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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 13015

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Special Issue Editors

Prof. Dr. Dmitry B. Zorov

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Guest Editor

A.N.Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow 119991, Russia
Interests: mitochondria; bioenergetics; redox; reactive opxygen species; ATP synthase; respiration; phosphorylation; membranes; kidney; brain; cell death; protection
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Prof. Dr. Vitaliy Borisov

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Guest Editor

Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Leninskie Gory, Moscow 119991, Russia
Interests: biochemistry; molecular mechanisms of enzyme action; molecular bioenergetics; membrane proteins; respiratory chains; terminal oxidases; cytochromes
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Prof. Dr. Andrey V. Golovin

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Guest Editor

Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119234 Moscow, Russia
Interests: structural bioinformatics; biopolymer structure and dynamics; computational enzymology; Zn function in proteins

Dr. Alexander O. Chizhov

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Guest Editor

N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Science, Leninsky pr. 47, 119991 Moscow, Russia
Interests: carbohydrate analysis; carbohydrate structure; glycoconjugates; mass spectrometry; electrospray ionization; MALDI; fragmentation of ions; activation of ions; sample preparation
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Special Issue Information

Dear Colleagues,

This Regional Project aims to collect high-quality research articles, review articles, and communications on all aspects of biochemistry from Russia. We encourage the submission of manuscripts that provide novel and mechanistic insights and papers that report significant advances in the fields.

The areas of interest for the regional collection include but are not limited to topics such as:

Molecular Bioenergetics；
Cellular function and structure;
Cell signaling;
Cell Metabolism;
Proteostasis and disease;
Protein biosynthesis;
Gene and protein structure and expression;
Cancer pathology and biology;
Aging biology and age-related diseases;
Drugs and pharmaceutics;
Post-translational modifications in health and disease;
New approaches in the management of hypoxic tumors;
Cancer metabolism and molecular genetics;
Enzymology and structural biology;
Metalloenzymes;
Enzyme activation and inhibition;
Targeting human enzymes involved in tumorigenesis;
Function and structure of lipid membrane;
Drug distribution and drug resistance;
Protein interactions and functional nucleic acids;
Epigenetic and genetic regulatory mechanisms;
Lipid metabolism;
Role of intestinal microbes in diseases and human health;
Characterization and development of small molecules for targeting metabolic pathways essential for the life cycle of human pathogens;
Neurochemistry;
Glycobiology;
Immunology;
Stem cell biology;
Regenerative therapy;
Membrane channels and transporters;
Membrane receptors.

Prof. Dr. Dmitry B. Zorov
Prof. Dr. Vitaliy Borisov
Prof. Dr. Andrey V. Golovin
Dr. Alexander O. Chizhov
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

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Published Papers (5 papers)

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Research

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14 pages, 2796 KiB

Open AccessArticle

Simple In Vitro ¹⁸O Labeling for Improved Mass Spectrometry-Based Drug Metabolites Identification: Deep Drug Metabolism Study

by Boris Tupertsev, Sergey Osipenko, Albert Kireev, Eugene Nikolaev and Yury Kostyukevich

Int. J. Mol. Sci. 2023, 24(5), 4569; https://doi.org/10.3390/ijms24054569 - 26 Feb 2023

Cited by 2 | Viewed by 1694

Abstract

The identification of drug metabolites formed with different in vitro systems by HPLC-MS is a standard step in preclinical research. In vitro systems allow modeling of real metabolic pathways of a drug candidate. Despite the emergence of various software and databases, identification of compounds is still a complex task. Measurement of the accurate mass, correlation of chromatographic retention times and fragmentation spectra are often insufficient for identification of compounds especially in the absence of reference materials. Metabolites can “slip under the nose”, since it is often not possible to reliably confirm that a signal belongs to a metabolite and not to other compounds in complex systems. Isotope labeling has proved to be a tool that aids in small molecule identification. The introduction of heavy isotopes is done with isotope exchange reactions or with complicated synthetic schemes. Here, we present an approach based on the biocatalytic insertion of oxygen-18 isotope under the action of liver microsomes enzymes in the presence of ¹⁸O₂. Using the local anesthetic bupivacaine as an example, more than 20 previously unknown metabolites were reliably discovered and annotated in the absence of the reference materials. In combination with high-resolution mass spectrometry and modern methods of mass spectrometric metabolism data processing, we demonstrated the ability of the proposed approach to increase the degree of confidence in interpretating metabolism data. Full article

(This article belongs to the Special Issue State-of-the-Art Biochemistry in Russia)

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19 pages, 4328 KiB

Open AccessArticle

Nucleoside Analogs That Inhibit SARS-CoV-2 Replication by Blocking Interaction of Virus Polymerase with RNA

by Elena Matyugina, Ivan Petushkov, Sergei Surzhikov, Vasily Kezin, Anna Maslova, Olga Ivanova, Olga Smirnova, Ilya Kirillov, Irina Fedyakina, Andrey Kulbachinskiy, Sergey Kochetkov and Anastasia Khandazhinskaya

Int. J. Mol. Sci. 2023, 24(4), 3361; https://doi.org/10.3390/ijms24043361 - 8 Feb 2023

