis, and type II diabetes. Recent findings implicate small amyloid oligomers as the dominant aggregate species mediating the toxic effects in these disorders. However, validation of this hypothesis has been hampered by the dearth of experimental techniques to detect, quantify, and discriminate oligomeric intermediates from late-stage fibrils, in vitro and in vivo. We have shown that the onset of significant oligomer formation is associated with a transition in thioflavin T kinetics from sigmoidal to biphasic kinetics. Here we showed that this transition can be exploited for screening fluorophores for preferential responses to oligomer over fibril formation. This assay identified crystal violet as a strongly selective oligomer-indicator dye for lysozyme. Simultaneous recordings of amyloid kinetics with thioflavin T and crystal violet enabled us to separate the combined signals into their underlying oligomeric and fibrillar components. We provided further evidence that this screening assay could be extended to amyloid-β peptides under physiological conditions. Identification of oligomer-selective dyes not only holds the promise of biomedical applications but provides new approaches for unraveling the mechanisms underlying oligomer versus fibril formation in amyloid assembly. Full article
(This article belongs to the Special Issue 2019 Feature Papers by Biomolecules’ Editorial Board Members)
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12 pages, 4382 KiB  
Communication
A Comparative Evaluation of the Antiproliferative Activity against HepG2 Liver Carcinoma Cells of Plant-Derived Silver Nanoparticles from Basil Extracts with Contrasting Anthocyanin Contents
by Bilal Haider Abbasi, Munazza Nazir, Wali Muhammad, Syed Salman Hashmi, Rashda Abbasi, Lubna Rahman and Christophe Hano
Biomolecules 2019, 9(8), 320; https://0-doi-org.brum.beds.ac.uk/10.3390/biom9080320 - 30 Jul 2019
Cited by 30 | Viewed by 4200
Abstract
Nanotechnology is a well-established and revolutionized field with diverse therapeutic properties. Several methods have been employed using different reducing agents to synthesize silver nanoparticles (AgNPs). Chemical mediated synthetic methods are toxic and resulted in non-desired effects on biological systems. Herein, we, synthesized silver [...] Read more.
Nanotechnology is a well-established and revolutionized field with diverse therapeutic properties. Several methods have been employed using different reducing agents to synthesize silver nanoparticles (AgNPs). Chemical mediated synthetic methods are toxic and resulted in non-desired effects on biological systems. Herein, we, synthesized silver nanoparticles using callus extract of purple basil (BC-AgNPs) and anthocyanin extract deriving from the same plant (i.e., purple basil) (AE-AgNPs), and systematically investigated their antiproliferative potential against HepG2 Liver Carcinoma Cells. The phyto-fabricated AgNPs were characterized by different techniques like UV–visible spectroscopy (UV-Vis), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), Scanning electron microscopy (SEM) and Energy dispersive X-rays (EDX). Morphologically, both types of NPs were found spherical. The average size of BC-AgNPs and AE-AgNPs as revealed through XRD and SEM analyses were calculated as 50.97 ± 0.10 nm and 42.73 ± 1.24 nm, respectively. FT-IR spectral analysis demonstrates the existence of possible phytochemicals required for the capping and reduction of Ag ions. Herein, following solid phase extraction (SPE) coupled to HPLC analysis, we report for the first-time the anthocyanin mediated synthesis of AgNPs and conforming the successful capping of anthocyanin. Small sized AE-AgNPs showed significant cytotoxic effect against human hepatocellular carcinoma (HepG2) cell line as compared to BC-AgNPs. Therefore, the results revealed that the prevalent group of flavonoids present in purple basil is the anthocyanins and AE-AgNPs could be employed as potential anticancer agents in future treatments strategies. Full article
(This article belongs to the Special Issue 2019 Feature Papers by Biomolecules’ Editorial Board Members)
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15 pages, 893 KiB  
Article
Assessment of DNA Topoisomerase I Unwinding Activity, Radical Scavenging Capacity, and Inhibition of Breast Cancer Cell Viability of N-alkyl-acridones and N,N′-dialkyl-9,9′-biacridylidenes
by Marios G. Krokidis, Zara Molphy, Eleni K. Efthimiadou, Marianna Kokoli, Smaragda-Maria Argyri, Irini Dousi, Annalisa Masi, Kyriakos Papadopoulos, Andrew Kellett and Chryssostomos Chatgilialoglu
Biomolecules 2019, 9(5), 177; https://0-doi-org.brum.beds.ac.uk/10.3390/biom9050177 - 08 May 2019
Cited by 8 | Viewed by 4261
Abstract
The anticancer activity of acridone derivatives has attracted increasing interest, therefore, a variety of substituted analogs belonging to this family have been developed and evaluated for their anti-cancer properties. A series of N-alkyl-acridones 1–6 and N,N′-dialkyl-9,9′-biacridylidenes 7 [...] Read more.
