scholarly journals Macrochirality of Self-Assembled and Co-assembled Supramolecular Structures of a Pair of Enantiomeric Peptides

2021 ◽  
Vol 8 ◽  
Author(s):  
Zhen Guo ◽  
Yongshun Song ◽  
Yujiao Wang ◽  
Tingyuan Tan ◽  
Yuwen Ji ◽  
...  
Keyword(s):  
Amino Acids ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Md Simulations ◽  
Supramolecular Structures ◽  
Molecular Chirality ◽  
Left Handed ◽  
Self Assembled ◽  
Shed Light ◽  
Good Agreement

Although macrochirality of peptides’ supramolecular structures has been found to play important roles in biological activities, how macrochirality is determined by the molecular chirality of the constituted amino acids is still unclear. Here, two chiral peptides, Ac-LKLHLHLQLKLLLVLFLFLALK-NH2 (KK-11) and Ac-DKDHDHDQDKDL DVDFDFDADK-NH2 (KKd-11), which were composed entirely of either L- or D-amino acids, were designed for studying the chiral characteristics of the supramolecular microstructures. It was found that monocomponent KK-11 or KKd-11 self-assembled into right- or left-handed helical nanofibrils, respectively. However, when they co-assembled with concentration ratios varied from 1:9 to 9:1, achiral nanowire-like structures were formed. Both circular dichroism and Fourier transform infrared spectra indicated that the secondary structures changed when the peptides co-assembled. MD simulations indicated that KK-11 or KKd-11 exhibited a strong propensity to self-assemble into right-handed or left-handed nanofibrils, respectively. However, when KK-11 and KKd-11 were both presented in a solution, they had a higher probability to co-assemble instead of self-sort. MD simulations indicated that, in their mixtures, they formed nanowires without handedness feature, a good agreement with experimental observation. Our results shed light on the molecular mechanisms of the macrochirality of peptide supramolecular microstructures.

scholarly journals Hydroxytyrosol Decreases LPS- and α-Synuclein-Induced Microglial Activation In Vitro

Antioxidants ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 36 ◽  
Author(s):  
Marta Gallardo-Fernández ◽  
Ruth Hornedo-Ortega ◽  
Isabel M. Alonso-Bellido ◽  
José A. Rodríguez-Gómez ◽  
Ana M. Troncoso ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Biological Activities ◽  
Virgin Olive Oil ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Extra Virgin Olive Oil ◽  
Mitogen Activated Protein ◽  
Anti Inflammatory ◽  
The Relationship ◽  
Shed Light

Neuroinflammation is a common feature shared by neurodegenerative disorders, such as Parkinson’s disease (PD), and seems to play a key role in their development and progression. Microglia cells, the principal orchestrators of neuroinflammation, can be polarized in different phenotypes, which means they are able to have anti-inflammatory, pro-inflammatory, or neurodegenerative effects. Increasing evidence supports that the traditional Mediterranean dietary pattern is related to the reduction of cognitive decline in neurodegenerative diseases. A considerable intake of plant foods, fish, and extra virgin olive oil (EVOO), as well as a moderate consumption of red wine, all characteristic of the Mediterranean diet (MD), are behind these effects. These foods are especially rich in polyphenols, being the most relevant in the MD hydroxytyrosol (HT) and their derivatives present in EVOO, which have demonstrated a wide array of biological activities. Here, we demonstrate that HT is able to reduce the inflammation induced by two different stimuli: lipopolysaccharide and α-synuclein. We also study the possible molecular mechanisms involved in the anti-inflammatory effect of HT, including the study of nuclear factor kappa B (NF-κB), mitogen-activated protein kinases (MAPKs), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and inflammasome. Our data support the use of HT to prevent the inflammation associated with PD and shed light into the relationship between MD and this neurological disorder.

