Guanidinium Group Research Articles

What the Fork? A Structural Bioinformatics Approach to Decipher Patterns in Arginine-Fork Mediated RNA Recognition

The amino acid arginine can recognize RNA with striking diversity and a level of specificity that forms the basis of numerous essential biological interactions. Nearly 30 years ago, Frankel and co-workers postulated a theoretical model for Tat-mediated recognition of HIV-1 TAR in which a specific arginine residue forms four hydrogen bonds with two nearby phosphates to yield a two-pronged readout interaction.1 This ‘arginine fork’ model was posited to exist widely in RNA-protein recognition but languished without a substantial structural database. Fortunately, a collection of high-resolution RNA-protein structures is now available, providing a structurally rich landscape to systematically evaluate the fork hypothesis. indeed, a variation of the arginine fork was observed recently that featured: (i) a single arginine forming hydrogen bonds to the phosphate backbone and the Hoogsteen edge of a guanine nucleobase;and (ii) simultaneous engagement of the arginine guanidinium group in cation-π stacks with flanking nucleobases. Using this experimentally based framework for arginine-mediated base-specific readout, we conducted a structural bioinformatic search of an RNA-protein library of crystal structures retrieved from the protein data bank. Filtering was applied to satisfy the two arginine-fork criteria above. The results revealed four distinct classes of arginine-forks. We report arginine rotamer and RNA backbone conformation (suite) analysis of the arginine-fork interfaces. Additionally, we also present a practical application of the arginine-fork, which was used to improve NMR modeling of the HIV-1 Tat-TAR structure, and to correct atypical arginine-guanine interactions. Overall, our results can improve modeling of RNA-protein interfaces and provide insight into arginine-mediated recognition of specific RNA sequences, which is relevant to drug discovery. 1. Calnan, Barbara J., et al. Science (1991): 1167-1171. 2. Belashov, Ivan A., et al. Nucleic acids research 46.13 (2018): 6401-6415.

Arginine Methylation Regulates Ribosome CAR Function.

The ribosome CAR interaction surface is hypothesized to provide a layer of translation regulation through hydrogen-bonding to the +1 mRNA codon that is next to enter the ribosome A site during translocation. The CAR surface consists of three residues, 16S/18S rRNA C1054, A1196 (E. coli 16S numbering), and R146 of yeast ribosomal protein Rps3. R146 can be methylated by the Sfm1 methyltransferase which is downregulated in stressed cells. Through molecular dynamics analysis, we show here that methylation of R146 compromises the integrity of CAR by reducing the cation-pi stacking of the R146 guanidinium group with A1196, leading to reduced CAR hydrogen-bonding with the +1 codon. We propose that ribosomes assembled under stressed conditions have unmethylated R146, resulting in elevated CAR/+1 codon interactions, which tunes translation levels in response to the altered cellular context.

Comparative Study of Interactions between Human cGAS and Inhibitors: Insights from Molecular Dynamics and MM/PBSA Studies.

Recent studies have identified cyclic GMP-AMP synthase (cGAS) as an important target for treating autoimmune diseases, and several inhibitors of human cGAS (hcGAS) and their structures in complexation with hcGAS have been reported. However, the mechanisms via which these inhibitors interact with hcGAS are not completely understood. Here, we aimed to assess the performance of molecular mechanics/Poisson–Boltzmann solvent-accessible surface area (MM/PBSA) in evaluating the binding affinity of various hcGAS inhibitors and to elucidate their detailed interactions with hcGAS from an energetic viewpoint. Using molecular dynamics (MD) simulation and MM/PBSA approaches, the estimated free energies were in good agreement with the experimental ones, with a Pearson’s correlation coefficient and Spearman’s rank coefficient of 0.67 and 0.46, respectively. In per-residue energy decomposition analysis, four residues, K362, R376, Y436, and K439 in hcGAS were found to contribute significantly to the binding with inhibitors via hydrogen bonding, salt bridges, and various π interactions, such as π· · ·π stacking, cation· · ·π, hydroxyl· · ·π, and alkyl· · ·π interactions. In addition, we discussed other key interactions between specific residues and ligands, in particular, between H363 and JUJ, F379 and 9BY, and H437 and 8ZM. The sandwiched structures of the inhibitor bound to the guanidinium group of R376 and the phenyl ring of Y436 were also consistent with the experimental data. The results indicated that MM/PBSA in combination with other virtual screening methods, could be a reliable approach to discover new hcGAS inhibitors and thus is valuable for potential treatments of cGAS-dependent inflammatory diseases.

