Biogenic Molecules Research Articles

Identification of potential focal adhesion kinase (FAK) inhibitors: a molecular modeling approach

Focal adhesion kinase (FAK) is an enzyme of paramount importance as it is involved in several critical roles, which are linked to proliferation of cancer cells. FAK is quintessential for cancer cell mitigation, adhesion and survival, downregulation of which interferes with the growth of cancer cells. The expression of FAK is elevated in breast cancer, hepatocellular carcinomas, neuroblastoma cells, demonstrating the need for FAK inhibitors as a potential treatment. Based on an in silico drug screen, the study aimed to identify potential FAK inhibitors. 3180 molecules retrieved from the Zinc database comprising biogenic molecules, FDA-approved drugs and compounds in clinical trials were screened against the FAK enzyme (PDB:2ETM). The XP docking study of the best 51 ligands revealed that ZINC02033589 (Silymarin) showed good binding to FAK with −10.97 kcal/mol dock score followed by ZINC00518397 with −8.23 kcal/mol and ZINC03831112 − 8.07 kcal/mol. The interactions of the top three ligands with FAK were further validated by molecular dynamic simulation study of 100 ns and MM-GBSA calculations. The ΔG of binding of ZINC02033589, ZINC00518397 and ZINC03831112 was found to be −59.09, −45.08 and −48.53 kcal/mol respectively. The study established the fact that among the three molecules, ZINC02033589 showed good stability and binding towards FAK. These results could usher in the development of potential FAK inhibitor entities, that could be persuaded and substantiated by the molecules identified in this study for subsequent synthetic and bioactivity research studies. Communicated by Ramaswamy H. Sarma

Expression of genes involved in the biosynthesis of bacterial cellulose by symbiotic culture of Medusomyces gisevii, depending on the available carbon source

Scientific and practical interest in the design of symbiotic cultures is determined by their potential for use in biotechnological processes for the production of a wide range of biogenic molecules. We have determined the expression levels of genes involved in the biosynthesis of cellulose by the symbiotic culture Medusomyces gisevii that had been statically grown either on glucose or sucrose or fructose, considered as three most economically justified carbon sources. 16S ribosomal RNA was used as a reference gene. The PCR primers used were bcsA1, bcsA2, bcsA3, bcsA4, bcsB, DGC, PDE, UDP GT. Overall higher gene expression levels were observed when cultivating a symbiotic culture of Medusomyces gisevi on glucose or sucrose substrates compared with fructose. Furthermore, the expression of these genes in the synthesized BC gel films is significantly higher compared to that in the bacterial culture medium.

NO at low concentration can enhance the formation of highly oxygenated biogenic molecules in the atmosphere

The interaction between nitrogen monoxide (NO) and organic peroxy radicals (RO2) greatly impacts the formation of highly oxygenated organic molecules (HOM), the key precursors of secondary organic aerosols. It has been thought that HOM production can be significantly suppressed by NO even at low concentrations. Here, we perform dedicated experiments focusing on HOM formation from monoterpenes at low NO concentrations (0 – 82 pptv). We demonstrate that such low NO can enhance HOM production by modulating the RO2 loss and favoring the formation of alkoxy radicals that can continue to autoxidize through isomerization. These insights suggest that HOM yields from typical boreal forest emissions can vary between 2.5%-6.5%, and HOM formation will not be completely inhibited even at high NO concentrations. Our findings challenge the notion that NO monotonically reduces HOM yields by extending the knowledge of RO2-NO interactions to the low-NO regime. This represents a major advance towards an accurate assessment of HOM budgets, especially in low-NO environments, which prevails in the pre-industrial atmosphere, pristine areas, and the upper boundary layer.