Marine Natural Products with High Anticancer Activities

2020 ◽  
Vol 27 (8) ◽  
pp. 1243-1307 ◽  
Author(s):  
Dario Matulja ◽  
Karlo Wittine ◽  
Nela Malatesti ◽  
Sylvain Laclef ◽  
Maris Turks ◽  
...  
Keyword(s):  
Natural Products ◽  
Marine Natural Products ◽  
Cancer Biology ◽  
Molecular Mechanisms ◽  
Recent Literature ◽  
Biological Activities ◽  
Anticancer Activities ◽  
Total Syntheses ◽  
Biosynthetic Studies ◽  
Shed Light

This review covers recent literature from 2012-2019 concerning 170 marine natural products and their semisynthetic analogues with strong anticancer biological activities. Reports that shed light on cellular and molecular mechanisms and biological functions of these compounds, thus advancing the understanding in cancer biology are also included. Biosynthetic studies and total syntheses, which have provided access to derivatives and have contributed to the proper structure or stereochemistry elucidation or revision are mentioned. The natural compounds isolated from marine organisms are divided into nine groups, namely: alkaloids, sterols and steroids, glycosides, terpenes and terpenoids, macrolides, polypeptides, quinones, phenols and polyphenols, and miscellaneous products. An emphasis is placed on several drugs originating from marine natural products that have already been marketed or are currently in clinical trials.

Self-Assembly of a Chiral Cubic Three-Connected Net from the High Symmetry Molecules C60 and SnI4

2020 ◽  
Author(s):  
Daniel B. Straus ◽  
Robert J. Cava
Keyword(s):  
Organic Synthesis ◽  
Self Assembly ◽  
Van Der Waals ◽  
Van Der Waals Forces ◽  
High Symmetry ◽  
Molecular Chirality ◽  
Chiral Materials ◽  
Self Assembled ◽  
Chiral Centers

The design of new chiral materials usually requires stereoselective organic synthesis to create molecules with chiral centers. Less commonly, achiral molecules can self-assemble into chiral materials, despite the absence of intrinsic molecular chirality. Here, we demonstrate the assembly of high-symmetry molecules into a chiral van der Waals structure by synthesizing crystals of C<sub>60</sub>(SnI<sub>4</sub>)<sub>2</sub> from icosahedral buckminsterfullerene (C<sub>60</sub>) and tetrahedral SnI4 molecules through spontaneous self-assembly. The SnI<sub>4</sub> tetrahedra template the Sn atoms into a chiral cubic three-connected net of the SrSi<sub>2</sub> type that is held together by van der Waals forces. Our results represent the remarkable emergence of a self-assembled chiral material from two of the most highly symmetric molecules, demonstrating that almost any molecular, nanocrystalline, or engineered precursor can be considered when designing chiral assemblies.

Recent Advances of In-Silico Modeling of Potent Antagonists for the Adenosine Receptors

2019 ◽  
Vol 25 (7) ◽  
pp. 750-773 ◽  
Author(s):  
Pabitra Narayan Samanta ◽  
Supratik Kar ◽  
Jerzy Leszczynski
Keyword(s):  
Drug Targets ◽  
Biological Activities ◽  
Scoring Function ◽  
Md Simulations ◽  
Energy Calculation ◽  
Binding Modes ◽  
Macromolecular Systems ◽  
In Silico Modeling ◽  
Mathematical Algorithms ◽  
The Impact

The rapid advancement of computer architectures and development of mathematical algorithms offer a unique opportunity to leverage the simulation of macromolecular systems at physiologically relevant timescales. Herein, we discuss the impact of diverse structure-based and ligand-based molecular modeling techniques in designing potent and selective antagonists against each adenosine receptor (AR) subtype that constitutes multitude of drug targets. The efficiency and robustness of high-throughput empirical scoring function-based approaches for hit discovery and lead optimization in the AR family are assessed with the help of illustrative examples that have led to nanomolar to sub-micromolar inhibition activities. Recent progress in computer-aided drug discovery through homology modeling, quantitative structure-activity relation, pharmacophore models, and molecular docking coupled with more accurate free energy calculation methods are reported and critically analyzed within the framework of structure-based virtual screening of AR antagonists. Later, the potency and applicability of integrated molecular dynamics (MD) methods are addressed in the context of diligent inspection of intricated AR-antagonist binding processes. MD simulations are exposed to be competent for studying the role of the membrane as well as the receptor flexibility toward the precise evaluation of the biological activities of antagonistbound AR complexes such as ligand binding modes, inhibition affinity, and associated thermodynamic and kinetic parameters.

