-
Nano-micro Letters Sep 2023Chirality, as the symmetric breaking of molecules, plays an essential role in physical, chemical and especially biological processes, which highlights the accurate...
Chirality, as the symmetric breaking of molecules, plays an essential role in physical, chemical and especially biological processes, which highlights the accurate distinction among heterochiralities as well as the precise preparation for homochirality. To this end, the well-designed structure-specific recognizer and catalysis reactor are necessitated, respectively. However, each kind of target molecules requires a custom-made chiral partner and the dynamic disorder of spatial-orientation distribution of molecules at the ensemble level leads to an inefficient protocol. In this perspective article, we developed a universal strategy capable of realizing the chirality detection and control by the external symmetry breaking based on the alignment of the molecular frame to external stimuli. Specifically, in combination with the discussion about the relationship among the chirality (molecule), spin (electron) and polarization (photon), i.e., the three natural symmetry breaking, single-molecule junctions were proposed to achieve a single-molecule/event-resolved detection and synthesis. The fixation of the molecular orientation and the CMOS-compatibility provide an efficient interface to achieve the external input of symmetry breaking. This perspective is believed to offer more efficient applications in accurate chirality detection and precise asymmetric synthesis via the close collaboration of chemists, physicists, materials scientists, and engineers.
PubMed: 37698706
DOI: 10.1007/s40820-023-01184-5 -
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 -
Journal of the American Chemical Society Oct 2023Reactions capable of transposing the oxidation levels of adjacent carbon atoms enable rapid and fundamental alteration of a molecule's reactivity. Herein, we report the...
Reactions capable of transposing the oxidation levels of adjacent carbon atoms enable rapid and fundamental alteration of a molecule's reactivity. Herein, we report the 1,2-transposition of the carbon atom oxidation level in cyclic and acyclic tertiary amides, resulting in the one-pot synthesis of 1,2- and 1,3-oxygenated tertiary amines. This oxidation level transfer was facilitated by the careful orchestration of an iridium-catalyzed reduction with the functionalization of transiently formed enamine intermediates. A novel 1,2-carbonyl transposition is described, and the breadth of this redox transposition strategy has been further explored by the development of aminoalcohol and enaminone syntheses. The diverse β-functionalized amine products were shown to be multifaceted and valuable synthetic intermediates, accessing challenging biologically relevant motifs.
PubMed: 37756523
DOI: 10.1021/jacs.3c08466 -
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 -
Chemical Society Reviews Mar 2021Recent advances in our understanding of RNA biology have uncovered crucial roles for RNA in multiple disease states, ranging from viral and bacterial infections to... (Review)
Review
Recent advances in our understanding of RNA biology have uncovered crucial roles for RNA in multiple disease states, ranging from viral and bacterial infections to cancer and neurological disorders. As a result, multiple laboratories have become interested in developing drug-like small molecules to target RNA. However, this development comes with multiple unique challenges. For example, RNA is inherently dynamic and has limited chemical diversity. In addition, promiscuous RNA-binding ligands are often identified during screening campaigns. This Tutorial Review overviews important considerations and advancements for generating RNA-targeted small molecules, ranging from fundamental chemistry to promising small molecule examples with demonstrated clinical efficacy. Specifically, we begin by exploring RNA functional classes, structural hierarchy, and dynamics. We then discuss fundamental RNA recognition principles along with methods for small molecule screening and RNA structure determination. Finally, we review unique challenges and emerging solutions from both the RNA and small molecule perspectives for generating RNA-targeted ligands before highlighting a selection of the "Greatest Hits" to date. These molecules target RNA in a variety of diseases, including cancer, neurodegeneration, and viral infection, in cellular and animal model systems. Additionally, we explore the recently FDA-approved small molecule regulator of RNA splicing, risdiplam, for treatment of spinal muscular atrophy. Together, this Tutorial Review showcases the fundamental role of chemical and molecular recognition principles in enhancing our understanding of RNA biology and contributing to the rapidly growing number of RNA-targeted probes and therapeutics. In particular, we hope this widely accessible review will serve as inspiration for aspiring small molecule and/or RNA researchers.
