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Albumin transport function analysis by EPR spectroscopy is an in vitro blood test that detects changes to the transport and molecular conformation of serum albumin using the method of EPR spectroscopy. The test is used for diagnosis of cancer, sepsis and toxemia.
The test is based on the interaction of spin-labeled fatty acids with serum albumin by means of EPR spectroscopy. [1] [2] [3]
A sample of blood serum is subjected to a spin probe 16-doxyl stearate. Spin probe molecules bind specifically to albumin molecules where they occupy two main positions:
The spin probe molecules bound on albumin have restricted mobility that changes the EPR spectrum, which reflects characteristics of the protein site where the spin probe is located and allows estimating the conformation of the albumin globule. Some part of the spin probe remains in the serum in the unbound state. The ratio of the fractions of bound and unbound spin probes allows estimating the functional activity of albumin molecules. Analysis of the EPR spectrum allows assessment of the conformation and functional activity of albumin molecules.
The test material is 100 μL serum or plasma.
The procedure includes mixing a serum sample with a spin probe reagent, incubating the mixture, measuring the EPR spectrum of a serum with a spin probe, and analyzing the EPR spectrum by calculating the conformation and functional indicators of albumin molecules.
A specific change to the conformation of albumin molecules [4] [5] that is associated with the growth of a malignant tumor is caused by (or associated with) changes in the composition of metabolites carried by serum albumin during the growth of a malignant tumor [6] [7] (proliferating cancer cells uptake and release metabolites in abnormal quantities).
Clinical studies of the EPR test of serum albumin [8] [9] [10] [11] [12] showed diagnostic sensitivity and specificity of 90%.
Clinical applications:
Reduced functional activity of serum albumin (reduced binding efficacy) is associated with toxemia (an increase in the concentration of toxic molecules in the blood) and is manifested before other clinical symptoms.
Clinical applications:
Ascites is the abnormal build-up of fluid in the abdomen. Technically, it is more than 25 ml of fluid in the peritoneal cavity, although volumes greater than one liter may occur. Symptoms may include increased abdominal size, increased weight, abdominal discomfort, and shortness of breath. Complications can include spontaneous bacterial peritonitis.
α2-Macroglobulin (α2M) or alpha-2-macroglobulin is a large plasma protein found in the blood. It is mainly produced by the liver, and also locally synthesized by macrophages, fibroblasts, and adrenocortical cells. In humans it is encoded by the A2M gene.
Site-directed spin labeling (SDSL) is a technique for investigating the structure and local dynamics of proteins using electron spin resonance. The theory of SDSL is based on the specific reaction of spin labels with amino acids. A spin label's built-in protein structure can be detected by EPR spectroscopy. SDSL is also a useful tool in examinations of the protein folding process.
A tumor marker is a biomarker that can be used to indicate the presence of cancer or the behavior of cancers. They can be found in bodily fluids or tissue. Markers can help with assessing prognosis, surveilling patients after surgical removal of tumors, and even predicting drug-response and monitor therapy.
Microwave spectroscopy is the spectroscopy method that employs microwaves, i.e. electromagnetic radiation at GHz frequencies, for the study of matter.
Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy or magnetic resonance spectroscopy (MRS), is a spectroscopic technique based on re-orientation of atomic nuclei with non-zero nuclear spins in an external magnetic field. This re-orientation occurs with absorption of electromagnetic radiation in the radio frequency region from roughly 4 to 900 MHz, which depends on the isotopic nature of the nucleus and increased proportionally to the strength of the external magnetic field. Notably, the resonance frequency of each NMR-active nucleus depends on its chemical environment. As a result, NMR spectra provide information about individual functional groups present in the sample, as well as about connections between nearby nuclei in the same molecule. As the NMR spectra are unique or highly characteristic to individual compounds and functional groups, NMR spectroscopy is one of the most important methods to identify molecular structures, particularly of organic compounds.
Electron paramagnetic resonance (EPR) or electron spin resonance (ESR) spectroscopy is a method for studying materials that have unpaired electrons. The basic concepts of EPR are analogous to those of nuclear magnetic resonance (NMR), but the spins excited are those of the electrons instead of the atomic nuclei. EPR spectroscopy is particularly useful for studying metal complexes and organic radicals. EPR was first observed in Kazan State University by Soviet physicist Yevgeny Zavoisky in 1944, and was developed independently at the same time by Brebis Bleaney at the University of Oxford.
In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. The etymology stems from Latin ligare, which means 'to bind'. In protein-ligand binding, the ligand is usually a molecule which produces a signal by binding to a site on a target protein. The binding typically results in a change of conformational isomerism (conformation) of the target protein. In DNA-ligand binding studies, the ligand can be a small molecule, ion, or protein which binds to the DNA double helix. The relationship between ligand and binding partner is a function of charge, hydrophobicity, and molecular structure.