The anticancer activity of acridone derivatives has attracted increasing interest, therefore, a variety of substituted analogs belonging to this family have been developed and evaluated for their anti-cancer properties. A series of N-alkyl-acridones 1–6 and N,N′-dialkyl-9,9′-biacridylidenes 7–12 with variable alkyl chains were examined for their topoisomerase I activity at neutral and acidic conditions as well as for their binding capacity to calf thymus and possible radical trapping antioxidant activity. It was found that at a neutral pH, topoisomerase I activity of both classes of compounds was similar, while under acidic conditions, enhanced intercalation was observed. N-alkyl-acridone derivatives 1–6 exhibited stronger, dose-dependent, cytotoxic activity against MCF-7 human breast epithelial cancer cells than N,N′-dialkyl-9,9′-biacridylidenes 7–12, revealing that conjugation of the heteroaromatic system plays a significant role on the effective distribution of the compound in the intracellular environment. Cellular investigation of long alkyl derivatives against cell migration exhibited 40–50% wound healing effects and cytoplasm diffusion, while compounds with shorter alkyl chains were accumulated both in the nucleus and cytoplasm. All N,N′-dialkyl-9,9′-biacridylidenes showed unexpected high scavenging activity towards DPPH or ABTS radicals which may be explained by higher stabilization of radical cations by the extended conjugation of heteroaromatic ring system. Full article
(This article belongs to the Special Issue 2019 Feature Papers by Biomolecules’ Editorial Board Members)
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Review

Jump to: Editorial, Research

46 pages, 972 KiB  
Review
Prosopis Plant Chemical Composition and Pharmacological Attributes: Targeting Clinical Studies from Preclinical Evidence
by Javad Sharifi-Rad, Farzad Kobarfard, Athar Ata, Seyed Abdulmajid Ayatollahi, Nafiseh Khosravi-Dehaghi, Arun Kumar Jugran, Merve Tomas, Esra Capanoglu, Karl R. Matthews, Jelena Popović-Djordjević, Aleksandar Kostić, Senem Kamiloglu, Farukh Sharopov, Muhammad Iqbal Choudhary and Natália Martins
Biomolecules 2019, 9(12), 777; https://0-doi-org.brum.beds.ac.uk/10.3390/biom9120777 - 25 Nov 2019
Cited by 33 | Viewed by 7469
Abstract
Members of the Prosopis genus are native to America, Africa and Asia, and have long been used in traditional medicine. The Prosopis species most commonly used for medicinal purposes are P. africana, P. alba, P. cineraria, P. farcta, P. [...] Read more.
