We describe a novel approach of reaction representation as a combination of two mixtures: a mixture of reactants and a mixture of products. In turn, each mixture can be encoded using an earlier reported approach involving simplex descriptors (SiRMS). The feature vector representing these two mixtures results from either concatenated product and reactant descriptors or the difference between descriptors of products and reactants. This reaction representation doesn't need an explicit labeling of a reaction center. The rigorous "product-out" cross-validation (CV) strategy has been suggested. Unlike the naïve "reaction-out" CV approach based on a random selection of items, the proposed one provides with more realistic estimation of prediction accuracy for reactions resulting in novel products. The new methodology has been applied to model rate constants of E2 reactions. It has been demonstrated that the use of the fragment control domain applicability approach significantly increases prediction accuracy of the models. The models obtained with new "mixture" approach performed better than those required either explicit (Condensed Graph of Reaction) or implicit (reaction fingerprints) reaction center labeling.

• Klíčová slova
• Chemical reactions, Condensed graph of reaction, Mixtures, Rate constant prediction, Reaction fingerprints, Simplex representation of molecular structure,
• MeSH
• kinetika MeSH
• kvantitativní vztahy mezi strukturou a aktivitou MeSH
• molekulární modely * MeSH
• molekulární struktura MeSH
• organické látky chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• organické látky MeSH

Chemical warfare agents are compounds of different chemical structures. Simple molecules such as chlorine as well as complex structures such as ricin belong to this group. Nerve agents, vesicants, incapacitating agents, blood agents, lung-damaging agents, riot-control agents and several toxins are among chemical warfare agents. Although the use of these compounds is strictly prohibited, the possible misuse by terrorist groups is a reality nowadays. Owing to this fact, knowledge of the basic properties of these substances is of a high importance. This chapter briefly introduces the separate groups of chemical warfare agents together with their members and the potential therapy that should be applied in case someone is intoxicated by these agents.

• MeSH
• antidota terapeutické užití   MeSH
• chemická válka * MeSH
• chemické bojové látky chemie   otrava   MeSH
• chemický terorismus MeSH
• lidé MeSH
• molekulární struktura MeSH
• otrava diagnóza   terapie   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• antidota MeSH
• chemické bojové látky MeSH

Lincomycin and its derivatives are antibiotics exhibiting biological activity against bacteria, especially Gram-positive ones, and also protozoans. Lincomycin and its semi-synthetic chlorinated derivative clindamycin are widely used in clinical practice. Both antibiotics are bacteriostatic, inhibiting protein synthesis in sensitive bacteria; however, at higher concentrations, they may be bactericidal. Clindamycin is usually much more active than lincomycin in the treatment of bacterial infections, in particular those caused by anaerobic species; it can also be used for the treatment of important protozoal diseases, e.g. malaria, most effectively in combination with other antibiotic or non-antibiotic antimicrobials (primaquine, fosfidomycin, benzoyl peroxide). Chemical structures of lincosamide antibiotics and the biosynthesis of lincomycin and its genetic control have been summarized and described. Resistance to lincomycin and clindamycin may be caused by methylation of 23S ribosomal RNA, modification of the antibiotics by specific enzymes or active efflux from the bacterial cell.

• Klíčová slova
• Applications, Biosynthesis and mechanism of action, Chemical structure, Lincosamides, Resistance,
• MeSH
• antibakteriální látky chemie   farmakologie   terapeutické užití   MeSH
• bakteriální infekce diagnóza   farmakoterapie   MeSH
• bakteriální léková rezistence účinky léků   fyziologie   MeSH
• lidé MeSH
• linkosamidy chemie   farmakologie   terapeutické užití   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• antibakteriální látky MeSH
• linkosamidy MeSH

MOTIVATION: The existing connections between large databases of chemicals, proteins, metabolites and assays offer valuable resources for research in fields ranging from drug design to metabolomics. Transparent search across multiple databases provides a way to efficiently utilize these resources. To simplify such searches, many databases have adopted semantic technologies that allow interoperable querying of the datasets using SPARQL query language. However, the interoperable interfaces of the chemical databases still lack the functionality of structure-driven chemical search, which is a fundamental method of data discovery in the chemical search space. RESULTS: We present a SPARQL service that augments existing semantic services by making interoperable substructure and similarity searches in small-molecule databases possible. The service thus offers new possibilities for querying interoperable databases, and simplifies writing of heterogeneous queries that include chemical-structure search terms. AVAILABILITY: The service is freely available and accessible using a standard SPARQL endpoint interface. The service documentation and user-oriented demonstration interfaces that allow quick explorative querying of datasets are available at https://idsm.elixir-czech.cz .

