Functionalized Macrocyclic Compounds: Potential Sensors of Small Molecules and Ions

2003 ◽  
Vol 56 (4) ◽  
pp. 239 ◽  
Author(s):  
Paul V. Bernhardt ◽  
Evan G. Moore
Keyword(s):  
Small Molecules ◽  
Real World ◽  
Macrocyclic Compounds ◽  
Binding Mechanism ◽  
Sensor Applications ◽  
Potential Applications

The potential applications of macrocycles in chemistry and at its interfaces with biology and physics continue to emerge, one of which is as receptors for small molecules and ions. This review illustrates these applications with examples from the last ten years employing complexation as the binding mechanism; some of the systems presented have already found real-world sensor applications. In any case, the challenges remain to design more selective and sensitive receptors for guests.

Computational and Experimental Binding Mechanism of DNA-drug Interactions

2019 ◽  
Vol 24 (32) ◽  
pp. 3739-3757 ◽  
Author(s):  
Chandrabose Selvaraj ◽  
Sanjeev K. Singh
Keyword(s):  
Small Molecules ◽  
Self Assembly ◽  
Genetic Material ◽  
Dna Interaction ◽  
Significant Feature ◽  
Drug Molecules ◽  
Potential Applications ◽  
Novel Drug ◽  
Groove Binders ◽  
Molecular Docking And Dynamics

Nucleic acid is the key unit and a predominant genetic material for interpreting the fundamental basis of genetic information in an organism and now it is used for the evolution of a novel group of therapeutics. To identify the potential impact on the biological science, it receives high recognition in therapeutic applications. Due to its selective recognition of molecular targets and pathways, DNA significantly imparts tremendous specificity of action. Examining the properties of DNA holds numerous advantages in assembly, interconnects, computational elements, along with potential applications of DNA self-assembly and scaffolding include nanoelectronics, biosensors, and programmable/autonomous molecular machines. The interaction of low molecular weight, small molecules with DNA is a significant feature in pharmacology. Based on the mode of binding mechanisms, small molecules are categorized as intercalators and groove binders having a significant role in target-based drug development. The understanding mechanism of drug-DNA interaction plays an important role in the development of novel drug molecules with more effective and lesser side effects. This article attempts to outline those interactions of drug-DNA with both experimental and computational advances, including ultraviolet (UV) -visible spectroscopy, fluorescent spectroscopy, circular dichroism, nuclear magnetic resonance (NMR), molecular docking and dynamics, and quantum mechanical applications.

scholarly journals Binding Ensembles of p53-MDM2 Peptide Inhibitors by Combining Bayesian Inference and Atomistic Simulations

Molecules ◽  
2021 ◽  
Vol 26 (1) ◽  
pp. 198
Author(s):  
Lijun Lang ◽  
Alberto Perez
Keyword(s):  
Bayesian Inference ◽  
Virtual Screening ◽  
Statistical Mechanics ◽  
Small Molecules ◽  
Rational Design ◽  
Driving Forces ◽  
Peptide Inhibitors ◽  
Atomistic Simulations ◽  
Binding Mechanism ◽  
Intrinsically Disordered

Designing peptide inhibitors of the p53-MDM2 interaction against cancer is of wide interest. Computational modeling and virtual screening are a well established step in the rational design of small molecules. But they face challenges for binding flexible peptide molecules that fold upon binding. We look at the ability of five different peptides, three of which are intrinsically disordered, to bind to MDM2 with a new Bayesian inference approach (MELD × MD). The method is able to capture the folding upon binding mechanism and differentiate binding preferences between the five peptides. Processing the ensembles with statistical mechanics tools depicts the most likely bound conformations and hints at differences in the binding mechanism. Finally, the study shows the importance of capturing two driving forces to binding in this system: the ability of peptides to adopt bound conformations (ΔGconformation) and the interaction between interface residues (ΔGinteraction).

scholarly journals Sodium, Silver and Lithium-Ion Conducting β″-Alumina + YSZ Composites, Ionic Conductivity and Stability

Crystals ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 293
Author(s):  
Liangzhu Zhu ◽  
Anil V. Virkar
Keyword(s):  
Ion Exchange ◽  
Electrochemical Impedance ◽  
Ionic Conductivities ◽  
Lithium Ion ◽  
Co2 Corrosion ◽  
Ionic Conductors ◽  
Ion Conductor ◽  
Sensor Applications ◽  
Potential Applications ◽  
Ion Conducting

Na-β″-alumina (Na2O.~6Al2O3) is known to be an excellent sodium ion conductor in battery and sensor applications. In this study we report fabrication of Na- β″-alumina + YSZ dual phase composite to mitigate moisture and CO2 corrosion that otherwise can lead to degradation in pure Na-β″-alumina conductor. Subsequently, we heat-treated the samples in molten AgNO3 and LiNO3 to respectively form Ag-β″-alumina + YSZ and Li-β″-alumina + YSZ to investigate their potential applications in silver- and lithium-ion solid state batteries. Ion exchange fronts were captured via SEM and EDS techniques. Their ionic conductivities were measured using electrochemical impedance spectroscopy. Both ion exchange rates and ionic conductivities of these composite ionic conductors were firstly reported here and measured as a function of ion exchange time and temperature.

