Publications by authors named "Alexander A Stepanov"

11 Publications

  • Page 1 of 1

Molecular Portrait of an Athlete.

Diagnostics (Basel) 2021 Jun 15;11(6). Epub 2021 Jun 15.

Biobanking Group, Branch of Institute of Biomedical Chemistry "Scientific and Education Center", 109028 Moscow, Russia.

Sequencing of the human genome and further developments in "omics" technologies have opened up new possibilities in the study of molecular mechanisms underlying athletic performance. It is expected that molecular markers associated with the development and manifestation of physical qualities (speed, strength, endurance, agility, and flexibility) can be successfully used in the selection systems in sports. This includes the choice of sports specialization, optimization of the training process, and assessment of the current functional state of an athlete (such as overtraining). This review summarizes and analyzes the genomic, proteomic, and metabolomic studies conducted in the field of sports medicine.
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http://dx.doi.org/10.3390/diagnostics11061095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232626PMC
June 2021

Role of Chiral Configuration in the Photoinduced Interaction of D- and L-Tryptophan with Optical Isomers of Ketoprofen in Linked Systems.

Int J Mol Sci 2021 Jun 8;22(12). Epub 2021 Jun 8.

Voevodsky Institute of Chemical Kinetics and Combustion, 630090 Novosibirsk, Russia.

The study of the L- and D-amino acid properties in proteins and peptides has attracted considerable attention in recent years, as the replacement of even one L-amino acid by its D-analogue due to aging of the body is resulted in a number of pathological conditions, including Alzheimer's and Parkinson's diseases. A recent trend is using short model systems to study the peculiarities of proteins with D-amino acids. In this report, the comparison of the excited states quenching of L- and D-tryptophan (Trp) in a model donor-acceptor dyad with ()- and ()-ketoprofen (KP-Trp) was carried out by photochemically induced dynamic nuclear polarization (CIDNP) and fluorescence spectroscopy. Quenching of the Trp excited states, which occurs via two mechanisms: prevailing resonance energy transfer (RET) and electron transfer (ET), indeed demonstrates some peculiarities for all three studied configurations of the dyad: ()-, ()-, and ()-. Thus, the ET efficiency is identical for ()- and ()-enantiomers, while RET differs by 1.6 times. For ()-, the CIDNP coefficient is almost an order of magnitude greater than for ()- and ()-. To understand the source of this difference, hyperpolarization of ()-and ()- has been calculated using theory involving the electron dipole-dipole interaction in the secular equation.
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http://dx.doi.org/10.3390/ijms22126198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227724PMC
June 2021

Diversity of Plant Sterols Metabolism: The Impact on Human Health, Sport, and Accumulation of Contaminating Sterols.

Nutrients 2021 May 12;13(5). Epub 2021 May 12.

Institute of Biomedical Chemistry, Group of Biobanking, 10 Pogodinskaya Str., Bld. 8, 119121 Moscow, Russia.

The way of plant sterols transformation and their benefits for humans is still a question under the massive continuing revision. In fact, there are no receptors for binding with sterols in mammalians. However, possible biotransformation to steroids that can be catalyzed by gastro-intestinal microflora, microbial cells in prebiotics or cytochromes system were repeatedly reported. Some products of sterols metabolization are capable to imitate resident human steroids and compete with them for the binding with corresponding receptors, thus affecting endocrine balance and entire physiology condition. There are also tremendous reports about the natural origination of mammalian steroid hormones in plants and corresponding receptors for their binding. Some investigations and reports warn about anabolic effect of sterols, however, there are many researchers who are reluctant to believe in and have strong opposing arguments. We encounter plant sterols everywhere: in food, in pharmacy, in cosmetics, but still know little about their diverse properties and, hence, their exact impact on our life. Most of our knowledge is limited to their cholesterol-lowering influence and protective effect against cardiovascular disease. However, the world of plant sterols is significantly wider if we consider the thousands of publications released over the past 10 years.
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http://dx.doi.org/10.3390/nu13051623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150896PMC
May 2021

Mass Spectrometric Identification of Proteins Enhanced by the Atomic Force Microscopy Immobilization Surface.

Int J Mol Sci 2021 Jan 4;22(1). Epub 2021 Jan 4.

