scholarly journals Theoretical Three-Dimensional Zinc Complexes with Glutathione, Amino Acids and Flavonoids

Stresses ◽  
2021 ◽  
Vol 1 (3) ◽  
pp. 123-141
Author(s):  
José Manuel Pérez de la Lastra ◽  
Celia Andrés-Juan ◽  
Francisco J. Plou ◽  
Eduardo Pérez-Lebeña
Keyword(s):  
Amino Acids ◽  
Energy Content ◽  
Three Dimensional ◽  
Cellular Level ◽  
Zinc Complexes ◽  
Conformational Structure ◽  
Cellular Functions ◽  
Potential Health ◽  
Intracellular Zinc ◽  
Extracellular Stimuli

Zinc plays an important role in the regulation of many cellular functions; it is a signaling molecule involved in the transduction of several cascades in response to intra and extracellular stimuli. Labile zinc is a small fraction of total intracellular zinc, that is loosely bound to proteins and is easily interchangeable. At the cellular level, several molecules can bind labile zinc and promote its passage across lipophilic membranes. Such molecules are known as ionophores. Several of these compounds are known in the scientific literature, but most of them can be harmful to human health and are therefore not allowed for medical use. We here performed a theoretical three-dimensional study of known zinc ionophores, together with a computational energetic study and propose that some dietary flavonoids, glutathione and amino acids could form zinc complexes and facilitate the transport of zinc, with the possible biological implications and potential health benefits of these natural compounds. The study is based on obtaining a molecular conformational structure of the zinc complexes with the lowest possible energy content. The discovery of novel substances that act as zinc ionophores is an attractive research topic that offers exciting opportunities in medicinal chemistry. We propose that these novel complexes could be promising candidates for drug design to provide new solutions for conditions and diseases related to zinc deficiency or impairment derived from the dysregulation of this important metal.

Probing Cytoskeletal Mechanics Using Biochemical Inhibitors

2010 ◽  
Author(s):  
Kenneth M. Pryse ◽  
Teresa M. Abney ◽  
Guy M. Genin ◽  
Elliot L. Elson
Keyword(s):  
Extracellular Matrix ◽  
Mechanical Testing ◽  
Three Dimensional ◽  
Cellular Level ◽  
Cellular Migration ◽  
Cellular Functions ◽  
Form And Function ◽  
Tissue Constructs ◽  
Imaging Results ◽  
And Function

Quantifying the mechanics of the cytoskeletons of living cells is important for understanding several physiologic and pathologic cellular functions, such as wound healing and cellular migration in cancer. Our laboratory develops three-dimensional tissue constructs for assaying cytoskeletal mechanics in controlled conditions. These tissue constructs consist of defined components such as chick embryo fibroblasts and reconstituted rat tail collagen; fibroblasts remodel the collagen extracellular matrix (ECM) and develop a structural environment representative of that which would exist in a natural tissue. Our protocol for quantifying the microscale mechanics of the proteins that comprise the cytoskeleton involves mechanical testing of a tissue construct first in a bath that contains nutrition medium to support the active physiologic functioning of the cells, and next in the presence of inhibitors that selectively eliminate specific cytoskeletal structures. By solving an inverse homogenization problem, the mechanical functioning of these proteins at the cellular level can be estimated. Here, we present a combination of mechanical testing and imaging results to quantify the effects of specific inhibitors on cytoskeletal and extracellular matrix form and function.