Targeting mechanism for SARS-CoV-2 in silico: interaction and key groups of TMPRSS2 toward four potential drugs.

The global dissemination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has seriously endangered human health. The number of confirmed cases is still increasing; however, treatment options are limited. Transmembrane protease serine 2 (TMPRSS2), as a key protease that primes the binding of SARS-CoV-2 spike protein and angiotensin-converting enzyme 2 (ACE2), has become an attractive target and received widespread attention. Thus, four potential drugs (bromhexine, camostat, gabexate, and nafamostat) were used to explore the mechanism of binding with TMPRSS2 in this work. A 65 ns molecular dynamics simulation was performed three times for each drug-TMPRSS2 system for reliable energy calculation and conformational analysis, of which the simulations of nafamostat-TMPRSS2 systems were further extended to 150 ns three times due to the discovery of two binding modes. Through the results of calculating binding free energy by nine methods, the binding affinity of camostat, gabexate, and nafamostat to TMPRSS2 showed great advantages compared with bromhexine, where the nafamostat was surprisingly found to present two reasonable binding conformations (forward and reverse directions). Two negatively charged amino acids (Asp435 and Glu299) can clamp the two positively charged groups (guanidinium group and amidinium group) in either forward or reverse fashion, and the forward one is more stable than the reverse. In addition, compared with gabexate, the dimethylamino group in camostat forms more van der Waals interactions with surrounding hot-spots His296 and Val280, resulting in a stronger affinity to TMPRSS2. For bromhexine, multiple binding sites are displayed in the binding pocket due to its small molecular structure, and van der Waals interactions play the dominant role in the binding process. In particular, six typical hot-spots were identified in the last three serine protease inhibitor systems, i.e., Asp435, Ser436, Gln438, Trp461, Ser463, and Gly464. The guanidinium groups of the drugs have powerful interactions with adjacent residues due to the formation of more hydrogen bonds, suggesting that this may be the critical site for drug design against TMPRSS2. This work provides valuable molecular insight into these four drug-TMPRSS2 binding mechanisms and is helpful for designing and screening drugs targeting TMPRSS2.

Calixarene-decorated liposomes for intracellular cargo delivery.

Amphiphilic calix[4]arenes, functionalized with guanidinium groups, are used to decorate the outer surface of liposomes and significantly improve the cellular uptake of a cargo compared to plain liposomes. The improved uptake is elicited and mediated by the interaction between the cationic polar heads of the macrocycle units embedded in the liposome bilayer and anionic heparan-sulfate proteoglycans surrounding the exterior of cells.

Enzyme Multifunctionality by Control of Substrate Positioning Within the Catalytic Cycle-A QM/MM Study of Clavaminic Acid Synthase.

Clavaminic acid synthase from Streptomyces clavuligerus is an FeII /2-oxoglutarate-dependent dioxygenase, crucial for the biosynthesis of the β-lactamase inhibitor clavulanic acid. It catalyses three consecutive oxidative reactions, that is, hydroxylation, cyclisation and desaturation, in a single binding cavity. As follows from the results of this QM/MM study, CAS versatility and selectivity depends on the binding cavity, which interplays differently with the substrate for each reaction. The enzyme-substrate interactions affect the substrate's ability to re-position during the reaction, either constraining it in its primary position, which impedes processes other than oxygen rebound, or allowing change, which facilitates desaturation. This differential effect originates from two aspartate residues, which strongly interact with the guanidine group of the hydroxylation substrate and stabilise the orientation of the molecule. These residues interact less effectively with the smaller amine group of the desaturation substrate(s), aiding their re-positioning and the subsequent formation of a double bond.