Members of the Prosopis genus are native to America, Africa and Asia, and have long been used in traditional medicine. The Prosopis species most commonly used for medicinal purposes are P. africana, P. alba, P. cineraria, P. farcta, P. glandulosa, P. juliflora, P. nigra, P. ruscifolia and P. spicigera, which are highly effective in asthma, birth/postpartum pains, callouses, conjunctivitis, diabetes, diarrhea, expectorant, fever, flu, lactation, liver infection, malaria, otitis, pains, pediculosis, rheumatism, scabies, skin inflammations, spasm, stomach ache, bladder and pancreas stone removal. Flour, syrup, and beverages from Prosopis pods have also been potentially used for foods and food supplement formulation in many regions of the world. In addition, various in vitro and in vivo studies have revealed interesting antiplasmodial, antipyretic, anti-inflammatory, antimicrobial, anticancer, antidiabetic and wound healing effects. The phytochemical composition of Prosopis plants, namely their content of C-glycosyl flavones (such as schaftoside, isoschaftoside, vicenin II, vitexin and isovitexin) has been increasingly correlated with the observed biological effects. Thus, given the literature reports, Prosopis plants have positive impact on the human diet and general health. In this sense, the present review provides an in-depth overview of the literature data regarding Prosopis plants’ chemical composition, pharmacological and food applications, covering from pre-clinical data to upcoming clinical studies. Full article
(This article belongs to the Special Issue 2019 Feature Papers by Biomolecules’ Editorial Board Members)
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52 pages, 6072 KiB  
Review
Natural Products and Synthetic Analogs as a Source of Antitumor Drugs
by Javad Sharifi-Rad, Adem Ozleyen, Tugba Boyunegmez Tumer, Charles Oluwaseun Adetunji, Nasreddine El Omari, Abdelaali Balahbib, Yasaman Taheri, Abdelhakim Bouyahya, Miquel Martorell, Natália Martins and William C. Cho
Biomolecules 2019, 9(11), 679; https://0-doi-org.brum.beds.ac.uk/10.3390/biom9110679 - 01 Nov 2019
Cited by 132 | Viewed by 8419
Abstract
Cancer is a heterogeneous disease and one of the major issues of health concern, especially for the public health system globally. Nature is a source of anticancer drugs with abundant pool of diverse chemicals and pharmacologically active compounds. In recent decade, some natural [...] Read more.
Cancer is a heterogeneous disease and one of the major issues of health concern, especially for the public health system globally. Nature is a source of anticancer drugs with abundant pool of diverse chemicals and pharmacologically active compounds. In recent decade, some natural products and synthetic analogs have been investigated for the cancer treatment. This article presents the utilization of natural products as a source of antitumor drugs. Full article
(This article belongs to the Special Issue 2019 Feature Papers by Biomolecules’ Editorial Board Members)
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27 pages, 1479 KiB  
Review
Acute vs. Chronic vs. Cyclic Hypoxia: Their Differential Dynamics, Molecular Mechanisms, and Effects on Tumor Progression
by Kritika Saxena and Mohit Kumar Jolly
Biomolecules 2019, 9(8), 339; https://0-doi-org.brum.beds.ac.uk/10.3390/biom9080339 - 03 Aug 2019
Cited by 138 | Viewed by 9551
Abstract
Hypoxia has been shown to increase the aggressiveness and severity of tumor progression. Along with chronic and acute hypoxic regions, solid tumors contain regions of cycling hypoxia (also called intermittent hypoxia or IH). Cyclic hypoxia is mimicked in vitro and in vivo by [...] Read more.
Hypoxia has been shown to increase the aggressiveness and severity of tumor progression. Along with chronic and acute hypoxic regions, solid tumors contain regions of cycling hypoxia (also called intermittent hypoxia or IH). Cyclic hypoxia is mimicked in vitro and in vivo by periodic exposure to cycles of hypoxia and reoxygenation (H–R cycles). Compared to chronic hypoxia, cyclic hypoxia has been shown to augment various hallmarks of cancer to a greater extent: angiogenesis, immune evasion, metastasis, survival etc. Cycling hypoxia has also been shown to be the major contributing factor in increasing the risk of cancer in obstructive sleep apnea (OSA) patients. Here, we first compare and contrast the effects of acute, chronic and intermittent hypoxia in terms of molecular pathways activated and the cellular processes affected. We highlight the underlying complexity of these differential effects and emphasize the need to investigate various combinations of factors impacting cellular adaptation to hypoxia: total duration of hypoxia, concentration of oxygen (O2), and the presence of and frequency of H–R cycles. Finally, we summarize the effects of cycling hypoxia on various hallmarks of cancer highlighting their dependence on the abovementioned factors. We conclude with a call for an integrative and rigorous analysis of the effects of varying extents and durations of hypoxia on cells, including tools such as mechanism-based mathematical modelling and microfluidic setups. Full article
(This article belongs to the Special Issue 2019 Feature Papers by Biomolecules’ Editorial Board Members)
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