Ice nucleation catalyzed by the photosynthesis enzyme RuBisCO and other abundant biomolecules

Atmospheric aerosol and the cloud droplets and ice crystals that grow on them remain major sources of uncertainty in global climate models. A subset of aerosol, ice nucleating particles, catalyze the freezing of water droplets at temperatures warmer than −38 °C. Here we show that RuBisCO, one of the most abundant proteins in plants and phytoplankton, is one of the most efficient known immersion ice nucleating particles with a mean freezing temperature of −7.9 ± 0.3 °C. Further, we demonstrate RuBisCO is present in ambient continental aerosol where it can serve as an ice nucleating particle. Other biogenic molecules act as immersion ice nucleating particles, in the range of −19 to −26 °C. In addition, our results indicate heat denaturation is not a universal indicator of the proteinaceous origin of ice nucleating particles, suggesting current studies may fail to accurately quantify biological ice nucleating particle concentrations and their global importance.

Chelation of Zinc with Biogenic Amino Acids: Description of Properties Using Balaban Index, Assessment of Biological Activity on Spirostomum Ambiguum Cellular Biosensor, Influence on Biofilms and Direct Antibacterial Action.

The complexation of biogenic molecules with metals is the widespread strategy in screening for new pharmaceuticals with improved therapeutic and physicochemical properties. This paper demonstrates the possibility of using simple QSAR modeling based on topological descriptors for chelates study. The presence of a relationship between the structure (J) and lipophilic properties (logP) of zinc complexes with amino acids, where two molecules coordinate the central atom through carboxyl oxygen and amino group nitrogen, and thus form a double ring structure, was predicted. Using a cellular biosensor model for Gly, Ala, Met, Val, Phe and their complexes Zn(AA)2, we experimentally confirmed the existence of a direct relationship between logP and biological activity (Ea). The results obtained using topological analysis, Spirotox method and microbiological testing allowed us to assume and prove that the chelate complex of zinc with methionine has the highest activity of inhibiting bacterial biofilms, while in aqueous solutions it does not reveal direct antibacterial effect.

Chemistry of difluoromethylene phosphonates: history, state of the art, and prospects

Difluoromethylene phosphonates are non-hydrolyzable bioisosteres of phosphates. They have proven their efficiency as inhibitors of the enzymes that specialize in utilizing these essential biogenic molecules. Difluoromethylene phosphonates show a broad spectrum of biological activity and are used as molecular tools to study enzymes and enzyme-substrate interactions. In this review, we briefly summarize the importance of difluoromethylene phosphonates as a distinct class of synthetic phosphonates resulting from multidisciplinary efforts of the organophosphorus, organofluorine, and bioorganic research communities. We outline the development of the synthetic chemistry of difluoromethylene phosphonates from the historical perspective, discuss the most recent trends in the field, and highlight the existing challenges and unsolved questions

Kinetics of reactions of NH4 + with some biogenic organic molecules and monoterpenes in helium and nitrogen carrier gases: A potential reagent ion for selected ion flow tube mass spectrometry.

To assess the suitability of NH4 + as a reagent ion for trace gas analysis by selected ion flow tube mass spectrometry, SIFT-MS, its ion chemistry must be understood. Thus, rate coefficients and product ions for its reactions with typical biogenic molecules and monoterpenes need to be experimentally determined in both helium, He, and nitrogen, N2 , carrier gases. NH4 + and H3 O+ were generated in a microwave gas discharge through an NH3 and H2 O vapour mixture and, after m/z selection, injected into He and N2 carrier gas. Using the conventional SIFT method, NH4 + reactions were then studied with M, the biogenic molecules acetone, 1-propanol, 2-butenal, trans-2-heptenal, heptanal, 2-heptanone, 2,3-heptanedione and 15 monoterpene isomers to obtain rate coefficients, k, and product ion branching ratios. Polarisabilities and dipole moments of the reactant molecules and the enthalpy changes in proton transfer reactions were calculated using density functional theory. The k values for the reactions of the biogenic molecules were invariably faster in N2 than in He but similar in both bath gases for the monoterpenes. Adducts NH4 + M were the dominant product ions in He and N2 for the biogenic molecules, whereas both MH+ and NH4 + M product ions were observed in the monoterpene reactions; the monoterpene ratio correlating (R2 =0.7) with the proton affinity, PA, of the monoterpene molecule as calculated. The data indicate that this adduct ion formation is the result of bimolecular rather than termolecular association. NH4 + can be a useful reagent ion for SIFT-MS analyses of molecules with PA(M) < PA(NH3 ) when the dominant single product ion is the adduct NH4 + M. For molecules with PA(M) > PA(NH3 ), such as monoterpenes, both MH+ and NH4 + M ions are likely products, which must be determined along with k by experiment.