MODIFICATION OF CHITOSAN BY THIOUREA DIOXIDE

Thiourea dioxide (TDO, aminoiminomethanesulfinic acid, formamidinesulfinic acid) was used for the chemical modification of chitosan. The interaction of TDO with chitosan in the presence of alkali results in the guanidinylated chitosan, the substitution degree is 0.25-0.27 and does not depend largely on molar ratio of thiourea dioxide to chitosan. The structure of modified chitosan has been proved using UV and IR spectroscopy as well as elemental analysis. It is shown that modification of chitosan proceeds under mild conditions. Contrary to chitosan, its guanidinylated derivative has biocidal properties against Gram-positive and Gram-negative bacteria in the aqueous solutions close to neutral (pH 6.2). It can be explained by the partial substitution of amino groups by guanidine groups existing predominantly in the protonated form in the neutral aqueous solutions. The system thiourea dioxide-hydrogen peroxide was used for the oxidative modification of chitosan. It is shown that thiourea dioxide and hydrogen peroxide separately do not oxidize chitosan but in the presence of their mixture the formation of carboxylic groups in chitosan has been observed. The quantity of carboxylic groups in the modified and native chitosan has been determined by the titration with sodium hydroxide. The presence of carboxylic groups has been proved also using IR spectroscopy. It is shown that the quantity of carboxylic groups increases with the increase of the ratio [TDO]/[chitosan].

Synthesis and Anticancer Evaluation of Benzimidazole Derivatives Having Norbornene/Dibenzobarrelene Skeletons and Different Functional Groups

AbstractTwo different anhydrides having norbornene and dibenzobarrelene skeletons were synthesized from Diels‐Alder cycloaddition reactions using dienes such as anthracene and cyclopentadiene, and dienophiles like maleic acid and maleic anhydride. New benzimidazole derivatives bearing carboxamide, guanidine, and cyclic imide functional groups were obtained from these anhydrides. The compounds were investigated for their effects on MDA‐MB‐231 (Human breast cancer), A549 (Lung cancer), Ovcar3 (Human Ovarian cancer), and Panc1 (human pancreas cancer) cell lines using the MTT assay test. Compounds4–8demonstrated critical cytotoxic action against all cell lines.

The RNA Polymerase α Subunit Recognizes the DNA Shape of the Upstream Promoter Element.

We demonstrate here that the α subunit C-terminal domain of Escherichia coli RNA polymerase (αCTD) recognizes the upstream promoter (UP) DNA element via its characteristic minor groove shape and electrostatic potential. In two compositionally distinct crystallized assemblies, a pair of αCTD subunits bind in tandem to the UP element consensus A-tract that is 6 bp in length (A6-tract), each with their arginine 265 guanidinium group inserted into the minor groove. The A6-tract minor groove is significantly narrowed in these crystal structures, as well as in computationally predicted structures of free and bound DNA duplexes derived by Monte Carlo and molecular dynamics simulations, respectively. The negative electrostatic potential of free A6-tract DNA is substantially enhanced compared to that of generic DNA. Shortening the A-tract by 1 bp is shown to "knock out" binding of the second αCTD through widening of the minor groove. Furthermore, in computationally derived structures with arginine 265 mutated to alanine in either αCTD, either with or without the "knockout" DNA mutation, contact with the DNA is perturbed, highlighting the importance of arginine 265 in achieving αCTD-DNA binding. These results demonstrate that the importance of the DNA shape in sequence-dependent recognition of DNA by RNA polymerase is comparable to that of certain transcription factors.

