0000000000080441
AUTHOR
Raitis Bobrovs
showing 26 related works from this author
Targeting Bacterial Sortase A with Covalent Inhibitors: 27 New Starting Points for Structure-Based Hit-to-Lead Optimization.
2019
Because of its essential role as a bacterial virulence factor, enzyme sortase A (SrtA) has become an attractive target for the development of new antivirulence drugs against Gram-positive infections. Here we describe 27 compounds identified as covalent inhibitors of
Potent SARS-CoV-2 mRNA Cap Methyltransferase Inhibitors by Bioisosteric Replacement of Methionine in SAM Cosubstrate
2021
Viral mRNA cap methyltransferases (MTases) are emerging targets for the development of broad-spectrum antiviral agents. In this work, we designed potential SARS-CoV-2 MTase Nsp14 and Nsp16 inhibitors by using bioisosteric substitution of the sulfonium and amino acid substructures of the cosubstrate S-adenosylmethionine (SAM), which serves as the methyl donor in the enzymatic reaction. The synthetically accessible target structures were prioritized using molecular docking. Testing of the inhibitory activity of the synthesized compounds showed nanomolar to submicromolar IC50 values for five compounds. To evaluate selectivity, enzymatic inhibition of the human glycine N-methyltransferase invol…
Optimization of sample preparation conditions for detecting trace amounts of β-tegafur in α- and β-tegafur mixture.
2012
We report a semiquantitative method for determining trace amounts (<1%) of thermodynamically stable forms in polymorphic mixtures, focusing on sample preparation ef- fects on solid phase transitions. Tegafur (5-fluoro-1-(oxolan-2-yl)-1,2,3,4-tetrahydropyrimidine- 2,4-dione) was used as a model material in this study. The amounts of the thermodynamically stable $ tegafur were increased to levels detectable by powder X-ray diffractometry by grind- ing the samples in a ball mill in the presence of water. The limit of detection for this method was as low as 0.0005% of $ tegafur in " and $ tegafur mixtures. The amount of $ tegafur after sample preparation was found to be proportional to the init…
Organic solvent desorption from two tegafur polymorphs.
2013
Desorption behavior of 8 different solvents from α and β tegafur (5-fluoro-1-(tetrahydro-2-furyl)uracil) has been studied in this work. Solvent desorption from samples stored at 95% and 50% relative solvent vapor pressure was studied in isothermal conditions at 30 °C. The results of this study demonstrated that: solvent desorption rate did not differ significantly for both phases; solvent desorption in all cases occurred faster from samples with the largest particle size; and solvent desorption in most cases occurred in two steps. Structure differences and their surface properties were not of great importance on the solvent desorption rates because the main factor affecting desorption rate …
Using HOESY NMR Spectroscopy to Characterize Prenucleation Aggregates
2021
Structural and Functional Analysis of BBA03, Borrelia burgdorferi Competitive Advantage Promoting Outer Surface Lipoprotein
2020
BBA03 is a Borrelia burgdorferi outer surface lipoprotein encoded on one of the most conserved plasmids in Borrelia genome, linear plasmid 54 (lp54). Although many of its genes have been identified as contributing or essential for spirochete fitness in vivo, the majority of the proteins encoded on this plasmid have no known function and lack homologs in other organisms. In this paper, we report the solution NMR structure of the B. burgdorferi outer surface lipoprotein BBA03, which is known to provide a competitive advantage to the bacteria during the transmission from tick vector to mammalian host. BBA03 shows structural homology to other outer surface lipoproteins reflecting their genetic …
The reluctant polymorph: investigation into the effect of self-association on the solvent mediated phase transformation and nucleation of theophylline
2015
Little is known concerning the pathway of the crystallization of the thermodynamically stable polymorph of theophylline, form IV. Here we study the reasons why the thermodynamically stable theophylline form IV can be obtained only by slow, solvent mediated phase transformation (SMPT) in specific solvents, and whether the presence of prenucleation aggregates affect the polymorphic outcome. Solution concentration, polymorphic composition and morphology were monitored over time during the transformation from form II to form IV in several solvents. NMR and FTIR spectroscopy were used to detect prenucleation molecular aggregates present in the solutions. It was determined that theophylline self-…
Organic solvent vapor effects on phase transition of α and β tegafur upon grinding with solvent additives.