A Review of Nanotechnology as a Novel Method of Gene Transfer in Plants

Purpose: Nanotechnology has evolved as an effective tool in numerous fields including agriculture, medicine and engineering. Recently it’s potential as an alternative genetic transformation method has been identified. However, a comprehensive understanding over nanoparticles and their behavior in living cells is important to realize the full potential of this technology in biotechnological applications. Therefore, we review the application potential of widely employed nanoparticles in plant transformation here.Literature/Background: Development of new crop varieties with desirable traits via biotechnological applications is a solution for challenges associated with climate change and higher population growth. In such aspects, transformation of plant cells which is known as the process of changing one’s genome by integration exogenous DNA, is an absolute necessity and results far better and improved stable characteristics in original. Rigid and multi layered cell wall impedes penetration of exterior biomolecules and hence causes the transformation process complicated. Even though, numerous conventional methods have been established for plant transformation, lower transformation efficiency, tissue damage and random integration of transgenes warrants the need for novel approaches. In this context, novel techniques have been explored and as a result nanoparticles have been found effective in transformation of protoplasts as well as intact plant cells. Nanoparticles internalized either via endocytosis or direct penetration release transgenes from nanoparticle-DNA complexes and result in transient or stable expression. Nanoparticles ensure higher transformation efficiency, no transgenic silencing and protection of biogenic molecules from degradation by intracellular nucleases.

A History of Molecular Level Analysis of Natural Organic Matter by FTICR Mass Spectrometry and The Paradigm Shift in Organic Geochemistry.

Natural organic matter (NOM) is a complex mixture of biogenic molecules resulting from the deposition and transformation of plant and animal matter. It has long been recognized that NOM plays an important role in many geological, geochemical, and environmental processes. Of particular concern is the fate of NOM in response to a warming climate in environments that have historically sequestered carbon (e.g., peatlands and swamps) but may transition to net carbon emitters. In this review, we will highlight developments in the application of high-field Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) in identifying the individual components of complex NOM mixtures, focusing primarily on the fraction that is dissolved in natural waters (dissolved organic matter or DOM). We will first provide some historical perspective on developments in FTICR technology that made molecular-level characterizations of DOM possible. A variety of applications of the technique will then be described, followed by our view of the future of high-field FTICR MS in carbon cycling research, including a particularly exciting metabolomic approach.

Pharmaceutical Technology Innovation Strategy Based on the Function of Blood Transport Proteins as DDS Carriers for the Treatment of Intractable Disorders and Cancer.

Blood transport proteins are biogenic molecules with unique and interesting inherent characteristics that make up living organisms. As the utilization of their inherent characteristics can be a groundbreaking strategy to resolve and improve several clinical problems, attempts have been made to develop pharmaceutical and biomedical preparations based on blood transport proteins for the treatment and diagnosis of disorders. Among various blood transport proteins, we focus on the immense potential of hemoglobin and albumin to serve as carriers of biomedical gases (oxygen and carbon monoxide) and anticancer agents (low-molecular compounds and antisense oligodeoxynucleotides), respectively, for the development of innovative drug delivery systems (DDS) to treat intractable disorders and solid cancers. In this review, I introduce the pharmaceutical technology, strategies, and application of DDS carriers that have been designed on the basis of the structure and function of hemoglobin and albumin. In addition, the prospect of using hemoglobin and albumin as materials for DDS carriers is discussed.