Institute of Biomedical Chemistry, 119121 Moscow, Russia.

An approach to highly-sensitive mass spectrometry detection of proteins after surface-enhanced concentrating has been elaborated. The approach is based on a combination of mass spectrometry and atomic force microscopy to detect target proteins. (1) Background: For this purpose, a technique for preliminary preparation of molecular relief surfaces formed as a result of a chemical or biospecific concentration of proteins from solution was developed and tested on several types of chip surfaces. (2) Methods: mass spectrometric identification of proteins using trailing detectors: ion trap, time of flight, orbital trap, and triple quadrupole. We used the electrospray type of ionization and matrix-assisted laser desorption/ionization. (3) Results: It is shown that when using locally functionalized atomically smooth surfaces, the sensitivity of the mass spectrometric method increases by two orders of magnitude as compared with measurements in solution. Conclusions: It has been demonstrated that the effective concentration of target proteins on specially prepared surfaces increases the concentration sensitivity of mass spectrometric detectors-time-of-flight, ion trap, triple quadrupole, and orbital ion trap in the concentration range from up to 10 M.
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http://dx.doi.org/10.3390/ijms22010431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795915PMC
January 2021

Pharmacogenetic Testing: A Tool for Personalized Drug Therapy Optimization.

Pharmaceutics 2020 Dec 19;12(12). Epub 2020 Dec 19.

Biobanking Group, Branch of Institute of Biomedical Chemistry "Scientific and Education Center", 109028 Moscow, Russia.

Pharmacogenomics is a study of how the genome background is associated with drug resistance and how therapy strategy can be modified for a certain person to achieve benefit. The pharmacogenomics (PGx) testing becomes of great opportunity for physicians to make the proper decision regarding each non-trivial patient that does not respond to therapy. Although pharmacogenomics has become of growing interest to the healthcare market during the past five to ten years the exact mechanisms linking the genetic polymorphisms and observable responses to drug therapy are not always clear. Therefore, the success of PGx testing depends on the physician's ability to understand the obtained results in a standardized way for each particular patient. The review aims to lead the reader through the general conception of PGx and related issues of PGx testing efficiency, personal data security, and health safety at a current clinical level.
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http://dx.doi.org/10.3390/pharmaceutics12121240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765968PMC
December 2020

Stereoselectivity of Electron and Energy Transfer in the Quenching of (/)-Ketoprofen-()-Tryptophan Dyad Excited State.

Int J Mol Sci 2020 Jul 28;21(15). Epub 2020 Jul 28.

Voevodsky Institute of Chemical Kinetics and Combustion SB RAS, 630090 Novosibirsk, Russia.

Photoinduced elementary processes in chiral linked systems, consisting of drugs and tryptophan (Trp) residues, attract considerable attention due to several aspects. First of all, these are models that allow one to trace the full and partial charge transfer underlying the binding of drugs to enzymes and receptors. On the other hand, Trp fluorescence is widely used to establish the structure and conformational mobility of proteins due to its high sensitivity to the microenvironment. Therefore, the study of mechanisms of Trp fluorescence quenching in various systems has both fundamental and practical interest. An analysis of the photo-chemically induced dynamic nuclear polarization (CIDNP) and Trp fluorescence quenching in (/)-ketoprofen-()-tryptophan ((/)-KP-()-Trp) dyad carried out in this work allowed us to trace the intramolecular reversible electron transfer (ET) and obtain evidence in favor of the resonance energy transfer (RET). The fraction of dyad's singlet excited state, quenched via ET, was shown to be 7.5 times greater for the (,)-diastereomer than for the (,) analog. At the same time, the ratio of the fluorescence quantum yields shows that quenching effectiveness of (,)-diastereomer to be 5.4 times lower than for the (,) analog. It means that the main mechanism of Trp fluorescence quenching in (/)-KP-()-Trp dyad is RET.
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http://dx.doi.org/10.3390/ijms21155370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432585PMC
July 2020

Revelation of Proteomic Indicators for Colorectal Cancer in Initial Stages of Development.

Molecules 2020 Jan 31;25(3). Epub 2020 Jan 31.

V.N. Orekhovich Institute of Biomedical Chemistry, 119121 Moscow, Russia.