2012
Abstract Solvent effects on α tegafur (5-fluoro-1-(tetrahydro-2-furyl)uracil) phase transition to β tegafur during grinding with solvent additive, as well as phase transition in samples exposed to 95% relative solvent vapor pressure has been studied in this research. Samples containing 0.5% and 0.1% of β tegafur in α and β tegafur mixture, as well as samples of pure α tegafur were ground with different solvent additives, and conversion degrees depending on the solvent were determined using PXRD method. Samples with α and β tegafur weight fraction of 1:1 were exposed to 95% relative solvent vapor pressure, and phase transition rates were determined. Solubility of α tegafur, solvent sorption …
Three anhydrous forms and a dihydrate form of quifenadine hydrochloride: a structural study of the thermodynamic stability and dehydration mechanism
2015
Crystal structures of dihydrate (DH) and three anhydrous forms (A, B and C) of quifenadine (1-azabicyclo[2.2.2]oct-8-yl-diphenyl-methanol) hydrochloride are presented, and crystal structure information is used to explain and rationalize the relative stability of polymorphs and observed phase transformations. The dehydration mechanism of the hydrate is provided by interpreting the results obtained in studies of crystal structures, dehydration kinetics and thermal analysis. Structural analysis is used to explain the observed relative stability of the anhydrous phases and the hydrate. The crystal structures have been determined either from single crystal (form DH) or from powder diffraction da…
Organic solvents vapor pressure and relative humidity effects on the phase transition rate of α and β forms of tegafur.
2011
The objective of this work was to investigate the relative humidity (RH) and solvent vapor pressure effects on the phase transition dynamics between tegafur polymorphic forms that do not form hydrates and solvates. The commercially available α and β modifications of 5-fluoro-1-(tetrahydro-2-furyl)-uracil, known as the antitumor agent tegafur, were used as model materials for this study. While investigating the phase transitions of α and β tegafur under various partial pressures of methanol, n-propanol, n-butanol, and water vapor, it was determined that the phase transition rate increased in the presence of solvent vapors, even though no solvates were formed. By increasing the relative air h…
Formation and Transformations of Organic Salt Hydrates: Four Encenicline Hydrochloride Monohydrates and Respective Isostructural Desolvates
2018
Encenicline hydrochloride (Enc-HCl) crystallizes in four different monohydrate phases, but at the same time crystallization in a nonsolvated phase is not observed, indicating that water plays a crucial role in guiding the crystallization process and ensuring structure stability. All monohydrate phases show exceptionally high stability, and the main structural motif stays intact even after dehydration, leading to isostructural (for I and II) or isomorphic (for III) desolvates. Three monohydrate phases with determined crystal structure information consists of Enc-HCl-water hexamers that are stacked into similar slabs, that are further packed identically in monohydrates I, II, and III. The fea…
Determination of trace amounts of β tegafur in commercial α tegafur by powder X-ray diffractometric analysis.