A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery

2013 ◽  
Vol 451 (2) ◽  
pp. 313-328 ◽  
Author(s):  
Yinghong Gao ◽  
Stephen P. Davies ◽  
Martin Augustin ◽  
Anna Woodward ◽  
Umesh A. Patel ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Drug Discovery ◽  
Small Molecules ◽  
Chemical Structure ◽  
Rational Design ◽  
Kinase Inhibitors ◽  
Biochemical Assays ◽  
Potential Applications ◽  
Specific Inhibitors ◽  
Target Effects

Despite the development of a number of efficacious kinase inhibitors, the strategies for rational design of these compounds have been limited by target promiscuity. In an effort to better understand the nature of kinase inhibition across the kinome, especially as it relates to off-target effects, we screened a well-defined collection of kinase inhibitors using biochemical assays for inhibitory activity against 234 active human kinases and kinase complexes, representing all branches of the kinome tree. For our study we employed 158 small molecules initially identified in the literature as potent and specific inhibitors of kinases important as therapeutic targets and/or signal transduction regulators. Hierarchical clustering of these benchmark kinase inhibitors on the basis of their kinome activity profiles illustrates how they relate to chemical structure similarities and provides new insights into inhibitor specificity and potential applications for probing new targets. Using this broad dataset, we provide a framework for assessing polypharmacology. We not only discover likely off-target inhibitor activities and recommend specific inhibitors for existing targets, but also identify potential new uses for known small molecules.

scholarly journals Scope of 3D Shape-Based Approaches in Predicting the Macromolecular Targets of Structurally Complex Small Molecules Including Natural Products and Macrocyclic Ligands

2020 ◽  
Author(s):  
Ya Chen ◽  
Neann Mathai ◽  
Johannes Kirchmair
Keyword(s):  
Natural Products ◽  
Small Molecules ◽  
Knowledge Base ◽  
Target Prediction ◽  
Molecular Shape ◽  
Macrocyclic Compounds ◽  
Success Rates ◽  
Complex Molecules ◽  
Complete Failure ◽  
Prediction Approach

A plethora of similarity-based, network-based, machine learning and docking approaches for predicting the macromolecular targets of small molecules are available today and recognized as valuable tools for providing guidance in early drug discovery. With the increasing maturity of target prediction methods, researchers have started to explore ways to expand their scope to more challenging molecules such as structurally complex natural products and macrocyclic small molecules. In this work we systematically explore the capacity of an alignment-based approach to identify the targets of structurally complex small molecules (including large and flexible natural products and macrocyclic compounds) based on the similarity of their 3D molecular shape to non-complex molecules (i.e. more conventional, "drug-like", synthetic compounds). For this analysis, query sets of ten representative, structurally complex molecules were compiled for each of 35 pharmaceutically relevant proteins. Subsequently, ROCS, a leading shape-based screening engine, was utilized to generate rank-ordered lists of the potential targets of the 35x10 queries according to the similarity of their 3D molecular shape with that of compounds from a knowledge base of 272 640 non-complex small molecules active on a total of 3642 different proteins. Four of the scores implemented in ROCS were explored for target ranking, with the TanimotoCombo score consistently outperforming all others. The score successfully recovered the targets of 29% and 40% of the 350 queries among the top-5 and top-20 positions, respectively. For 29 out of the 35 investigated targets (83%), the method correctly assigned the first rank (out of 3642) to the target of interest for at least one of the ten queries. The shape-based target prediction approach showed remarkable robustness, with good success rates obtained even for compounds that are clearly distinct from any of the ligands present in the knowledge base. However, complex natural products and macrocyclic compounds proved to be challenging even with this approach, although cases of complete failure were recorded only for a small number of targets.

scholarly journals Gene mining, codon optimization and analysis of binding mechanism of an aldo-keto reductase with high activity, better substrate specificity and excellent solvent tolerance

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0260787
Author(s):  
Wei Jiang ◽  
Xiaoli Fu ◽  
Weiliang Wu
Keyword(s):  
High Activity ◽  
Organic Solvents ◽  
Catalytic Reduction ◽  
Antidepressant Drug ◽  
Reaction System ◽  
Solvent Tolerance ◽  
Chiral Alcohols ◽  
Binding Mechanism ◽  
Potential Applications ◽  
Mediated Reduction

