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Molecules (Basel, Switzerland) Aug 2014Allicin (diallylthiosulfinate) is a defence molecule from garlic (Allium sativum L.) with a broad range of biological activities. Allicin is produced upon tissue damage... (Review)
Review
Allicin (diallylthiosulfinate) is a defence molecule from garlic (Allium sativum L.) with a broad range of biological activities. Allicin is produced upon tissue damage from the non-proteinogenic amino acid alliin (S-allylcysteine sulfoxide) in a reaction that is catalyzed by the enzyme alliinase. Current understanding of the allicin biosynthetic pathway will be presented in this review. Being a thiosulfinate, allicin is a reactive sulfur species (RSS) and undergoes a redox-reaction with thiol groups in glutathione and proteins that is thought to be essential for its biological activity. Allicin is physiologically active in microbial, plant and mammalian cells. In a dose-dependent manner allicin can inhibit the proliferation of both bacteria and fungi or kill cells outright, including antibiotic-resistant strains like methicillin-resistant Staphylococcus aureus (MRSA). Furthermore, in mammalian cell lines, including cancer cells, allicin induces cell-death and inhibits cell proliferation. In plants allicin inhibits seed germination and attenuates root-development. The majority of allicin's effects are believed to be mediated via redox-dependent mechanisms. In sub-lethal concentrations, allicin has a variety of health-promoting properties, for example cholesterol- and blood pressure-lowering effects that are advantageous for the cardio-vascular system. Clearly, allicin has wide-ranging and interesting applications in medicine and (green) agriculture, hence the detailed discussion of its enormous potential in this review. Taken together, allicin is a fascinating biologically active compound whose properties are a direct consequence of the molecule's chemistry.
Topics: Animals; Anti-Infective Agents; Antineoplastic Agents, Phytogenic; Apoptosis; Arabidopsis; Disulfides; Germination; Humans; Oxidation-Reduction; Plant Roots; Sulfinic Acids
PubMed: 25153873
DOI: 10.3390/molecules190812591 -
Methods in Molecular Biology (Clifton,... 2019The GST pull-down assay is an intuitive and fast in vitro method for analyzing protein-protein or protein-ligand interactions and is comprised of a "bait" which is a...
The GST pull-down assay is an intuitive and fast in vitro method for analyzing protein-protein or protein-ligand interactions and is comprised of a "bait" which is a GST-fused protein expressed in E. coli host or a baculovirus expression system and a "prey" which comprises putative binding partner protein(s) or other ligand molecule(s). This method is suitable for examining the direct interaction between two purified proteins and estimating the extent of the affinity.
Topics: Biological Assay; Carrier Proteins; Humans; Multiprotein Complexes; Protein Binding; Protein Interaction Mapping; Recombinant Fusion Proteins
PubMed: 30565140
DOI: 10.1007/978-1-4939-8910-2_20 -
Advances in Experimental Medicine and... 2016Interleukin-6 (IL-6) is a prototypical cytokine with functional pleiotropy and plays an important role in host defense. When infections or tissue injuries occur, IL-6 is... (Review)
Review
Interleukin-6 (IL-6) is a prototypical cytokine with functional pleiotropy and plays an important role in host defense. When infections or tissue injuries occur, IL-6 is promptly produced by monocytes and macrophages and contributes to removal of infectious agents and restoration of damaged tissues through activation of immune, hematological, and acute-phase responses. Once stress is removed from the host, IL-6 synthesis ends, but uncontrolled excessive or persistent IL-6 production plays a pathological role in the development of various inflammatory diseases and cancers, indicating that IL-6 is a double-edged sword for the host. Thus, the proper IL-6 expression is very important for host defense and is strictly controlled by chromatin structure, transcriptional regulation, and posttranscriptional modification. Differentiation status of cells, various transcription factors, RNA-binding proteins, and microRNAs are involved in this process. Since it is assumed that dysregulation of any of these regulatory molecules may cause abnormal IL-6 expression in a particular disease, further elucidation of the factors and processes involved in IL-6 expression can be expected to facilitate to clarification of pathogenesis and to identification of novel target molecule(s) for specific diseases.