WITHDRAWN: Can Traditional Chinese Medicine provide insights into controlling the COVID-19 pandemic: Serpentinization-induced lithospheric long-wavelength magnetic anomalies in Proterozoic bedrocks in a weakened geomagnetic field mediate the aberrant transformation of biogenic molecules in COVID-19 via magnetic catalysis

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Metabolite Structure Assignment Using In Silico NMR Techniques.

A major challenge for metabolomic analysis is to obtain an unambiguous identification of the metabolites detected in a sample. Among metabolomics techniques, NMR spectroscopy is a sophisticated, powerful, and generally applicable spectroscopic tool that can be used to ascertain the correct structure of newly isolated biogenic molecules. However, accurate structure prediction using computational NMR techniques depends on how much of the relevant conformational space of a particular compound is considered. It is intrinsically challenging to calculate NMR chemical shifts using high-level DFT when the conformational space of a metabolite is extensive. In this work, we developed NMR chemical shift calculation protocols using a machine learning model in conjunction with standard DFT methods. The pipeline encompasses the following steps: (1) conformation generation using a force field (FF)-based method, (2) filtering the FF generated conformations using the ASE-ANI machine learning model, (3) clustering of the optimized conformations based on structural similarity to identify chemically unique conformations, (4) DFT structural optimization of the unique conformations, and (5) DFT NMR chemical shift calculation. This protocol can calculate the NMR chemical shifts of a set of molecules using any available combination of DFT theory, solvent model, and NMR-active nuclei, using both user-selected reference compounds and/or linear regression methods. Our protocol reduces the overall computational time by 2 orders of magnitude over methods that optimize the conformations using fully ab initio methods, while still producing good agreement with experimental observations. The complete protocol is designed in such a manner that makes the computation of chemical shifts tractable for a large number of conformationally flexible metabolites.

The Cytotoxic and Apoptotic Effects of the Brown Algae Colpomenia sinuosa are Mediated by the Generation of Reactive Oxygen Species.

Brown algae are a novel resource of biogenic molecules, however few studies have been conducted in the Mediterranean to assess the cytotoxic mechanisms of algal-derived compounds. This study focuses on the antineoplastic activity of extracts from non-investigated algae of the Lebanese coast, Colpomenia sinuosa. Extracts’ antineoplastic activities were evaluated by MTT and trypan blue on different tumorigenic cells. Results indicated that the most potent extract was obtained by soxhlet using dichloromethane:methanol solvent (DM soxhlet) against HCT-116. Wound healing assay confirmed that this extract decreased the migration potential of HCT-116 cells with minimal effects on non-tumorigenic cells. It also induced an increase in the subG1 population as determined by flow cytometry. Western blot analysis demonstrated that apoptosis in treated HCT-116 cells was induced via upregulation of p21 protein and downregulation of the anti-apoptotic Bcl 2, which led to caspases activation. The latter, catalyzes the degradation of PARP-1, and thus suppresses cancer proliferation. Morphological alterations, further confirmed apoptosis. A strong pro-oxidant activity evidenced by the enhanced generation of reactive oxygen species (ROS) was observed in HCT-116 treated cells. Interestingly, a strong antioxidant effectively blocked effect induced by the extract. These results indicate that C. sinuosa is a source of bioactive compounds possessing pro-apoptotic and anti-migratory efficacy.

Discovery of the oldest known biomarkers provides evidence for phototrophic bacteria in the 1.73Ga Wollogorang Formation, Australia.