Colorectal cancer (CRC) at a current clinical level is still hardly diagnosed, especially with regard to nascent tumors, which are typically asymptotic. Searching for reliable biomarkers of early diagnosis is an extremely essential task. Identification of specific post-translational modifications (PTM) may also significantly improve net benefits and tailor the process of CRC recognition. We examined depleted plasma samples obtained from 41 healthy volunteers and 28 patients with CRC at different stages to conduct comparative proteome-scaled analysis. The main goal of the study was to establish a constellation of protein markers in combination with their PTMs and semi-quantitative ratios that may support and realize the distinction of CRC until the disease has a poor clinical manifestation. Proteomic analysis revealed 119 and 166 proteins for patients in stages I-II and III-IV, correspondingly. Plenty of proteins (44 proteins) reflected conditions of the immune response, lipid metabolism, and response to stress, but only a small portion of them were significant ( < 0.01) for distinguishing stages I-II of CRC. Among them, some cytokines (Clusterin (CLU), C4b-binding protein (C4BP), and CD59 glycoprotein (CD59), etc.) were the most prominent and the lectin pathway was specifically enhanced in patients with CRC. Significant alterations in Inter-alpha-trypsin inhibitor heavy chains (ITIH1, ITIH2, ITIH3, and ITIH4) levels were also observed due to their implication in tumor growth and the malignancy process. Other markers (Alpha-1-acid glycoprotein 2 (ORM2), Alpha-1B-glycoprotein (A1BG), Haptoglobin (HP), and Leucine-rich alpha-2-glycoprotein (LRG1), etc.) were found to create an ambiguous core involved in cancer development but also to exactly promote tumor progression in the early stages. Additionally, we identified post-translational modifications, which according to the literature are associated with the development of colorectal cancer, including kininogen 1 protein (T327-p), alpha-2-HS-glycoprotein (S138-p) and newly identified PTMs, i.e., vitamin D-binding protein (K75-ac and K370-ac) and plasma protease C1 inhibitor (Y294-p), which may also contribute and negatively impact on CRC progression. The contribution of cytokines and proteins of the extracellular matrix is the most significant factor in CRC development in the early stages. This can be concluded since tumor growth is tightly associated with chronic aseptic inflammation and concatenated malignancy related to loss of extracellular matrix stability. Due attention should be paid to Apolipoprotein E (APOE), Apolipoprotein C1 (APOC1), and Apolipoprotein B-100 (APOB) because of their impact on the malfunction of DNA repair and their capability to regulate mTOR and PI3K pathways. The contribution of the observed PTMs is still equivocal, but a significant decrease in the likelihood between modified and native proteins was not detected confidently.
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http://dx.doi.org/10.3390/molecules25030619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7036866PMC
January 2020

Pilot data of serum proteins from children with autism spectrum disorders.

Data Brief 2019 Dec 25;27:104558. Epub 2019 Sep 25.

Institute of Biomedical Chemistry, Russia.

Protein profiles of 13 serum samples from children with autism spectrum disorders (ASD) and 11 serum samples from healthy volunteers was obtained using panoramic ultra-high resolution mass spectrometry. The analysis of measurements was performed using the proteomics search engine. We identified a group of 74 proteins which we term a "protein fingerprint" specific for serum samples collected from children with autism. Components of the protein fingerprint are involved in hemostasis maintenance including biological regulation, the response to stimulus, regulation of metabolism, and proteins of the immune system.
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http://dx.doi.org/10.1016/j.dib.2019.104558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817683PMC
December 2019

Immuno-MALDI MS dataset for improved detection of HCVcoreAg in sera.

Data Brief 2019 Aug 8;25:104240. Epub 2019 Jul 8.

Institute of Biomedical Chemistry, Pogodinskaya St. 10, Moscow, 119121 Russia.