Ginger and Heart Health: From Mechanisms to Therapeutics

2020 ◽  
Vol 13 ◽  
Author(s):  
Sajad Fakhri ◽  
Jayanta Kumar Patra ◽  
Swagat Kumar Das ◽  
Gitishree Das ◽  
Mohammad Bagher Majnooni ◽  
...  
Keyword(s):  
Side Effects ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Health Benefits ◽  
Herbal Medicines ◽  
Cardiovascular Complications ◽  
National Database ◽  
Heart Health ◽  
Natural Entities ◽  
Cardioprotective Effects

Background: As a major cause of morbidity and mortality, cardiovascular diseases (CVDs) are globally increasing. In spite of recent development in the management of cardiovascular complications, CVDs have remained a medical challenge. Numerous conventional drugs are used to play cardioprotective roles; however, they are associated with several side effects. Considering the rich phytochemistry and fewer side effects of herbal medicines, they have gained particular attention to develop novel herbal drugs with cardioprotective potentials. Amongst natural entities, ginger is an extensively used and well-known functional food and condiment, possessing plentiful bioactivities, like antiinflammatory, antioxidant, and antimicrobial properties in several disorders management. Objective: The current review deliberated phytochemical properties as well as the ginger/ginger constituents' biological activities and health benefits in several diseases, with particular attention to cardiovascular complications. Methods: A comprehensive research was conducted using multiple databases, including Scopus, PubMed, Medline, Web of Science, national database (Irandoc and SID), and related articles in terms of the health benefits and cardioprotective effects of ginger/ginger constituents. These data were collected from inception until August 2019. Results: In recent years, several herbal medicines were used to develop new drugs with more potency and also minor side effects. Amongst natural entities, ginger is an extensively used traditional medicine in several diseases. The crude extract, along with related pungent active constituents, is mostly attributed to heart health. The cardioprotective effects of ginger are contributed to its cardiotonic, antihypertensive, anti-hyperlipidemia, and anti-platelet effects. The signaling pathways and molecular mechanisms of ginger regarding its cardioprotective effects are also clarified. Conclusion: This study revealed the biological activities, health benefits, and cardioprotective properties of ginger/ginger constituents along with related mechanisms of action, which gave new insights to show new avenue in the treatment of CVDs.

A Comprehensive Review on Pharmacology and Toxicology of Bioactive Compounds of Lagerstroemia Speciosa (L.) Pers.

2020 ◽  
Vol 06 ◽  
Author(s):  
Surya Kant Tripathi ◽  
Sunayna Behera ◽  
Munmun Panda ◽  
Gokhan Zengin ◽  
Bijesh K. Biswal
Keyword(s):  
Molecular Mechanisms ◽  
Biological Activities ◽  
Health Benefit ◽  
Biologically Active ◽  
Pharmacological Properties ◽  
Lagerstroemia Speciosa ◽  
Novel Drugs ◽  
Corosolic Acid ◽  
Current Article ◽  
Preclinical And Clinical Studies

Background: Lagerstroemia speciosa (L.) Pers is one of the most valuable plants due to its ornamental and pharmacological relevance. It is known for its anti-diabetic activity with proved potent blood sugar-lowering activity. The anti-diabetic activity is due to presence of its biologically active component corosolic acid. Moreover, L. speciosa and its novel purified compounds are also well-known for its several biological activities with beneficial health benefit on the human being. Objectives: This review provides a summary of pharmacokinetics, toxicity, and pharmacological properties of L. speciosa and its purified phytochemicals which may help researchers for building up new researches in near future. Methods: The current article is prepared by collecting through various online and offline databases. Preliminary source of study and data collection for outlining the review was research articles and reviews that have been already published by many reputed publishers, including Springer, Elsevier, Taylor & Francis imprints, BMC, Willy, The Norwegian Academy of Science and Letters, Environmental health prospective (EHP), and PLOS One. Result: The available studies results suggested that the L. speciosa and its phytochemicals showed antidiabetic, anticancer, anti-inflammatory, antimicrobial, antioxidant, antiviral, anti-obesity, and cardio-protective activities. Pharmacokinetic stud-ies suggested the low bioavailability of its purified compounds. However, nano-encapsulation can improve the bioavaila-bility related issue and effectively potentiate the medicinal properties of its constituents. Conclusion: Considering the worthy pharmacological properties, L. speciosa is considered as a potent source of several novel drugs. Though, still preclinical and clinical studies are needed to reveal the targets, molecular mechanisms, bioavail-ability, and toxicity of its constituents.