• Klíčová slova
• Interoperability, Linked data, Small molecule databases, Substructure search,
• Publikační typ
• časopisecké články MeSH

A prototypical study of NMR chemical shifts in biologically relevant heteroaromatic compounds containing a heavy halogen atom is presented for two isomers of halogen-substituted purines. Complete sets of (1)H-, (13)C- and (15)N-NMR chemical shifts are determined experimentally in solution. Experimental results are complemented by quantum-chemical calculations that provide understanding of the trends in the chemical shifts for the studied compounds and which show how different physical effects influence the NMR parameters. Chemical shifts for isolated molecules are calculated using density-functional theory methods, the role of solvent effects is studied using polarised continuum models, and relativistic corrections are calculated using the leading-order Breit-Pauli perturbation theory. Calculated values are compared with the experimental data and the effects of structure, solvent and relativity are discussed. Overall, we observe a good agreement of theory and experiment. We find out that relativistic effects cannot be neglected even in the chlorine species when aiming at high precision and a good agreement with the experimental data. Relativity plays a crucial role in the bromine and iodine species. Solvent effects are of smaller importance for (13)C shifts but are shown to be substantial for particular (15)N shifts. The test of method performance shows that the BLYP and B3LYP functionals provide the most reliable computational results after inclusion of the solvent and relativistic effects while BHandHLYP may--depending on atom in question--slightly improve but mostly deteriorate the data. Ab initio Hartree-Fock suffers from triplet instability in the Breit-Pauli relativistic part while MP2 provides no clear improvement over DFT in the nonrelativistic region. This work represents the first full application of the Breit-Pauli perturbation theory to an organic chemistry problem.

• MeSH
• halogeny chemie   MeSH
• isomerie MeSH
• krystalografie rentgenová MeSH
• kvantová teorie MeSH
• magnetická rezonanční spektroskopie * MeSH
• molekulární konformace MeSH
• puriny chemie   MeSH
• rozpouštědla chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• halogeny MeSH
• puriny MeSH
• rozpouštědla MeSH

• MeSH
• aminy farmakologie   MeSH
• aziridiny farmakologie   MeSH
• aziriny farmakologie   MeSH
• chemické jevy MeSH
• chemie MeSH
• chemosterilanty farmakologie   MeSH
• chromozomální aberace MeSH
• dominantní geny účinky léků   MeSH
• frekvence genu účinky léků   MeSH
• letální geny účinky léků   MeSH
• meióza účinky léků   MeSH
• mutace účinky léků   MeSH
• mutageny farmakologie   MeSH
• myši MeSH
• spermatogeneze účinky léků   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aminy MeSH
• aziridiny MeSH
• aziriny MeSH
• chemosterilanty MeSH
• mutageny MeSH

This paper describes the Structural and Physico-Chemical Interpretation (SPCI) approach, which is an extension of a recently reported method for interpretation of quantitative structure-activity relationship (QSAR) models. This approach can efficiently be used to reveal structural motifs and the major physicochemical factors affecting the investigated properties. Its efficacy was demonstrated both on the classical Free-Wilson data set and on several data sets with different end points (permeability of the blood-brain barrier, fibrinogen receptor antagonists, acute oral toxicity). Structure-activity patterns extracted from QSAR models with SPCI were in good correspondence with experimentally observed relationships and molecular docking, regardless of the machine learning method used. Comparison of SPCI with the matched molecular pair (MMP) method clearly shows an advantage of our approach over MMP, especially for small or structurally diverse data sets. The developed approach has been implemented in the SPCI software tool with a graphical user interface, which is publicly available at http://qsar4u.com/pages/sirms_qsar.php .