The discovery of mid-Proterozoic (1.8-0.8 billion years ago, Ga) indigenous biomarkers is a challenge, since biologically informative molecules of such antiquity are commonly destroyed by metamorphism or overprinted by drilling fluids and other anthropogenic petroleum products. Previously, the oldest clearly indigenous biomarkers were reported from the 1.64Ga Barney Creek Formation in the northern Australian McArthur Basin. In this study, we present the discovery of biomarker molecules from carbonaceous shales of the 1.73Ga Wollogorang Formation in the southern McArthur Basin, extending the biomarker record back in time by ~90 million years. The extracted hydrocarbons illustrate typical mid-Proterozoic signatures with a large unresolved complex mixture, high methyl alkane/n-alkane ratios and the absence of eukaryotic steranes. Acyclic isoprenoids, saturated carotenoid derivatives, bacterial hopanes and aromatic hopanoids and steroids also were below detection limits. However, continuous homologous series of low molecular weight C14 -C19 2,3,4- and 2,3,6-trimethyl aryl isoprenoids (AI) were identified, and C20 -C22 AI homologues were tentatively identified. Based on elevated abundances relative to abiogenic isomers, we interpret the 2,3,6-AI isomer series as biogenic molecules and the 2,3,4-AI series as possibly biogenic. The biological sources for the 2,3,6-AI series include carotenoids of cyanobacteria and/or green sulphur bacteria (Chlorobiaceae). The lower concentrated 2,3,4-AI series may be derived from purple sulphur bacteria (Chromatiaceae). These degradation products of carotenoids are the oldest known clearly indigenous molecules of likely biogenic origin.

Current Development of siRNA Bioconjugates: From Research to the Clinic.

Small interfering RNAs (siRNAs) acting via RNA interference mechanisms are able to recognize a homologous mRNA sequence in the cell and induce its degradation. The main problems in the development of siRNA-based drugs for therapeutic use are the low efficiency of siRNA delivery to target cells and the degradation of siRNAs by nucleases in biological fluids. Various approaches have been proposed to solve the problem of siRNA delivery in vivo (e.g., viruses, cationic lipids, polymers, nanoparticles), but all have limitations for therapeutic use. One of the most promising approaches to solve the problem of siRNA delivery to target cells is bioconjugation; i.e., the covalent connection of siRNAs with biogenic molecules (lipophilic molecules, antibodies, aptamers, ligands, peptides, or polymers). Bioconjugates are “ideal nanoparticles” since they do not need a positive charge to form complexes, are less toxic, and are less effectively recognized by components of the immune system because of their small size. This review is focused on strategies and principles for constructing siRNA bioconjugates for in vivo use.

Conjoined-network rendered stiff and tough hydrogels from biogenic molecules.

Hydrogels from biological sources are expected as potential structural biomaterials, but most of them are either soft or fragile. Here, a new strategy was developed to construct hydrogels that were both stiff and tough via the formation of the conjoined-network, which was distinct from improving homogeneity or incorporating energy dissipation mechanisms (double-network) approaches. Conjoined-network hydrogels stand for a class of hydrogels consisting of two or more networks that are connected by sharing interconnection points to collaborate and featured as follows: (i) All the composed networks had a similar or equal energy dissipation mechanism, and (ii) these networks were intertwined to effectively distribute stress in the whole system. As a specific example, a biogenic conjoined-network hydrogel was prepared by electrostatically cross-linking the chitosan-gelatin composite with multivalent sodium phytate. The combination of high compressive modulus and toughness was realized at the same time in the chitosan-gelatin-phytate system. Moreover, these physical hydrogels exhibited extraordinary self-recovery and fatigue resistance ability. Our results provide a general strategy for the design of biocompatible stiff and tough conjoined-network hydrogels due to a variety of potential cross-linking mechanisms available (e.g., electrostatic attraction, host-guest interaction, and hydrogen bonding).

Marine biogenics in sea spray aerosols interact with the mTOR signaling pathway

Sea spray aerosols (SSAs) have profound effects on our climate and ecosystems. They also contain microbiota and biogenic molecules which could affect human health. Yet the exposure and effects of SSAs on human health remain poorly studied. Here, we exposed human lung cancer cells to extracts of a natural sea spray aerosol collected at the seashore in Belgium, a laboratory-generated SSA, the marine algal toxin homoyessotoxin and a chemical inhibitor of the mammalian target of rapamycin (mTOR) pathway. We observed significant increased expression of genes related to the mTOR pathway and Proprotein convertase subtilisin/kexin type 9 (PCSK9) after exposure to homoyessotoxin and the laboratory-generated SSA. In contrast, we observed a significant decrease in gene expression in the mTOR pathway and of PCSK9 after exposure to the natural SSA and the mTOR inhibitor, suggesting induction of apoptosis. Our results indicate that marine biogenics in SSAs interact with PCSK9 and the mTOR pathway and can be used in new potential pharmaceutical applications. Overall, our results provide a substantial molecular evidence base for potential beneficial health effects at environmentally relevant concentrations of natural SSAs.