scholarly journals On the Use of the Discrete Constant pH Molecular Dynamics to Describe the Conformational Space of Peptides

Polymers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 99
Author(s):  
Cristian Privat ◽  
Sergio Madurga ◽  
Francesc Mas ◽  
Jaime Rubio-Martínez
Keyword(s):  
Molecular Dynamics ◽  
Amino Acids ◽  
Md Simulations ◽  
Point Of View ◽  
Conformational Space ◽  
Conformational Sampling ◽  
Protonation State ◽  
Constant Ph ◽  
Biochemical Systems ◽  
Constant Ph Molecular Dynamics

Solvent pH is an important property that defines the protonation state of the amino acids and, therefore, modulates the interactions and the conformational space of the biochemical systems. Generally, this thermodynamic variable is poorly considered in Molecular Dynamics (MD) simulations. Fortunately, this lack has been overcome by means of the Constant pH Molecular Dynamics (CPHMD) methods in the recent decades. Several studies have reported promising results from these approaches that include pH in simulations but focus on the prediction of the effective pKa of the amino acids. In this work, we want to shed some light on the CPHMD method and its implementation in the AMBER suitcase from a conformational point of view. To achieve this goal, we performed CPHMD and conventional MD (CMD) simulations of six protonatable amino acids in a blocked tripeptide structure to compare the conformational sampling and energy distributions of both methods. The results reveal strengths and weaknesses of the CPHMD method in the implementation of AMBER18 version. The change of the protonation state according to the chemical environment is presumably an improvement in the accuracy of the simulations. However, the simulations of the deprotonated forms are not consistent, which is related to an inaccurate assignment of the partial charges of the backbone atoms in the CPHMD residues. Therefore, we recommend the CPHMD methods of AMBER program but pointing out the need to compare structural properties with experimental data to bring reliability to the conformational sampling of the simulations.

scholarly journals Local anesthetics impair the growth and self-renewal of glioblastoma stem cells by inhibiting ZDHHC15-mediated GP130 palmitoylation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xiaoqing Fan ◽  
Haoran Yang ◽  
Chenggang Zhao ◽  
Lizhu Hu ◽  
Delong Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Western Blot ◽  
Local Anesthetics ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Xenograft Model ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Self Renewal

Abstract Background A large number of preclinical studies have shown that local anesthetics have a direct inhibitory effect on tumor biological activities, including cell survival, proliferation, migration, and invasion. There are few studies on the role of local anesthetics in cancer stem cells. This study aimed to determine the possible role of local anesthetics in glioblastoma stem cell (GSC) self-renewal and the underlying molecular mechanisms. Methods The effects of local anesthetics in GSCs were investigated through in vitro and in vivo assays (i.e., Cell Counting Kit 8, spheroidal formation assay, double immunofluorescence, western blot, and xenograft model). The acyl-biotin exchange method (ABE) assay was identified proteins that are S-acylated by zinc finger Asp-His-His-Cys-type palmitoyltransferase 15 (ZDHHC15). Western blot, co-immunoprecipitation, and liquid chromatograph mass spectrometer-mass spectrometry assays were used to explore the mechanisms of ZDHHC15 in effects of local anesthetics in GSCs. Results In this study, we identified a novel mechanism through which local anesthetics can damage the malignant phenotype of glioma. We found that local anesthetics prilocaine, lidocaine, procaine, and ropivacaine can impair the survival and self-renewal of GSCs, especially the classic glioblastoma subtype. These findings suggest that local anesthetics may weaken ZDHHC15 transcripts and decrease GP130 palmitoylation levels and membrane localization, thus inhibiting the activation of IL-6/STAT3 signaling. Conclusions In conclusion, our work emphasizes that ZDHHC15 is a candidate therapeutic target, and local anesthetics are potential therapeutic options for glioblastoma.