• MeSH
• aplikace orální MeSH
• chemické jevy * MeSH
• data mining MeSH
• hematoencefalická bariéra metabolismus   MeSH
• krysa rodu Rattus MeSH
• kvantitativní vztahy mezi strukturou a aktivitou * MeSH
• oligopeptidy chemie   MeSH
• peptidomimetika chemie   metabolismus   farmakologie   toxicita   MeSH
• permeabilita MeSH
• racionální návrh léčiv MeSH
• receptory fibrinogenu antagonisté a inhibitory   MeSH
• software MeSH
• testy toxicity MeSH
• uživatelské rozhraní počítače MeSH
• výpočetní biologie metody   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• arginyl-glycyl-aspartic acid MeSH Prohlížeč
• oligopeptidy MeSH
• peptidomimetika MeSH
• receptory fibrinogenu MeSH

The efficacy of seven more recently developed anthelmintics of the benzimidazolecarbamate group, i. e., parbendazole, mebendazole, fenbendazole, oxibendazole, cambendazole, oxfendazole and albendazole, has been tested in a series of experiments on white mice artifically infected with Trichinella spiralis. Our results disclosed a relationship between their anthelmintic effect and their chemical structure. This finding might be of importance in a targeted synthesis of new, effective, derivates of benzimidazole, e. g., in the therapy of trichinellosis and in the choice of the most effective drug.

• MeSH
• benzimidazoly farmakologie   terapeutické užití   MeSH
• fenbendazol farmakologie   MeSH
• kambendazol farmakologie   MeSH
• mebendazol farmakologie   MeSH
• myši MeSH
• Trichinella účinky léků   MeSH
• trichinelóza farmakoterapie   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• benzimidazoly MeSH
• fenbendazol MeSH
• kambendazol MeSH
• mebendazol MeSH
• parbendazole MeSH Prohlížeč

Collagen nanofibrous materials have become integral to tissue engineering due to their exceptional properties and biocompatibility. Dehydrothermal crosslinking (DHT) enhances stability and maintains structural integrity without the formation of toxic residues. The study involved the crosslinking of electrospun collagen, applying DHT with access to air and under vacuum conditions. Various DHT exposure times of up to 72 h were applied to examine the time dependance of the DHT process. The DHT crosslinked collagen was subsequently chemically crosslinked using carbodiimides. The material crosslinked in this way evinced elevated Young's modulus values and ultimate tensile strength values, a lower swelling rate and lower shrinkage ratio during crosslinking, and a higher degree of resistance to degradation than the material crosslinked solely with DHT or carbodiimides. It was shown that the crosslinking mechanism using DHT occupies different binding sites than those using chemical crosslinking. Access to air for 12 h or less did not exert a significant impact on the material properties compared to DHT under vacuum conditions. However, concerning longer exposure times, it was determined that access to air results in the deterioration of the properties of the material and that reactions take place that occupy the free bonding sites, which subsequently reduces the effectiveness of chemical crosslinking using carbodiimides.

• Klíčová slova
• Collagen, EDC/NHS, chemical crosslinking, crosslinking, degradation, dehydrothermal crosslinking, swelling, uniaxial tensile tests,
• Publikační typ
• časopisecké články MeSH

Chemical cross-linking coupled with mass spectrometry is a popular technique for deriving structural information on proteins and protein complexes. Also, cross-linking has become a powerful tool for stabilizing macromolecular complexes for single-particle cryo-electron microscopy. However, an effect of cross-linking on protein structure and function should not be forgotten, and surprisingly, it has not been investigated in detail so far. Here, we used kinetic studies, mass spectrometry, and NMR spectroscopy to systematically investigate an impact of cross-linking on structure and function of human carbonic anhydrase and alcohol dehydrogenase 1 from Saccharomyces cerevisiae. We found that cross-linking induces rather local structural disturbances and the overall fold is preserved even at a higher cross-linker concentration. The results establish general experimental conditions for chemical cross-linking with minimal effect on protein structure and function.

• MeSH
• alkoholdehydrogenasa chemie   MeSH
• hmotnostní spektrometrie MeSH
• karboanhydrasy chemie   MeSH
• konformace proteinů MeSH
• lidé MeSH
• molekulární modely MeSH
• multimerizace proteinu MeSH
• nukleární magnetická rezonance biomolekulární MeSH
• reagencia zkříženě vázaná chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• alkoholdehydrogenasa MeSH
• karboanhydrasy MeSH
• reagencia zkříženě vázaná MeSH