Topics: Animals; Disease; Gene Expression Regulation; Humans; Immune System; Inflammation; Interleukin-6; Protein Processing, Post-Translational; RNA Interference
PubMed: 27734409
DOI: 10.1007/978-94-024-0921-5_4 -
Annual Review of Microbiology Sep 2016The ability of bacteria to recognize kin provides a means to form social groups. In turn these groups can lead to cooperative behaviors that surpass the ability of the... (Review)
Review
The ability of bacteria to recognize kin provides a means to form social groups. In turn these groups can lead to cooperative behaviors that surpass the ability of the individual. Kin recognition involves specific biochemical interactions between a receptor(s) and an identification molecule(s). Recognition specificity, ensuring that nonkin are excluded and kin are included, is critical and depends on the number of loci and polymorphisms involved. After recognition and biochemical perception, the common ensuing cooperative behaviors include biofilm formation, quorum responses, development, and swarming motility. Although kin recognition is a fundamental mechanism through which cells might interact, microbiologists are only beginning to explore the topic. This review considers both molecular and theoretical aspects of bacterial kin recognition. Consideration is also given to bacterial diversity, genetic relatedness, kin selection theory, and mechanisms of recognition.
Topics: Bacteria; Bacterial Physiological Phenomena; Bacterial Proteins; Gene Expression Regulation, Bacterial
PubMed: 27359217
DOI: 10.1146/annurev-micro-102215-095325 -
Journal of Biochemistry Apr 2015Membrane-associated guanylate kinase with an inverted arrangement of protein-protein interaction domains (MAGI)2 (also called synaptic scaffolding molecule (S-SCAM),... (Review)
Review
Membrane-associated guanylate kinase with an inverted arrangement of protein-protein interaction domains (MAGI)2 (also called synaptic scaffolding molecule (S-SCAM), atrophin-1-interacting protein 1, activin receptor-interacting protein 1) is a scaffold protein that binds a wide variety of receptors, cell adhesion molecules and signalling molecules. It also interacts with other scaffold proteins and adaptors, and forms a protein network that supports cell junctions. As it is highly expressed in brain, the study on its roles in synaptic organization initially preceded. However, mounting evidence indicates that MAGI2/S-SCAM functions as a tumour suppressor and plays essential roles to maintain the integrity of cell structures in non-neuronal tissues. We review the articles regarding to MAGI2/S-SCAM outside brain and discuss future perspectives for the research of MAGI family proteins.
Topics: Adaptor Proteins, Signal Transducing; Animals; Brain Neoplasms; Carrier Proteins; Guanylate Kinases; Humans; Models, Biological; Signal Transduction; Tumor Suppressor Proteins
PubMed: 25637633
DOI: 10.1093/jb/mvv009 -
Trends in Immunology Jul 2020How innate immunity gave rise to adaptive immunity in vertebrates remains unknown. We propose an evolutionary scenario beginning with pathogen-associated molecular... (Review)
Review
How innate immunity gave rise to adaptive immunity in vertebrates remains unknown. We propose an evolutionary scenario beginning with pathogen-associated molecular pattern(s) (PAMPs) being presented by molecule(s) on one cell to specific receptor(s) on other cells, much like MHC molecules and T cell receptors (TCRs). In this model, mutations in MHC-like molecule(s) that bound new PAMP(s) would not be recognized by original TCR-like molecule(s), and new MHC-like gene(s) would be lost by neutral drift. Integrating recombination activating gene (RAG) transposon(s) in a TCR-like gene would result in greater recognition diversity, with new MHC-like variants recognized and selected, along with a new RAG/TCR-like system. MHC genes would be selected to present many peptides, through multigene families, allelic polymorphism, and peptide-binding promiscuity.
Topics: Adaptive Immunity; Animals; DNA Transposable Elements; Evolution, Molecular; Genes, RAG-1; Immunity, Innate; Major Histocompatibility Complex; Receptors, Antigen, T-Cell
PubMed: 32467030
DOI: 10.1016/j.it.2020.05.002 -
International Journal of Nanomedicine 2022Bioavailability is an eternal topic that cannot be circumvented by peroral drug delivery. Adequate blood drug exposure after oral administration is a prerequisite for... (Review)
Review
Bioavailability is an eternal topic that cannot be circumvented by peroral drug delivery. Adequate blood drug exposure after oral administration is a prerequisite for effective treatment. Nanovesicles as pleiotropic oral vehicles can solubilize, encapsulate, stabilize an active ingredient and promote the payload absorption via various mechanisms. Vesicular systems with nanoscale size, such as liposomes, niosomes and polymersomes, provide a versatile platform for oral delivery of drugs with distinct nature. The amphiphilicity of vesicles in structure allows hydrophilic and lipophilic molecule(s) either or both to be loaded, being encapsulated in the aqueous cavity or the inner core, respectively. Depending on high oral transport efficiency based on their structural flexibility, gastrointestinal stability, biocompatibility, and/or intestinal epithelial affinity, nanovesicles can markedly augment the oral bioavailability of various poorly absorbed drugs. Vesicular drug delivery systems (VDDSs) demonstrate a lot of preferences and are becoming more prominent of late years in biomedical applications. Equally, these systems can potentiate a drug's therapeutic index by ameliorating the oral absorption. This review devotes to comment on various VDDSs with special emphasis on the peroral drug delivery. The classification of nanovesicles, preparative processes, intestinal transport mechanisms, in vivo fate, and design rationale were expounded. Knowledge on vesicles-mediated oral drug delivery for bioavailability enhancement has been properly provided. It can be concluded that VDDSs with many merits will step into an energetic arena in oral drug delivery.