The biosynthesis of chiral alcohols has important value and high attention. Aldo–keto reductases (AKRs) mediated reduction of prochiral carbonyl compounds is an interesting way of synthesizing single enantiomers of chiral alcohols due to the high enantio-, chemo- and regioselectivity of the enzymes. However, relatively little research has been done on characterization and apply of AKRs to asymmetric synthesis of chiral alcohols. In this study, the AKR from Candida tropicalis MYA-3404 (C. tropicalis MYA-3404), was mined and characterized. The AKR shown wider optimum temperature and pH. The AKR exhibited varying degrees of catalytic activity for different substrates, suggesting that the AKR can catalyze a variety of substrates. It is worth mentioning that the AKR could catalytic reduction of keto compounds with benzene rings, such as cetophenone and phenoxyacetone. The AKR exhibited activity on N,N-dimethyl-3-keto-3-(2-thienyl)-1-propanamine (DKTP), a key intermediate for biosynthesis of the antidepressant drug duloxetine. Besides, the AKR still has high activity whether in a reaction system containing 10%-30% V/V organic solvent. What’s more, the AKR showed the strongest stability in six common organic solvents, DMSO, acetonitrile, ethyl acetate, isopropanol, ethanol, and methanol. And, it retains more that 70% enzyme activity after 6 hours, suggesting that the AKR has strong solvent tolerance. Furthermore, the protein sequences of the AKR and its homology were compared, and a 3D model of the AKR docking with coenzyme NADPH were constructed. And the important catalytic and binding sites were identified to explore the binding mechanism of the enzyme and its coenzyme. These properties, predominant organic solvents resistance and extensive substrate spectrum, of the AKR making it has potential applications in the pharmaceutical field.

scholarly journals Biosensors design in yeast and applications in metabolic engineering

2019 ◽  
Vol 19 (8) ◽  
Author(s):  
Chenxi Qiu ◽  
Haotian Zhai ◽  
Jin Hou
Keyword(s):  
Metabolic Engineering ◽  
Small Molecules ◽  
High Throughput ◽  
Cell Level ◽  
High Throughput Analysis ◽  
New Techniques ◽  
Dynamic Regulation ◽  
Sensor Applications ◽  
Microbial Cell Factories ◽  
Cell Factories

ABSTRACT Engineering microbial cell factories is a potential approach of sustainable production of chemicals, fuels and pharmaceuticals. However, testing the production of molecules in high throughput is still a time-consuming and laborious process since product synthesis usually does not confer a clear phenotype. Therefore, it is necessary to develop new techniques for fast high-producer screening. Genetically encoded biosensors are considered to be promising devices for high-throughput analysis owing to their ability to sense metabolites and couple detection to an actuator, thereby facilitating the rapid detection of small molecules at single-cell level. Here, we review recent advances in the design and engineering of biosensors in Saccharomyces cerevisiae, and their applications in metabolic engineering. Three types of biosensor are introduced in this review: transcription factor based, RNA-based and enzyme-coupled biosensors. The studies to improve the features of biosensors are also described. Moreover, we summarized their metabolic engineering applications in dynamic regulation and high producer selection. Current challenges in biosensor design and future perspectives on sensor applications are also discussed.

scholarly journals Numerical Approaches to Fractional Integrals and Derivatives: A Review

Mathematics ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 43 ◽  
Author(s):  
Min Cai ◽  
Changpin Li
Keyword(s):  
Fractional Calculus ◽  
Real World ◽  
Mathematical Concept ◽  
Fractional Integrals ◽  
Numerical Approximations ◽  
The Real ◽  
Potential Applications ◽  
Fractional Integrals And Derivatives ◽  
Almost All ◽  
Numerical Approaches

Fractional calculus, albeit a synonym of fractional integrals and derivatives which have two main characteristics—singularity and nonlocality—has attracted increasing interest due to its potential applications in the real world. This mathematical concept reveals underlying principles that govern the behavior of nature. The present paper focuses on numerical approximations to fractional integrals and derivatives. Almost all the results in this respect are included. Existing results, along with some remarks are summarized for the applied scientists and engineering community of fractional calculus.

NaviCam:A Magnifying Glass Approach to Augmented Reality

1997 ◽  
Vol 6 (4) ◽  
pp. 399-412 ◽  
Author(s):  
Jun Rekimoto
Keyword(s):  
Augmented Reality ◽  
Real World ◽  
Video Camera ◽  
Display Device ◽  
Daily Lives ◽  
The Real ◽  
Video Images ◽  
Potential Applications ◽  
Subjective Score ◽  
Tracking Devices

Current augmented reality (AR) systems are not designed to be used in our daily lives. Head-mounted see-through displays are too cumbersome and look too unusual for everyday life. The limited scalability of position-tracking devices limits the use of AR to very restricted environments. This paper proposes a different way to realize AR that can be used in an open environment by introducing the concept of ID awareness and a hand-held video see-through display. Unlike other AR systems that use head-mounted or head-up displays, our approach employs the combination of a palmtop-sized display and a small video camera. A user sees the real world through the display device, with added computer-augmented information. We call this configuration the magnifying glass approach. It has several advantages over traditional head-up or head-mounted configurations. The main advantage is that the user is not required to wear any cumbersome headgear. The user can easily move the display device around like a magnifying glass and compare real and augmented images. The video camera also obtains information related to real-world situations. The system recognizes real-world objects using the video images by reading identification (ID) tags. Based on the recognized ID tag, the system retrieves and displays information about the real-world object to the user. The prototype hand-held device based on our proposed concept is called NaviCam. We describe several potential applications. Our experiments with NaviCam show the great potential of our video see-through palmtop display. It was significantly faster than a head-up configuration, and its subjective score from testers was also higher.

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