11 research outputs found
New Advances in Fast Methods of 2D NMR Experiments
Although nuclear magnetic resonance spectroscopy is a potent analytical tool for identification, quantification, and structural elucidation, it suffers from inherently low sensitivity limitations. This chapter focuses on recently reported methods that enable quick acquisition of NMR spectra, as well as new methods of faster, efficient, and informative two-dimensional (2D) NMR methods. Fast and efficient data acquisition has risen in response to an increasing need to investigate chemical and biological processes in real time. Several new techniques have been successfully introduced. One example of this is band-selective optimized-flip-angle short-transient (SOFAST) NMR, which has opened the door to studying the kinetics of biological processes such as the phosphorylation of proteins. The fast recording of NMR spectra allows researchers to investigate time sensitive molecules that have limited stability under experimental conditions. The increasing awareness that molecular structures are dynamic, rather than static, has pushed some researchers to find alternatives to standard, time-consuming methods of 15N relaxation observables acquisition
The Best Peptidomimetic Strategies to Undercover Antibacterial Peptides
Health-care systems that develop rapidly and efficiently may increase the lifespan of humans. Nevertheless, the older population is more fragile, and is at an increased risk of disease development. A concurrently growing number of surgeries and transplantations have caused antibiotics to be used much more frequently, and for much longer periods of time, which in turn increases microbial resistance. In 1945, Fleming warned against the abuse of antibiotics in his Nobel lecture: âThe time may come when penicillin can be bought by anyone in the shops. Then there is the danger that the ignorant man may easily underdose himself and by exposing his microbes to non-lethal quantities of the drug make them resistantâ. After 70 years, we are witnessing the fulfilment of Flemingâs prophecy, as more than 700,000 people die each year due to drug-resistant diseases. Naturally occurring antimicrobial peptides protect all living matter against bacteria, and now different peptidomimetic strategies to engineer innovative antibiotics are being developed to defend humans against bacterial infections
You are what you eat: Application of Metabolomics Approaches to Advance Nutrition Research
A healthy condition is defined by complex human metabolic pathways that only function
properly when fully satisfied by nutritional inputs. Poor nutritional intakes are associated with a
number of metabolic diseases, such as diabetes, obesity, atherosclerosis, hypertension, and osteoporosis.
In recent years, nutrition science has undergone an extraordinary transformation driven
by the development of innovative software and analytical platforms. However, the complexity and
variety of the chemical components present in different food types, and the diversity of interactions
in the biochemical networks and biological systems, makes nutrition research a complicated field.
Metabolomics science is an â-omicâ, joining proteomics, transcriptomics, and genomics in affording a
global understanding of biological systems. In this review, we present the main metabolomics approaches,
and highlight the applications and the potential for metabolomics approaches in advancing
nutritional food research
NMR as a âgold standardâ method in drug design and discovery
Studying disease models at the molecular level is vital for drug development in order to improve treatment and prevent a wide range of human pathologies. Microbial infections are still a major challenge because pathogens rapidly and continually evolve developing drug resistance. Cancer cells also change genetically, and current therapeutic techniques may be (or may become) ineffective in many cases. The pathology of many neurological diseases remains an enigma, and the exact etiology and underlying mechanisms are still largely unknown. Viral infections spread and develop much more quickly than does the corresponding research needed to prevent and combat these infections; the present and most relevant outbreak of SARS-CoV-2, which originated in Wuhan, China, illustrates the critical and immediate need to improve drug design and development techniques. Modern day drug discovery is a time-consuming, expensive process. Each new drug takes in excess of 10 years to develop and costs on average more than a billion US dollars. This demonstrates the need of a complete redesign or novel strategies. Nuclear Magnetic Resonance (NMR) has played a critical role in drug discovery ever since its introduction several decades ago. In just three decades, NMR has become a âgold standardâ platform technology in medical and pharmacology studies. In this review, we present the major applications of NMR spectroscopy in medical drug discovery and development. The basic concepts, theories, and applications of the most commonly used NMR techniques are presented. We also summarize the advantages and limitations of the primary NMR methods in drug development
Thymosin β4 Is an Endogenous Iron Chelator and Molecular Switcher of Ferroptosis
Thymosin β4 (Tβ4) was extracted forty years agofrom calf thymus. Since then, it has been identified as a G-actin binding protein involved in blood clotting, tissue regeneration, angiogenesis, and anti-inflammatory processes. Tβ4 has also been implicated in tumor metastasis and neurodegeneration. However, the precise roles and mechanism(s) of action of Tβ4 in these processes remain largely unknown, with the binding of the G-actin protein being insufficient to explain these multi-actions. Here we identify for the first time the important role of Tβ4 mechanism in ferroptosis, an iron-dependent form of cell death, which leads to neurodegeneration and somehow protects cancer cells against cell death. Specifically, we demonstrate four iron2+ and iron3+ binding regions along the peptide and show that the presence of Tβ4 in cell growing medium inhibits erastin and glutamate-induced ferroptosis in the macrophage cell line. Moreover, Tβ4 increases the expression of oxidative stress-related genes, namely BAX, hem oxygenase-1, heat shock protein 70 and thioredoxin reductase 1, which are downregulated during ferroptosis. We state the hypothesis that Tβ4 is an endogenous iron chelator and take part in iron homeostasis in the ferroptosis process. We discuss the literature data of parallel involvement of Tβ4 and ferroptosis in different human pathologies, mainly cancer and neurodegeneration. Our findings confronted with literature data show that controlled Tβ4 release could command on/off switching of ferroptosis and may provide novel therapeutic opportunities in cancer and tissue degeneration pathologies.Financial support from FIR 2019 and from Regione Autonoma della Sardegna (grant RASSR79857) is gratefully acknowledged