Cited by 3 | Viewed by 2416

Abstract

The SARS-CoV-2 betacoronavirus pandemic has claimed more than 6.5 million lives and, despite the development and use of COVID-19 vaccines, remains a major global public health problem. The development of specific drugs for the treatment of this disease remains a very urgent task. In the context of a repurposing strategy, we previously screened a library of nucleoside analogs showing different types of biological activity against the SARS-CoV-2 virus. The screening revealed compounds capable of inhibiting the reproduction of SARS-CoV-2 with EC₅₀ values in the range of 20–50 µM. Here we present the design and synthesis of various analogs of the leader compounds, the evaluation of their cytotoxicity and antiviral activity against SARS-CoV-2 in cell cultures, as well as experimental data on RNA-dependent RNA polymerase inhibition. Several compounds have been shown to prevent the interaction between the SARS-CoV-2 RNA-dependent RNA polymerase and the RNA substrate, likely inhibiting virus replication. Three of the synthesized compounds have also been shown to inhibit influenza virus. The structures of these compounds can be used for further optimization in order to develop an antiviral drug. Full article

(This article belongs to the Special Issue State-of-the-Art Biochemistry in Russia)

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Review

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19 pages, 2492 KiB

Open AccessReview

Six Functions of Respiration: Isn’t It Time to Take Control over ROS Production in Mitochondria, and Aging Along with It?

by Vladimir P. Skulachev, Mikhail Yu. Vyssokikh, Boris V. Chernyak, Armen Y. Mulkidjanian, Maxim V. Skulachev, Gregory A. Shilovsky, Konstantin G. Lyamzaev, Vitaliy B. Borisov, Fedor F. Severin and Victor A. Sadovnichii

Int. J. Mol. Sci. 2023, 24(16), 12540; https://doi.org/10.3390/ijms241612540 - 8 Aug 2023

Cited by 13 | Viewed by 2835

Abstract

Cellular respiration is associated with at least six distinct but intertwined biological functions. (1) biosynthesis of ATP from ADP and inorganic phosphate, (2) consumption of respiratory substrates, (3) support of membrane transport, (4) conversion of respiratory energy to heat, (5) removal of oxygen to prevent oxidative damage, and (6) generation of reactive oxygen species (ROS) as signaling molecules. Here we focus on function #6, which helps the organism control its mitochondria. The ROS bursts typically occur when the mitochondrial membrane potential (MMP) becomes too high, e.g., due to mitochondrial malfunction, leading to cardiolipin (CL) oxidation. Depending on the intensity of CL damage, specific programs for the elimination of damaged mitochondria (mitophagy), whole cells (apoptosis), or organisms (phenoptosis) can be activated. In particular, we consider those mechanisms that suppress ROS generation by enabling ATP synthesis at low MMP levels. We discuss evidence that the mild depolarization mechanism of direct ATP/ADP exchange across mammalian inner and outer mitochondrial membranes weakens with age. We review recent data showing that by protecting CL from oxidation, mitochondria-targeted antioxidants decrease lethality in response to many potentially deadly shock insults. Thus, targeting ROS- and CL-dependent pathways may prevent acute mortality and, hopefully, slow aging. Full article

(This article belongs to the Special Issue State-of-the-Art Biochemistry in Russia)

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17 pages, 3847 KiB

Open AccessReview

Interaction of Terminal Oxidases with Amphipathic Molecules

by Natalia V. Azarkina, Vitaliy B. Borisov, Ilya P. Oleynikov, Roman V. Sudakov and Tatiana V. Vygodina

Int. J. Mol. Sci. 2023, 24(7), 6428; https://doi.org/10.3390/ijms24076428 - 29 Mar 2023

Cited by 3 | Viewed by 1540

Abstract

The review focuses on recent advances regarding the effects of natural and artificial amphipathic compounds on terminal oxidases. Terminal oxidases are fascinating biomolecular devices which couple the oxidation of respiratory substrates with generation of a proton motive force used by the cell for ATP production and other needs. The role of endogenous lipids in the enzyme structure and function is highlighted. The main regularities of the interaction between the most popular detergents and terminal oxidases of various types are described. A hypothesis about the physiological regulation of mitochondrial-type enzymes by lipid-soluble ligands is considered. Full article

(This article belongs to the Special Issue State-of-the-Art Biochemistry in Russia)

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17 pages, 1287 KiB

Open AccessReview

Perspectives for the Use of Fucoidans in Clinical Oncology

by Mikhail V. Kiselevskiy, Natalia Yu. Anisimova, Nadezhda E. Ustyuzhanina, Dmitry Z. Vinnitskiy, Alexandra I. Tokatly, Vera V. Reshetnikova, Irina O. Chikileva, Irina Zh. Shubina, Kirill I. Kirgizov and Nikolay E. Nifantiev

Int. J. Mol. Sci. 2022, 23(19), 11821; https://doi.org/10.3390/ijms231911821 - 5 Oct 2022

Cited by 17 | Viewed by 3468

Abstract

Fucoidans are natural sulfated polysaccharides that have a wide range of biological functions and are regarded as promising antitumor agents. The activity of various fucoidans and their derivatives has been demonstrated in vitro on tumor cells of different histogenesis and in experiments on mice with grafted tumors. However, these experimental models showed low levels of antitumor activity and clinical trials did not prove that this class of compounds could serve as antitumor drugs. Nevertheless, the anti-inflammatory, antiangiogenic, immunostimulating, and anticoagulant properties of fucoidans, as well as their ability to stimulate hematopoiesis during cytostatic-based antitumor therapy, suggest that effective fucoidan-based drugs could be designed for the supportive care and symptomatic therapy of cancer patients. The use of fucoidans in cancer patients after chemotherapy and radiation therapy might promote the rapid improvement of hematopoiesis, while their anti-inflammatory, immunomodulatory, and anticoagulant effects have the potential to improve the quality of life of patients with advanced cancer. Full article

(This article belongs to the Special Issue State-of-the-Art Biochemistry in Russia)

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