Complicated and large-scale challenge the contemporary biomedical community faces are development of highly-sensitive analytical methods for detection of protein markers associated with development of pathogenic mechanisms [2]. The atomic force microscopy (AFM) method in combination with specific fishing is unique among other analytical protein detection approaches; it allows visualization and counting of single protein molecules [3-6]. The present dataset focus on mass spectrometry method for detection of human hepatitis C virus core antigen (HCV core Ag) taking into account the potential modification with cations in blood serum samples, using mica chips for the atomic force microscopy (AFM-chips). To conduct specific protein fishing, we used flat AFM-chips preliminary sensibilized with molecular probes - aptamers, which are single-stranded DNA sequences. In our study we used four types of aptamers up to 85 nucleotides specific against the target protein - HCVcoreAg [3,4]. Working (n = 19) and control (n = 11) AFM-chips with aptamers were preliminarily immobilized on the surface in four zones and incubated in blood serum samples (See Supplementary fig. 1). Analysis of MS data regarding modification of marker protein peptides with Na+, K+, K2Cl+, and Na2Cl + ions enables to enhance the reliability of target proteins detection in the serum thereby demonstrating a high diagnostic potential.
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http://dx.doi.org/10.1016/j.dib.2019.104240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6656991PMC
August 2019

Determination of Hyperfine Coupling Constants of Fluorinated Diphenylacetylene Radical Anions by Magnetic Field-Affected Reaction Yield Spectroscopy.

J Phys Chem A 2019 Jan 3;123(2):505-516. Epub 2019 Jan 3.

Institute of Chemical Kinetics and Combustion SB RAS , 3, Institutskaya Str. , 630090 Novosibirsk , Russian Federation.

Magnetic field-affected reaction yield (MARY) spectroscopy is a spin chemistry technique for detecting short-lived radical ions. Having sensitivity to transient species with lifetimes as short as nanoseconds, MARY spectroscopy usually does not provide detailed information on their magnetic resonance parameters, except for simple systems with equivalent magnetic nuclei. In this work, the radical anions of two fluorinated diphenylacetylene derivatives with nonequivalent magnetic nuclei and unknown hyperfine coupling constants ( A) were investigated by MARY spectroscopy. The MARY spectra were found to be resolved and have resonance lines in nonzero magnetic fields, which are determined by the A values. Simple relationships between the positions of resonance MARY lines and the A values were established from the analysis of the different Hamiltonian block contributions to the MARY spectrum. The obtained experimental A values are in agreement with the results of quantum chemical calculations at the density functional theory level.
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http://dx.doi.org/10.1021/acs.jpca.8b10306DOI Listing
January 2019

X-ray Generated Recombination Exciplexes of Substituted Diphenylacetylenes with Tertiary Amines: A Versatile Experimental Vehicle for Targeted Creation of Deep-Blue Electroluminescent Systems.

J Phys Chem A 2018 Feb 24;122(5):1235-1252. Epub 2018 Jan 24.

Institute of Chemical Kinetics and Combustion SB RAS , 3, Institutskaya Str., 630090 Novosibirsk, Russian Federation.

Customizable and technology-friendly functional materials are one of the mainstays of emerging organic electronics and optoelectronics. We show that recombination exciplexes of simple substituted diphenylacetylenes with tertiary amines can be a convenient source of tunable deep-blue emission with possible applications in organic electroluminescent systems. The optically inaccessible exciplexes were produced via recombination of radiation-generated radical ion pairs in alkane solution, which mimics charge transport and recombination in the active layer of practical organic light-emitting diodes in a simple solution-based experiment. Despite varying and rather poor intrinsic emission properties, diphenylacetylene and its prototypical methoxy (donor) or trifluoromethyl (acceptor) monosubstituted derivatives readily form recombination exciplexes with N,N-dimethylaniline and other tertiary amines that produce emission with maxima ranging from 385 to 435 nm. The position of emission band maximum linearly correlates with readily calculated gas-phase electron affinity of the corresponding diphenylacetylene, which can be used for fast computational prescreening of the candidate molecules, and various substituted diphenylacetylenes can be synthesized via relatively simple and universal cross-coupling reactions of Sonogashira and Castro. Together, the simple solution-based experiment, computationally cheap prescreening method, and universal synthetic strategy may open a very broad and chemically convenient class of compounds to obtain OLEDs and OLED-based multifunctional devices with tunable emission spectrum and high conversion efficiency that has yet not been seriously considered for these purposes.
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http://dx.doi.org/10.1021/acs.jpca.7b11634DOI Listing
February 2018
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