Topics: Animals; Base Sequence; High-Throughput Screening Assays; Humans; Ligands; Molecular Probes; Neoplasms; Nucleic Acid Conformation; RNA; Small Molecule Libraries; Virus Diseases
PubMed: 33458725
DOI: 10.1039/d0cs01261k -
Frontiers in Plant Science 2022The liaison between Nitric oxide (NO) and phytohormones regulates a myriad of physiological processes at the cellular level. The interaction between NO and phytohormones... (Review)
Review
The liaison between Nitric oxide (NO) and phytohormones regulates a myriad of physiological processes at the cellular level. The interaction between NO and phytohormones is mainly influenced by NO-mediated post-translational modifications (PTMs) under basal as well as induced conditions. Protein S-nitrosylation is the most prominent and widely studied PTM among others. It is the selective but reversible redox-based covalent addition of a NO moiety to the sulfhydryl group of cysteine (Cys) molecule(s) on a target protein to form S-nitrosothiols. This process may involve either direct S-nitrosylation or indirect S-nitrosylation followed by transfer of NO group from one thiol to another (transnitrosylation). During S-nitrosylation, NO can directly target Cys residue (s) of key genes involved in hormone signaling thereby regulating their function. The phytohormones regulated by NO in this manner includes abscisic acid, auxin, gibberellic acid, cytokinin, ethylene, salicylic acid, jasmonic acid, brassinosteroid, and strigolactone during various metabolic and physiological conditions and environmental stress responses. S-nitrosylation of key proteins involved in the phytohormonal network occurs during their synthesis, degradation, or signaling roles depending upon the response required to maintain cellular homeostasis. This review presents the interaction between NO and phytohormones and the role of the canonical NO-mediated post-translational modification particularly, S-nitrosylation of key proteins involved in the phytohormonal networks under biotic and abiotic stresses.
PubMed: 35401598
DOI: 10.3389/fpls.2022.865542 -
Cancer Diagnosis & Prognosis 2023DNA mismatch repair system (MMR) is considered a leading genetic mechanism in stabilizing DNA structure and maintaining its function. DNA MMR is a highly conserved... (Review)
Review
DNA mismatch repair system (MMR) is considered a leading genetic mechanism in stabilizing DNA structure and maintaining its function. DNA MMR is a highly conserved system in bacteria, prokaryotic, and eukaryotic cells, and provides the highest protection to DNA by repairing micro-structural alterations. DNA MMR proteins are involved in the detection and repair of intra-nucleotide base-to-base errors inside the complementary DNA strand recognizing the recently synthesized strand from the parental template. During DNA replication, a spectrum of errors including base insertion, deletion, and miss-incorporation negatively affect the molecule's structure and its functional stability. A broad spectrum of genomic alterations such as promoter hyper methylation, mutation, and loss of heterozygosity (LOH) in MMR genes including predominantly hMLH1, hMSH2, hMSH3, hMSH6, hPMS1, and hPMS2 lead to their loss of base-to-base error repairing procedure. Microsatellite instability (MSI) refers to the DNA MMR gene alterations that are observed in a variety of malignancies of different histological origins. In the current review, we present the role of DNA MMR deficiency in breast adenocarcinoma, a leading cancer-based cause of death in females worldwide.
PubMed: 36875308
DOI: 10.21873/cdp.10197 -
Annals of the New York Academy of... Jul 2020Aberrant RNA structure and function operate in neurological disease progression and severity. As RNA contributes to disease pathology in a complex fashion, that is, via... (Review)
Review
Aberrant RNA structure and function operate in neurological disease progression and severity. As RNA contributes to disease pathology in a complex fashion, that is, via various mechanisms, it has become an attractive therapeutic target for small molecules and oligonucleotides. In this review, we discuss the identification of RNA structures that cause or contribute to neurological diseases as well as recent progress toward the development of small molecules that target them, including small molecule modulators of pre-mRNA splicing and RNA repeat expansions that cause microsatellite disorders such as Huntington's disease and amyotrophic lateral sclerosis. The use of oligonucleotide-based modalities is also discussed. There are key differences between small molecule and oligonucleotide targeting of RNA. The former targets RNA structure, while the latter prefers unstructured regions. Thus, some targets will be preferentially targeted by oligonucleotides and others by small molecules.