Arginine Forks Are a Widespread Motif to Recognize Phosphate Backbones and Guanine Nucleobases in the RNA Major Groove.

RNA recognition by proteins is central to biology. Here we demonstrate the existence of a recurrent structural motif, the "arginine fork", that codifies arginine readout of cognate backbone and guanine nucleobase interactions in a variety of protein-RNA complexes derived from viruses, metabolic enzymes, and ribosomes. Nearly 30 years ago, a theoretical arginine fork model was posited to account for the specificity between the HIV-1 Tat protein and TAR RNA. This model predicted that a single arginine should form four complementary contacts with nearby phosphates, yielding a two-pronged backbone readout. Recent high-resolution structures of TAR-protein complexes have unveiled new details, including (i) arginine interactions with the phosphate backbone and the major-groove edge of guanine and (ii) simultaneous cation-π contacts between the guanidinium group and flanking nucleobases. These findings prompted us to search for arginine forks within experimental protein-RNA structures retrieved from the Protein Data Bank. The results revealed four distinct classes of arginine forks that we have defined using a rigorous but flexible nomenclature. Examples are presented in the context of ribosomal and nonribosomal interfaces with analysis of arginine dihedral angles and structural (suite) classification of RNA targets. When arginine fork chemical recognition principles were applied to existing structures with unusual arginine-guanine recognition, we found that the arginine fork geometry was more consistent with the experimental data, suggesting the utility of fork classifications to improve structural models. Software to analyze arginine-RNA interactions has been made available to the community.

Design, synthesis biological activity, and docking of novel fluopyram derivatives containing guanidine group

Succinate dehydrogenase (SDH), a crucial bridge enzyme between the respiratory electron transfer chain and tricarboxylic acid (or Krebs) cycle, has been identified as an ideal target for the development of effective fungicide. In this study, a series of 24 novel SDH inhibitors (SDHIs) were designed, synthesized, and characterized by 1H NMR, 13C NMR, and HRMS. In vitro fungicidal activity experiments, most of the compounds exhibited broad-spectrum antifungal activities against five plant pathogenic fungi. Compounds 9j and 9k showed excellent activities against Pythium aphanidermatum with EC50 values of 9.93 mg/L and 10.50 mg/L, respectively, which were superior to the lead compound Fluopyram with an EC50 value of 19.10 mg/L. Furthermore, the toxicity of these compounds was also tested against Meloidogyne incognita J2 nematodes. The results indicated that compound 9x exhibited moderate nematicidal activity (LC50/48 h = 71.02 mg/L). Molecular docking showed that novel guanidine amide of 9j formed hydrogen bonds with crucial residues, which was crucial to the binding of an inhibitor and SDH. This present work indicates that these derivatives may serve as novel potential fungicides targeting SDH.

Gas-Phase Fragmentation of ADP-Ribosylated Peptides: Arginine-Specific Side-Chain Losses and Their Implication in Database Searches.

ADP-ribosylation is a reversible post-translational modification of proteins that has been linked to many biological processes. The identification of ADP-ribosylated proteins and particularly of their acceptor amino acids remains a major challenge. The attachment sites of the modification are difficult to localize by mass spectrometry (MS) because of the labile nature of the linkage and the complex fragmentation pattern of the ADP-ribose in MS/MS experiments. In this study we performed a comprehensive analysis of higher-energy collisional dissociation (HCD) spectra acquired from ADP-ribosylated peptides which were modified on arginine, serine, glutamic acid, aspartic acid, tyrosine, or lysine residues. In addition to the fragmentation of the peptide backbone, various cleavages of the ADP-ribosylated amino acid side chains were investigated. We focused on gas-phase fragmentations that were specific either to ADP-ribosylated arginine or to ADP-ribosylated serine and other O-linked ADP-ribosylations. The O-glycosidic linkage between ADP-ribose and serine, glutamic acid, or aspartic acid was the major cleavage site, making localization of these modification sites difficult. In contrast, the bond between ADP-ribose and arginine was relatively stable. The main cleavage site was the inner bond of the guanidine group, which resulted in the formation of ADP-ribosylated carbodiimide and of ornithine in place of modified arginine. Taking peptide fragment ions resulting from this specific cleavage into account, a considerably larger number of peptides containing ADP-ribosylated arginine were identified in database searches. Furthermore, the presence of diagnostic ions and of losses of fragments from peptide ions allowed us, in most cases, to distinguish between ADP-ribosylated arginine and serine residues.