Bioactive potential analysis of brown seaweed Sargassum wightii using UV-VIS and FT-IR

The current study was investigated to explore the biogenic molecules of Sargassum wightii collected from the south east of Tamil Nadu, India. The biogenic molecules extracted from Sargassum wightii by using methanol as a solvent and the analysis was carried out by using UV-Visible spectroscopy and FT-IR. The UV-Visible spectrum of the methanolic extract of Sargassum wightii exposed the existence of the biogenic molecules separated from 200 - 1100 nm among the absorption. The incidence of peaks from 234-676 nm discovered the presence of flavonoids and its derivatives. The unprocessed methanolic extract of Sargassum wightii was travelled in to FT-IR and it indicated the being of phenols and flavonoids their functional groups such as alcohol, alkane, carboxylic acids, esters, ethers, alkynes and aromatics. From the results, the future aim of this study is necessary to develop the target site to treat dreadful diseases.&#x0D; Keywords: Sargassum Wightii, FT-IR, UV-Visible Spectroscopy, Phytochemical analysis.

Optical, electrochemical and catalytic methods for in-vitro diagnosis using carbonaceous nanoparticles: a review.

This review (with 261 refs.) summarizes the progress that has been made in the field of in-vitro diagnosis using carbonaceous nanoparticles (CNPs). Signal readout is mostly based on fluorometry, electrochemistry and colorimetry. Following an introduction, the next two sections cover methods for the fabrication and separation of CNPs. This is followed by sections on (a) fluorometric methods, (b) electrochemical methods, and (c) colorimetric methods for detecting various analytes. Several subsections discuss detection schemes for analytes such as metal ions, pH value, reactive oxygen species, small biogenic molecules (for example glucose, ascorbic acid, amino acids, dopamine), and biomacromolecules (such as enzymes, cancer markers, DNA). A further section discusses methods based on the peroxidase-like activity of CNPs, and how they can be employed for the determination of species such as glucose, cholesterol, glutathione, anduric acid via H2O2-based chromogenic methods. Finally, the challenges and future perspectives in this research area are discussed. Graphical abstract A review is presented on the progress that has been made in recent years in sensing platforms for in-vitro diagnosis usingcarbonaceous nanoparticles (CNPs). Signal readout is mostly based on fluorometry, electrochemistry and colorimetry, respectively. Besides, the fabrication and separation strategies of CNPs are also demonstrated.

Modification of Extracellular Vesicles by Fusion with Liposomes for the Design of Personalized Biogenic Drug Delivery Systems.

Extracellular vesicles (EVs) are recognized as nature's own carriers to transport macromolecules throughout the body. Hijacking this endogenous communication system represents an attractive strategy for advanced drug delivery. However, efficient and reproducible loading of EVs with therapeutic or imaging agents still represents a bottleneck for their use as a drug delivery system. Here, we developed a method for modifying cell-derived EVs through their fusion with liposomes containing both membrane and soluble cargoes. The fusion of EVs with functionalized liposomes was triggered by polyethylene glycol (PEG) to create smart biosynthetic hybrid vectors. This versatile method proved to be efficient to enrich EVs with exogenous lipophilic or hydrophilic compounds, while preserving their intrinsic content and biological properties. Hybrid EVs improved cellular delivery efficiency of a chemotherapeutic compound by a factor of 3-4, as compared to the free drug or the drug-loaded liposome precursor. On one side, this method allows the biocamouflage of liposomes by enriching their lipid bilayer and inner compartment with biogenic molecules. On the other side, the proposed fusion strategy enables efficient EV loading, and the pharmaceutical development of EVs with adaptable activity and drug delivery property.