Topics: Amyotrophic Lateral Sclerosis; Humans; Huntington Disease; Nervous System Diseases; Nucleic Acid Conformation; Oligonucleotides; RNA; RNA Precursors; RNA Splicing; Small Molecule Libraries
PubMed: 30964958
DOI: 10.1111/nyas.14051 -
ACS Omega Jan 2020The electrochemical interface is an ultrathin interfacial region between the electrode and solution where electrochemical reactions occur. The study of the... (Review)
Review
The electrochemical interface is an ultrathin interfacial region between the electrode and solution where electrochemical reactions occur. The study of the electrochemical interface continues to be one of the most exciting directions in modern electrochemistry research. Much of our existing knowledge about the electrochemical interface comes from ensemble measurements and imaging of the electrode surface. Due to its enormous complexity and highly dynamic nature, however, new imaging tools that can probe the interface with ultrahigh spatial and temporal resolution and single-molecule sensitivity are apparently needed. Single-molecule fluorescence microscopy (SMFM) has emerged as a powerful tool that is uniquely suited for studying the electrochemical interface. In this mini-review, we first give a brief overview of various existing SMFM methods for studying electrochemical problems. We then discuss several exciting research topics involving the use of SMFM methods for studying surface-immobilized molecules, single freely diffusing molecules, single molecules as catalytic reaction indicators, and single-molecule labeling and imaging of interfacial nanobubbles. We anticipate that we will continue to see a rapid increase in publications on stochastic electrochemistry of single molecules and nanoparticles. The increased use of SMFM will likely bring new information to our study of the electrochemical interface.
PubMed: 31956755
DOI: 10.1021/acsomega.9b03763 -
Biomedicine & Pharmacotherapy =... Sep 2023Plant bioactive molecules could play key preventive and therapeutic roles in chronological aging and the pathogenesis of many chronic diseases, often accompanied by... (Review)
Review
Plant bioactive molecules could play key preventive and therapeutic roles in chronological aging and the pathogenesis of many chronic diseases, often accompanied by increased oxidative stress and low-grade inflammation. Dietary antioxidants, including genkwanin, could decrease oxidative stress and the expression of pro-inflammatory cytokines or pathways. The present study is the first comprehensive review of genkwanin, a methoxyflavone found in several plant species. Indeed, natural sources, and pharmacokinetics of genkwanin, the biological properties were discussed and highlighted in detail. This review analyzed and considered all original studies related to identification, isolation, quantification, investigation of the biological and pharmacological properties of genkwanin. We consulted all published papers in peer-reviewed journals in the English language from the inception of each database to 12 May 2023. Different phytochemical demonstrated that genkwanin is a non-glycosylated flavone found and isolated from several medicinal plants such as Genkwa Flos, Rosmarinus officinalis, Salvia officinalis, and Leonurus sibiricus. In vitro and in vivo biological and pharmacological investigations showed that Genkwanin exhibits remarkable antioxidant and anti-inflammatory activities, genkwanin, via activation of glucokinase, has shown antihyperglycemic activity with a potential role against metabolic syndrome and diabetes. Additionally, it revealed cardioprotective and neuroprotective properties, thus reducing the risk of cardiovascular diseases and assisting against neurodegenerative diseases. Furthermore, genkwanin showed other biological properties like antitumor capability, antibacterial, antiviral, and dermato-protective effects. The involved mechanisms include sub-cellular, cellular and molecular actions at different levels such as inducing apoptosis and inhibiting the growth and proliferation of cancer cells. Despite the findings from preclinical studies that have demonstrated the effects of genkwanin and its diverse mechanisms of action, additional research is required to comprehensively explore its therapeutic potential. Primarily, extensive studies should be carried out to enhance our understanding of the molecule's pharmacodynamic actions and pharmacokinetic pathways. Moreover, toxicological and clinical investigations should be undertaken to assess the safety and clinical efficacy of genkwanin. These forthcoming studies are of utmost importance in fully unlocking the potential of this molecule in the realm of therapeutic applications.
Topics: Flavones; Anti-Inflammatory Agents; Cytokines; Plant Extracts; Antioxidants
PubMed: 37481929
DOI: 10.1016/j.biopha.2023.115159