Guanidinium-Incorporated Micelleplexes for Low Toxic and Efficient siRNA Delivery

Small interfering RNA (siRNA)-based therapy has emerged as a powerful therapeutic tool due to its target-specific gene silencing. However, the therapeutic efficacy has been limited by poor cellular uptake, and therefore delivery vehicles are required to improve the cellular uptake. Herein, guanidinium-incorporated polyether-based block copolyelectrolytes were developed for improved cellular uptake and consequently increased gene silencing efficiency. Guanidinium-functionalized poly(ethylene oxide-b-allyl glycidyl ether) (G-PEO-PAGE) were prepared by living anionic ring opening polymerization of allyl glycidyl ether and post-modification to introduce guanidinium groups. G-PEO-PAGE provides efficient complexation with siRNA due to highly cationic charges of the guanidinium groups at physiological pH, resulting in significantly improved cellular uptake of siRNA and consequently increased gene silencing efficiency. In addition, G-PEO-PAGE showed significantly lower cytotoxicity compared to branched polyethylenimine as a commercial counterpart. This study demonstrates that guanidinium-incorporated block copolyelectrolytes have a great potential for efficient and low toxic siRNA delivery.

Allele-Specific PCR for KRAS Mutation Detection Using Phosphoryl Guanidine Modified Primers.

Establishing the Kirsten rat sarcoma (KRAS) mutational status is essential in terms of managing patients with various types of cancer. Allele-specific real-time polymerase chain reaction (AS-PCR) is a widely used method for somatic mutations detection. To improve the limited sensitivity and specificity, several blocking methods have been introduced in AS-PCR to block the amplification of wild-type templates. Herein, we used a novel modified oligonucleotide with internucleotide phosphates reshaped 1,3-dimethyl-2-imino-imidazolidine moieties (phosphoryl guanidine (PG) groups) as primers and blockers in the AS-PCR method. Four common KRAS mutations were chosen as a model to demonstrate the advantages of the PG primers and blockers utilizing a customized PCR protocol. The methods were evaluated on plasmid model systems providing a KRAS mutation detection limit of 20 copies of mutant DNA in a proportion as low as 0.1% of the total DNA, with excellent specificity. PG-modification can serve as the universal additional mismatch-like disturbance to increase the discrimination between wild-type and mutated DNA. Moreover, PG can serve to increase primer specificity by a synergetic effect with additional mismatch and would greatly facilitate medical research.

Catalysis of Hydrazone and Oxime Peptide Ligation by Arginine.

Hydrazone and oxime peptide ligations are catalyzed by arginine. The catalysis is assisted intramolecularly by the side-chain guanidinium group. Hydrazone ligation in the presence of arginine proceeds efficiently in phosphate buffer at neutral pH but is particularly powerful in bicarbonate/CO2 buffer. In addition to acting as a catalyst, arginine prevents the aggregation of proteins during ligation. With its dual properties as a nucleophilic catalyst and a protein aggregation inhibitor, arginine hydrochloride is a useful addition to the hydrazone/oxime ligation toolbox.

Novel guanidine compounds inhibit platelet-derived growth factor receptor alpha transcription and oligodendrocyte precursor cell proliferation.