scholarly journals RNAseq Reveals Differential Gene Expression Contributing to Phytophthora nicotianae Adaptation to Partial Resistance in Tobacco

Agronomy ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 656
Author(s):  
Jing Jin ◽  
Rui Shi ◽  
Ramsey Steven Lewis ◽  
Howard David Shew
Keyword(s):  
Partial Resistance ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Effective Means ◽  
Phytophthora Nicotianae ◽  
Economic Losses ◽  
Black Shank ◽  
Differential Gene ◽  
Go Terms

Phytophthora nicotianae is a devastating oomycete plant pathogen with a wide host range. On tobacco, it causes black shank, a disease that can result in severe economic losses. Deployment of host resistance is one of the most effective means of controlling tobacco black shank, but adaptation to complete and partial resistance by P. nicotianae can limit the long-term effectiveness of the resistance. The molecular basis of adaptation to partial resistance is largely unknown. RNAseq was performed on two isolates of P. nicotianae (adapted to either the susceptible tobacco genotype Hicks or the partially resistant genotype K 326 Wz/Wz) to identify differentially expressed genes (DEGs) during their pathogenic interactions with K 326 Wz/Wz and Hicks. Approximately 69% of the up-regulated DEGs were associated with pathogenicity in the K 326 Wz/Wz-adapted isolate when sampled following infection of its adapted host K 326 Wz/Wz. Thirty-one percent of the up-regulated DEGs were associated with pathogenicity in the Hicks-adapted isolate on K 326 Wz/Wz. A broad spectrum of over-represented gene ontology (GO) terms were assigned to down-regulated genes in the Hicks-adapted isolate. In the host, a series of GO terms involved in nuclear biosynthesis processes were assigned to the down-regulated genes in K 326 Wz/Wz inoculated with K 326 Wz/Wz-adapted isolate. This study enhances our understanding of the molecular mechanisms of P. nicotianae adaptation to partial resistance in tobacco by elucidating how the pathogen recruits pathogenicity-associated genes that impact host biological activities.

scholarly journals Herb-target virtual screening and network pharmacology for prediction of molecular mechanism of Danggui Beimu Kushen Wan for prostate cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hong Li ◽  
Andrew Hung ◽  
Angela Wei Hong Yang
Keyword(s):  
Prostate Cancer ◽  
Binding Affinity ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Tight Binding ◽  
Experimental Studies ◽  
Network Pharmacology ◽  
High Morbidity ◽  
High Binding ◽  
High Binding Affinity

AbstractProstate cancer (PCa) is a cancer that occurs in the prostate with high morbidity and mortality. Danggui Beimu Kushen Wan (DBKW) is a classic formula for patients with difficult urination including PCa. This study aimed to investigate the molecular mechanisms of DBKW for PCa. We obtained DBKW compounds from our previous reviews. We identified potential targets for PCa from literature search, currently approved drugs and Open Targets database and filtered them by protein–protein interaction network analysis. We selected 26 targets to predict three cancer-related pathways. A total of 621 compounds were screened via molecular docking using PyRx and AutoDock Vina against 21 targets for PCa, producing 13041 docking results. The binding patterns and positions showed that a relatively small number of tight-binding compounds from DBKW were predicted to interact strongly and selectively with three targets. The top five high-binding-affinity compounds were selected to generate a network, indicating that compounds from all three herbs had high binding affinity against the 21 targets and may have potential biological activities with the targets. DBKW contains multi-targeting agents that could act on more than one pathway of PCa simultaneously. Further studies could focus on validating the computational results via experimental studies.

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