Fluxomics - New Metabolomics Approaches to Monitor Metabolic Pathways
Fluxomics is an innovative -omics research field that measures the rates of all intracellular fluxes in the central metabolism of biological systems. Fluxomics gathers data from multiple different -omics fields, portraying the whole picture of molecular interactions. Recently, fluxomics has become one of the most relevant approaches to investigate metabolic phenotypes. Metabolic flux using 13C-labeled molecules is increasingly used to monitor metabolic pathways, to probe the corresponding gene-RNA and protein-metabolite interaction networks in actual time. Thus, fluxomics reveals the functioning of multi-molecular metabolic pathways and is increasingly applied in biotechnology and pharmacology. Here, we describe the main fluxomics approaches and experimental platforms. Moreover, we summarize recent fluxomic results in different biological systems
Aggregation of biologically important peptides and proteins: inhibition or acceleration depending on protein and metal ion concentrations
The process of aggregation of proteins and peptides is dependent on the concentration of proteins, and the rate of aggregation can be altered by the presence of metal ions, but this dependence is not always a straightforward relationship. In general, aggregation does not occur under normal physiological conditions, yet it can be induced in the presence of certain metal ions. However, the extent of the influence of metal ion interactions on protein aggregation has not yet been fully comprehended. A consensus has thus been difficult to reach because the acceleration/inhibition of the aggregation of proteins in the presence of metal ions depends on several factors such as pH and the concentration of the aggregated proteins involved as well as metal concentration level of metal ions. Metal ions, like Cu2+, Zn2+, Pb2+ etc. may either accelerate or inhibit aggregation simply because the experimental conditions affect the behavior of biomolecules. It is clear that understanding the relationship between metal ion concentration and protein aggregation will prove useful for future scientific applications. This review focuses on the dependence of the aggregation of selected important biomolecules (peptides and proteins) on metal ion concentrations. We review proteins that are prone to aggregation, the result of which can cause serious neurodegenerative disorders. Furthering our understanding of the relationship between metal ion concentration and protein aggregation will prove useful for future scientific applications, such as finding therapies for neurodegenerative diseases
Pharmacometabolomics: A New Horizon in Personalized Medicine
Pharmacology is the predominant first-line treatment for most pathologies. However, various factors, such as genetics, gender, diet, and health status, significantly influence the efficacy of drugs in different patients, sometimes with fatal consequences. Personalized diagnosis substantially improves treatment efficacy but requires a more comprehensive process for health assessment. Pharmacometabolomics combines metabolomic, genomic, transcriptomic and proteomic approaches and therefore offers data that other analytical methods cannot provide. In this way, pharmacometabolomics more accurately guides medical professionals in predicting an individualâs response to selected drugs. In this chapter, we discuss the potentials and the advantages of metabolomics approaches for designing innovative and personalized drug treatments
Nuclear magnetic resonance in metabolomics
Nuclear magnetic resonance (NMR) is one of the most common and powerful techniques used in metabolomics. The inherent quantitative, nondestructive, and nonbiased properties, together with minimal sample preparation/manipulation make NMR a potent approach to any investigative metabolic study involving biological systems. NMR spectroscopy offers several unique monitoring opportunities such as extremely high reproducibility, relatively short experiment times, a wide range of available experiments (e.g., multidimensional and multinuclear based), and advanced highly automated robotic sample handling/exchange technologies enabling potentially hundreds of samples per instrument in a single day. In this chapter, we highlight the primary advantages and limitations of NMR spectroscopy, introduce the most commonly applied NMR experiments in metabolomics, and review some of the recent advances with selected examples of novel applications, such as high-resolution magic-angle spinning for tissue samples, and pure shift NMR method as an example of a promising new approach that can be used to overcome the overlapping of 1D NMR spectra. The main advantages of NMR spectroscopy with a particular focus on reproducibility are also presented
Attempting to synthesize lasso peptides using high pressure.
Lasso peptides are unique in that the tail of the lasso peptide threads through its macrolactam ring. The unusual structure and biological activity of lasso peptides have generated increased interest from the scientific community in recent years. Because of this, many new types of lasso peptides have been discovered. These peptides can be synthesized by microorganisms efficiently, and yet, their chemical assembly is challenging. Herein, we investigated the possibility of high pressure inducing the cyclization of linear precursors of lasso peptides. Unlike other molecules like rotaxanes which mechanically interlock at high pressure, the threaded lasso peptides did not form, even at pressures the high pressure up to 14 000 kbar