Molecular imaging is a field of medical imaging that focuses on imaging molecules of medical interest within living patients. This is in contrast to conventional methods for obtaining molecular information from preserved tissue samples, such as histology. Molecules of interest may be either ones produced naturally by the body, or synthetic molecules produced in a laboratory and injected into a patient by a doctor. The most common example of molecular imaging used clinically today is to inject a contrast agent into a patient's bloodstream and to use an imaging modality to track its movement in the body. Molecular imaging originated from the field of radiology from a need to better understand fundamental molecular processes inside organisms in a noninvasive manner.
Human serum albumin is the serum albumin found in human blood. It is the most abundant protein in human blood plasma; it constitutes about half of serum protein. It is produced in the liver. It is soluble in water, and it is monomeric.
In biochemistry, a conformational change is a change in the shape of a macromolecule, often induced by environmental factors.
Physical organic chemistry, a term coined by Louis Hammett in 1940, refers to a discipline of organic chemistry that focuses on the relationship between chemical structures and reactivity, in particular, applying experimental tools of physical chemistry to the study of organic molecules. Specific focal points of study include the rates of organic reactions, the relative chemical stabilities of the starting materials, reactive intermediates, transition states, and products of chemical reactions, and non-covalent aspects of solvation and molecular interactions that influence chemical reactivity. Such studies provide theoretical and practical frameworks to understand how changes in structure in solution or solid-state contexts impact reaction mechanism and rate for each organic reaction of interest.
α-Parinaric acid is a conjugated polyunsaturated fatty acid. Discovered by Tsujimoto and Koyanagi in 1933, it contains 18 carbon atoms and 4 conjugated double bonds. The repeating single bond-double bond structure of α-parinaric acid distinguishes it structurally and chemically from the usual "methylene-interrupted" arrangement of polyunsaturated fatty acids that have double-bonds and single bonds separated by a methylene unit (−CH2−). Because of the fluorescent properties conferred by the alternating double bonds, α-parinaric acid is commonly used as a molecular probe in the study of biomembranes.
Triglyceride lipases are a family of lipolytic enzymes that hydrolyse ester linkages of triglycerides. Lipases are widely distributed in animals, plants and prokaryotes.
Electron nuclear double resonance (ENDOR) is a magnetic resonance technique for elucidating the molecular and electronic structure of paramagnetic species. The technique was first introduced to resolve interactions in electron paramagnetic resonance (EPR) spectra. It is currently practiced in a variety of modalities, mainly in the areas of biophysics and heterogeneous catalysis.
Ruthenium anti-cancer drugs are coordination complexes of ruthenium complexes that have anticancer properties. They promise to provide alternatives to platinum-based drugs for anticancer therapy. No ruthenium anti-cancer drug has been commercialized.
Paramagnetic nuclear magnetic resonance spectroscopy refers to nuclear magnetic resonance (NMR) spectroscopy of paramagnetic compounds. Although most NMR measurements are conducted on diamagnetic compounds, paramagnetic samples are also amenable to analysis and give rise to special effects indicated by a wide chemical shift range and broadened signals. Paramagnetism diminishes the resolution of an NMR spectrum to the extent that coupling is rarely resolved. Nonetheless spectra of paramagnetic compounds provide insight into the bonding and structure of the sample. For example, the broadening of signals is compensated in part by the wide chemical shift range (often 200 ppm in 1H NMR). Since paramagnetism leads to shorter relaxation times (T1), the rate of spectral acquisition can be high.
Aptamers, single-stranded RNA and DNA sequences, bind to an analyte and change their conformation. They function as nucleic acids selectively binding molecules such as proteins, bacteria cells, metal ions, etc. Aptamers can be developed to have precise specificity to bind to a desired target. Aptamers change conformation upon binding, altering the electrochemical properties which can be measured. The Systematic Evolution of Ligands by Exponential Enrichment (SELEX) process generates aptamers. Electrochemical aptamer-based (E-AB) biosensors is a device that takes advantage of the electrochemical and biological properties of aptamers to take real time, in vivo measurements.
David Collison is a British chemist and a Professor in the Department of Chemistry at The University of Manchester. His research in general is based on inorganic chemistry and magnetochemistry, specifically on coordination chemistry, electron paramagnetic resonance spectroscopy and f-block chemistry.
Electron resonance imaging (ERI) is a preclinical imaging method, together with positron emission tomography (PET), computed tomography scan, magnetic resonance imaging (MRI), and other techniques. ERI is dedicated to imaging small laboratory animals and its unique feature is the ability to detect free radicals. This technique could also be used for other purposes such as material science, quality of food, etc.
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