Multimode light microscopy and fluorescence-based reagents as tools for the study of chemical and molecular dynamics of living cells and tissues

1992 ◽  
Vol 50 (1) ◽  
pp. 418-419
Author(s):  
D. L. Taylor
Keyword(s):  
Living Cells ◽  
Cellular Level ◽  
Molecular Techniques ◽  
Cellular Functions ◽  
Macromolecular Assemblies ◽  
Cell Functions ◽  
Molecular Events ◽  
Yield Information ◽  
Full Knowledge ◽  
Structural Methods

Cells function through the complex temporal and spatial interplay of ions, metabolites, macromolecules and macromolecular assemblies. Biochemical approaches allow the investigator to define the components and the solution chemical reactions that might be involved in cellular functions. Static structural methods can yield information concerning the 2- and 3-D organization of known and unknown cellular constituents. Genetic and molecular techniques are powerful approaches that can alter specific functions through the manipulation of gene products and thus identify necessary components and sequences of molecular events. However, full knowledge of the mechanism of particular cell functions will require direct measurement of the interplay of cellular constituents. Therefore, there has been a need to develop methods that can yield chemical and molecular information in time and space in living cells, while allowing the integration of information from biochemical, molecular and genetic approaches at the cellular level.

scholarly journals Advancing Drug Discovery for Neurological Disorders Using iPSC-Derived Neural Organoids

2021 ◽  
Vol 22 (5) ◽  
pp. 2659
Author(s):  
Gianluca Costamagna ◽  
Giacomo Pietro Comi ◽  
Stefania Corti
Keyword(s):  
Drug Discovery ◽  
Drug Screening ◽  
Neural Development ◽  
Neurological Disorders ◽  
Large Scale ◽  
Three Dimensional ◽  
Induced Pluripotent Stem Cell ◽  
Cellular Level ◽  
Complex Data ◽  
Complex Data Sets

In the last decade, different research groups in the academic setting have developed induced pluripotent stem cell-based protocols to generate three-dimensional, multicellular, neural organoids. Their use to model brain biology, early neural development, and human diseases has provided new insights into the pathophysiology of neuropsychiatric and neurological disorders, including microcephaly, autism, Parkinson’s disease, and Alzheimer’s disease. However, the adoption of organoid technology for large-scale drug screening in the industry has been hampered by challenges with reproducibility, scalability, and translatability to human disease. Potential technical solutions to expand their use in drug discovery pipelines include Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) to create isogenic models, single-cell RNA sequencing to characterize the model at a cellular level, and machine learning to analyze complex data sets. In addition, high-content imaging, automated liquid handling, and standardized assays represent other valuable tools toward this goal. Though several open issues still hamper the full implementation of the organoid technology outside academia, rapid progress in this field will help to prompt its translation toward large-scale drug screening for neurological disorders.

scholarly journals Applications of Biomaterials in 3D Cell Culture and Contributions of 3D Cell Culture to Drug Development and Basic Biomedical Research

2021 ◽  
Vol 22 (5) ◽  
pp. 2491
Author(s):  
Yujin Park ◽  
Kang Moo Huh ◽  
Sun-Woong Kang
Keyword(s):  
Cell Culture ◽  
Three Dimensional ◽  
3D Culture ◽  
3D Cell Culture ◽  
Accurate Method ◽  
New Drugs ◽  
Toxicity Screening ◽  
Cellular Functions ◽  
Toxicity Of Drugs ◽  
External Stimuli

The process of evaluating the efficacy and toxicity of drugs is important in the production of new drugs to treat diseases. Testing in humans is the most accurate method, but there are technical and ethical limitations. To overcome these limitations, various models have been developed in which responses to various external stimuli can be observed to help guide future trials. In particular, three-dimensional (3D) cell culture has a great advantage in simulating the physical and biological functions of tissues in the human body. This article reviews the biomaterials currently used to improve cellular functions in 3D culture and the contributions of 3D culture to cancer research, stem cell culture and drug and toxicity screening.

scholarly journals Mycosporine-Like Amino Acids: Potential Health and Beauty Ingredients

Marine Drugs ◽  
2017 ◽  
Vol 15 (10) ◽  
pp. 326 ◽  
Author(s):  
Ewelina Chrapusta ◽  
Ariel Kaminski ◽  
Kornelia Duchnik ◽  
Beata Bober ◽  
Michal Adamski ◽  
...  
Keyword(s):  
Amino Acids ◽  
Potential Health

scholarly journals Visual pH Sensors: From a Chemical Perspective to New Bioengineered Materials