Oligodendrocyte precursor cells (OPCs), also known as NG2 cells or polydendrocytes, are distributed widely throughout the developing and mature central nervous system. They remain proliferative throughout life and are an important source of myelinating cells in normal and demyelinating brain as well as a source of glioma, the most common type of primary brain tumor with a poor prognosis. OPC proliferation is dependent on signaling mediated by platelet-derived growth factor (PDGF) AA binding to its alpha receptor (PDGFRα). Here, we describe a group of structurally related compounds characterized by the presence of a basic guanidine group appended to an aromatic core that is effective in specifically repressing the transcription of Pdgfra but not the related beta receptor (Pdgfrb) in OPCs. These compounds specifically and dramatically reduced proliferation of OPCs but not that of astrocytes and did not affect signal transduction by PDGFRα. These findings suggest that the compounds could be further developed for potential use in combinatorial treatment strategies for neoplasms with dysregulated PDGFRα function.

An ESI Q-TOF study to understand the impact of arginine on CID MS/MS characteristics of polypeptides

To understand the importance of arginine (Arg) in influencing electrospray ionization (ESI) - collision induced dissociation (CID) tandem mass spectrometry (MS/MS) behavior of peptides of lengths > ∼ 25 amino acid residues (a.a.r.), we chose carbamidomethyl Insulin B-chain (30 a.a.r.), glucagon (29 a.a.r.) and melittin (26 a.a.r.) as the models for this investigation. Also, two smaller peptides: Angiotensin II (8 a.a.r.) and Bradykinin (9 a.a.r.) were studied for better comprehension of the interplay between the influence of Arg and peptide’s length. The motivation to study such longer peptides stems from middle-down proteomics, a recently emerging field encompassing investigations on proteolytic peptides longer than ∼ 25 a.a.r. CID MS/MS data of two different cases have been compared: (1) standard model peptides vs. chemically modified peptides, wherein sidechain guanidine group of Arg residues in these model peptides are selectively modified by 1,2-cyclohexanedione and phenylglyoxal; (2) standard model peptides vs. mutated model peptides, in which Arg residues in these model peptides are substituted by alanine (Ala) residues (Arg → Ala).Different types of stoichiometric products were obtained due to this chemical modification and each type of arginine-modified product was subjected to ESI CID MS/MS. The Arg → Ala mutated model peptides chosen for this study are: [R22A]-Insulin B-chain, [R17A & R18A]-Glucagon, [R22A & R24A]-Melittin and a shorter peptide: [R2A]-Angiotensin II. All experiments were performed in a quadrupole time-of-flight hybrid mass spectrometer, whereby CID (hexapole collision cell) was done by following fixed collision energy (CE) as well as ramped CE. Analysis of CID MS/MS spectra revealed that the sequence coverage of Arg → Ala mutated peptides was higher than the chemically modified peptides as well as their respective standard (unmodified) peptides. Examination of all the MS/MS data alluded that Arg has a greater influence on the CID MS/MS behavior of longer peptides, viz., lengths > 25 a.a.r., than the smaller peptides.

Chiral Cyclobutane-Containing Cell-Penetrating Peptides as Selective Vectors for Anti-Leishmania Drug Delivery Systems.

Two series of new hybrid γ/γ-peptides, γ-CC and γ-CT, formed by (1S,2R)-3-amino-2,2,dimethylcyclobutane-1-carboxylic acid joined in alternation to a Nα-functionalized cis- or trans-γ-amino-l-proline derivative, respectively, have been synthesized and evaluated as cell penetrating peptides (CPP) and as selective vectors for anti-Leishmania drug delivery systems (DDS). They lacked cytotoxicity on the tumoral human cell line HeLa with a moderate cell-uptake on these cells. In contrast, both γ-CC and γ-CT tetradecamers were microbicidal on the protozoan parasite Leishmania beyond 25 μM, with significant intracellular accumulation. They were conjugated to fluorescent doxorubicin (Dox) as a standard drug showing toxicity beyond 1 μM, while free Dox was not toxic. Intracellular accumulation was 2.5 higher than with Dox-TAT conjugate (TAT = transactivator of transcription, taken as a standard CPP). The conformational structure of the conjugates was approached both by circular dichroism spectroscopy and molecular dynamics simulations. Altogether, computational calculations predict that the drug-γ-peptide conjugates adopt conformations that bury the Dox moiety into a cavity of the folded peptide, while the positively charged guanidinium groups face the solvent. The favorable charge/hydrophobicity balance in these CPP improves the solubility of Dox in aqueous media, as well as translocation across cell membranes, making them promising candidates for DDS.