Topics: Biological Availability; Liposomes; Administration, Oral; Hydrophobic and Hydrophilic Interactions; Excipients
PubMed: 36262189
DOI: 10.2147/IJN.S382192 -
Methods in Molecular Biology (Clifton,... 2020Estimating the range of three-dimensional structures (conformations) that are available to a molecule is a key component of computer-aided drug design. Quantum... (Review)
Review
Estimating the range of three-dimensional structures (conformations) that are available to a molecule is a key component of computer-aided drug design. Quantum mechanical simulation offers improved accuracy over forcefield methods, but at a high computational cost. The question is whether this increased cost can be justified in a context in which high-throughput analysis of large numbers of molecules is often key. This chapter discusses the application of quantum mechanics to conformational searching, with a focus on three key challenges: (1) the generation of ensembles that include a good approximation to a molecule's bioactive conformation at as prominent a ranking as possible; (2) rational analysis and modification of a pre-established bioactive conformation in terms of its energetics; and (3) approximation of real solution-phase conformational ensembles in tandem with NMR data. The impact of QM on the high-throughput application (1) is debatable, meaning that for the moment its primary application is still lower-throughput applications such as (2) and (3). The optimal choice of QM method is also discussed. Rigorous benchmarking suggests that DFT methods are only acceptable when used with large basis sets, but a trickle of papers continue to obtain useful results with relatively low-cost methods, leading to a dilemma that the literature has yet to fully resolve.
Topics: Computer Simulation; Drug Design; Drug Discovery; Molecular Conformation; Pharmaceutical Preparations; Quantum Theory; Software
PubMed: 32016896
DOI: 10.1007/978-1-0716-0282-9_14 -
Frontiers in Chemistry 2023Supramolecular containers have long been applied to regulate organic reactions with distinct selectivity, owing to their diverse functions such as the ability to pose a... (Review)
Review
Supramolecular containers have long been applied to regulate organic reactions with distinct selectivity, owing to their diverse functions such as the ability to pose a guest molecule(s) with a certain orientation and conformation. In this review, we try to illustrate how self-assembled coordination cages could achieve this goal. Two representative cage hosts, namely, self-assembled Pd(II)-ligand octahedral coordination cages ([PdL]) and self-assembled Ga(III)-ligand tetrahedral coordination cages ([GaL]) are selected as the pilot hosts that this mini review covers. Representative works in this area are presented here in brief.
PubMed: 37731456
DOI: 10.3389/fchem.2023.1269471 -
Pharmacology Research & Perspectives Dec 2019Paul Ehrlich's concept of the magic bullet, by which a induces pharmacological effects by interacting with a has been a strong driving force in pharmacology for a... (Review)
Review
Paul Ehrlich's concept of the magic bullet, by which a induces pharmacological effects by interacting with a has been a strong driving force in pharmacology for a century. It is continually thwarted, though, by the fact that the treated organism is highly dynamic and the target molecule(s) is (are) never static. In this article, we address some of the factors that modify and cause the mobility and plasticity of drug targets and their interactions with ligands and discuss how these can lead to unexpected (lack of) effects of drugs. These factors include genetic, epigenetic, and phenotypic variability, cellular plasticity, chronobiological rhythms, time, age and disease resolution, sex, drug metabolism, and distribution. We emphasize four existing approaches that can be taken, either singly or in combination, to try to minimize effects of pharmacological plasticity. These are firstly, to enhance specificity using target conditions close to those in diseases, secondly, by simultaneously or thirdly, sequentially aiming at multiple targets, and fourthly, in synchronization with concurrent dietary, psychological, training, and biorhythm-synchronizing procedures to optimize drug therapy.
Topics: Epigenesis, Genetic; Gene Expression Regulation; Humans; Ligands; Molecular Targeted Therapy; Pharmacology, Clinical
PubMed: 31768257
DOI: 10.1002/prp2.532