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 2952
Author(s):  
Luigi Di Costanzo ◽  
Barbara Panunzi
Keyword(s):  
Ph Monitoring ◽  
Three Dimensional ◽  
Lessons Learned ◽  
Background Information ◽  
Biological Macromolecules ◽  
Ph Sensing ◽  
Ph Sensors ◽  
Cellular Functions ◽  
Metal Organic

Many human activities and cellular functions depend upon precise pH values, and pH monitoring is considered a fundamental task. Colorimetric and fluorescence sensors for pH measurements are chemical and biochemical tools able to sense protons and produce a visible signal. These pH sensors are gaining widespread attention as non-destructive tools, visible to the human eye, that are capable of a real-time and in-situ response. Optical “visual” sensors are expanding researchers’ interests in many chemical contexts and are routinely used for biological, environmental, and medical applications. In this review we provide an overview of trending colorimetric, fluorescent, or dual-mode responsive visual pH sensors. These sensors include molecular synthetic organic sensors, metal organic frameworks (MOF), engineered sensing nanomaterials, and bioengineered sensors. We review different typological chemical entities of visual pH sensors, three-dimensional structures, and signaling mechanisms for pH sensing and applications; developed in the past five years. The progression of this review from simple organic molecules to biological macromolecules seeks to benefit beginners and scientists embarking on a project of pH sensing development, who needs background information and a quick update on advances in the field. Lessons learned from these tools will aid pH determination projects and provide new ways of thinking for cell bioimaging or other cutting-edge in vivo applications.

scholarly journals Isolation, purification and structure of exochelin MS, the extracellular siderophore from Mycobacterium smegmatis

1995 ◽  
Vol 305 (1) ◽  
pp. 187-196 ◽  
Author(s):  
G J Sharman ◽  
D H Williams ◽  
D F Ewing ◽  
C Ratledge
Keyword(s):  
Amino Acids ◽  
Mycobacterium Smegmatis ◽  
Methyl Esters ◽  
Three Dimensional ◽  
Iron Chelation ◽  
Peptide Bond ◽  
Exchange Chromatography ◽  
Peptide Bonds ◽  
Hydrolysis Of ◽  
Gallium Complex

The extracellular siderophore from Mycobacterium smegmatis, exochelin MS, was isolated from iron-deficiently grown cultures and purified to > 98% by a combination of ion-exchange chromatography and h.p.l.c. The material is unextractable into organic solvents, is basic (pI = 9.3-9.5), has a lambda max at 420 nm and a probable Ks for Fe3+ of between 10(25) and 10(30). Its structure has been determined by examination of desferri- and ferri-exochelin and its gallium complex. The methods used were electrospray-m.s. and one- and two-dimensional (NOESY, DQF-COSY and TOCSY) 1H n.m.r. The constituent amino acids were examined by chiral g.l.c analysis of N-trifluoroacetyl isopropyl and N-pentafluoropropionyl methyl esters after hydrolysis, and reductive HI hydrolysis, of the siderophore. The exochelin is a formylated pentapeptide: N-(delta-N-formyl,delta N-hydroxy-R-ornithyl) -beta-alaninyl-delta N-hydroxy-R-ornithinyl-R-allo-threoninyl-delta N-hydroxy-S-ornithine. The linkages involving the three ornithine residues are via their delta N(OH) and alpha-CO groups leaving three free alpha-NH2 groups. Although there are two peptide bonds, these involve the three R (D)-amino acids. Thus the molecule has no conventional peptide bond, and this suggests that it will be resistant to peptidase hydrolysis. The co-ordination centre with Fe3+ is hexadenate in an octahedral structure involving the three hydroxamic acid groups. Molecular modelling shows it to have similar features to other ferric trihydroxamate siderophores whose three-dimensional structures have been established. The molecule is shown to have little flexibility around the iron chelation centre, although the terminal (Orn-3) residue, which is not involved in iron binding except at its delta N atom, has more motional freedom.

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