Crown ethers as shift reagents in peptide epimer differentiation \u2013conclusions from examination of ac-(H)FRW-NH2 petide sequences

Crown ethers with different ring sizes and substituents (18-crown-6, dibenzo-18-crown-6, dicyclohexano-18-crown-6, a chiral tetracarboxylic acid-18-crown-6 ether, dibenzo-21-crown-7, and dibenzo-30-crown-10) were evaluated as shift reagents to differentiate epimeric model peptides (tri-and tetrapeptides) using ion mobility mass spectrometry (IM-MS). The stable associates of peptide epimers with crown ethers were detected and examined using traveling-wave ion mobility time-of-flight mass spectrometer (Synapt G2-S HDMS) equipped with an electrospray ion source. The overall decrease of the epimer separation upon crown ether complexation was observed. The increase of the effectiveness of the microsolvation of a basic moiety - guanidine or ammonium group in the peptide had no or little effect on the epimer discrimination. Any increase of the epimer separation, which referred to the specific association mode between crown substituents and a given peptide sequence, was drastically reduced for the longer peptide sequence (tetrapeptide). The obtained results suggest that the application of the crown ethers as shift reagents in ion mobility mass spectrometry is limited to the formation of complexes differing in stoichiometry rather than it refers to a specific coordination mode between a crown ether and a peptide molecule.

Создание биоцидных препаратов «Тефлекс»: от синтеза нового полимера до линейки продукции. Часть 2. Исследование влияния препаратов «Тефлекс» на свойства цементных композитов

Повреждения строительных материалов, вызванные ро­стом и развитием на них бактерий и мицелиальных грибов представляют серьёзную опасность как для конструкций зданий и сооружений, так и для здоровья людей. Один из эффективных способов устранения данных негативных фак­торов - это введение в их состав биоцидных добавок.
 Приводятся результаты исследования свойств цементных композитов, содержащих в своем составе различные био­цидные препараты на основе гуанидиновой группировки (ПГМГ), которые выпускаются в РФ в промышленном масштабе под маркой «Тефлекс». При выполнении исследований рас­сматривались препараты марок: «Тефлекс Антиплесень», «Тефлекс Антисоль смывка», «Тефлекс Реставратор», «Тефлекс Защита для металла», «Тефлекс дезинфицирующий», «Тефлекс индустриальный». Показано, что применение биоцидных препаратов способствует снижению обрастаемости образцов цементных композитов мицелиальными грибами и проявле­ние у них грибостойких и фунгицидных свойств.
 С использованием метода рентгеноструктурного анализа выявлено, что при введении в составы соединений гуанидина изменяется количественное содержание минералов алита и белита. Исследованы цементные композиты, твердеющие как в нормальных температурно-влажностных условиях, так и подвергнутые термовлажностной обработке. Установлено, что введение всех рассмотренных добавок оказывает пластифи­цирующее действие и изменяет ряд других свойств. Прочность цементных композитов с добавками в количестве 3-5 мас. ч увеличивается. Приведены результаты исследования свойств композитов, наполненных кварцевыми порошками различной дисперсности и препаратом «Тефлекс». При этом наряду с одно­фракционными рассматривались многофракционные составы. Полученные результаты дают основание рекомендовать цемент­ные композиции, содержащие добавки на основе гуанидина, для использования в зданиях и сооружениях с биологическими средами. Приведены сведения о результатах использования цементных материалов и изделий в строительной отрасли.