2011
Abstract Objectives The main objective of this work was to develop a suitable analytical technique for determining trace amounts of the thermodynamically stable solid form in bulk samples of metastable form, to a sensitivity of 0.005%–1.0%. Tegafur (5-fluoro-1-(tetrahydro-2-furyl)-uracil) α and β crystalline forms were used as a model for this problem. Methods The trace content of the thermodynamically stable β polymorphic form in tegafur samples was increased by promoting phase transition from the bulk of thermodynamically metastable α form to β form, and achieving sufficient β form content for a quantitative powder X-ray diffractometry (PXRD) analysis. The phase transition was stimulated …
Solvent-mediated phase transformation between two tegafur polymorphs in several solvents
2014
This paper describes a study of the solvent-mediated polymorphic transformation (SMPT) of the metastable α tegafur to the thermodynamically stable β tegafur in several solvents. Phase transformation in acetone, ethanol, i-propanol, toluene, and water at 22 °C was described using the solid-state kinetic model P2; the rate constants for this process were in the range from 0.028 min−1 to 0.0056 min−1. In all of the employed solvents, an induction time was observed. Kinetic, solubility and scanning electron microscopy data indicated that nucleation kinetics corresponded to a second-order power function and according to the kinetic model, the nuclei growth rate was constant in the examined SMPT.…
Farmaceitiski aktīvo cietvielu florafūra un teofilīna šķīdinātāja veicinātas cietfāžu pārejas
2015
Elektroniskā versija nesatur pielikumus
Ftorafūra polimorfos formu kristalizācija un fāžu pārejas
2009
Darbā apskatīta daļiņu izmēra un gaisa relatīvā mitruma ietekme uz ftorafūra α- un β- fāžu pārejas kinētiku dažādās temperatūrās. Ftorafūra α- un β- kristālisko modifikāciju maisījumos abu formu saturu noteica, veicot pilna profila analīzi. Noteikta ftorafūra α- un β- līdzsvara temperatūra, izmantojot karsēšanas metodi un šķīšanas metodi, kā arī α- un γ- formu līdzsvara temperatūras, izmantojot karsēšanas metodi. Izmantojot noteiktās līdzsvara un kušanas temperatūras, aprēķināta ftorafūra β- un γ- formu līdzsvara temperatūra. Noteikti optimāli apstākļi ftorafūra ε- formas kristalizācijai no spirtu šķīdumiem.
CCDC 1584618: Experimental Crystal Structure Determination
2018
Related Article: Raitis Bobrovs, Artis Kons, Agris Be¯rzinš, Toms Rekis, Andris Actinš|2018|Cryst.Growth Des.|18|2100|doi:10.1021/acs.cgd.7b01561
CCDC 1051734: Experimental Crystal Structure Determination
2015
Related Article: Artis Kons, Ligita Rutkovska, Agris Bērziņš, Raitis Bobrovs, Andris Actiņš|2015|CrystEngComm|17|3627|doi:10.1039/C5CE00426H
CCDC 1584619: Experimental Crystal Structure Determination
2018
Related Article: Raitis Bobrovs, Artis Kons, Agris Be¯rzinš, Toms Rekis, Andris Actinš|2018|Cryst.Growth Des.|18|2100|doi:10.1021/acs.cgd.7b01561
CCDC 1584616: Experimental Crystal Structure Determination
2018
Related Article: Raitis Bobrovs, Artis Kons, Agris Be¯rzinš, Toms Rekis, Andris Actinš|2018|Cryst.Growth Des.|18|2100|doi:10.1021/acs.cgd.7b01561
CCDC 1584621: Experimental Crystal Structure Determination
2018
Related Article: Raitis Bobrovs, Artis Kons, Agris Be¯rzinš, Toms Rekis, Andris Actinš|2018|Cryst.Growth Des.|18|2100|doi:10.1021/acs.cgd.7b01561
CCDC 1584620: Experimental Crystal Structure Determination
2018
Related Article: Raitis Bobrovs, Artis Kons, Agris Be¯rzinš, Toms Rekis, Andris Actinš|2018|Cryst.Growth Des.|18|2100|doi:10.1021/acs.cgd.7b01561
CCDC 1584617: Experimental Crystal Structure Determination
2018
Related Article: Raitis Bobrovs, Artis Kons, Agris Be¯rzinš, Toms Rekis, Andris Actinš|2018|Cryst.Growth Des.|18|2100|doi:10.1021/acs.cgd.7b01561
CCDC 1051733: Experimental Crystal Structure Determination
2015
Related Article: Artis Kons, Ligita Rutkovska, Agris Bērziņš, Raitis Bobrovs, Andris Actiņš|2015|CrystEngComm|17|3627|doi:10.1039/C5CE00426H
CCDC 1051731: Experimental Crystal Structure Determination
2015
Related Article: Artis Kons, Ligita Rutkovska, Agris Bērziņš, Raitis Bobrovs, Andris Actiņš|2015|CrystEngComm|17|3627|doi:10.1039/C5CE00426H
CCDC 1051732: Experimental Crystal Structure Determination
2015
Related Article: Artis Kons, Ligita Rutkovska, Agris Bērziņš, Raitis Bobrovs, Andris Actiņš|2015|CrystEngComm|17|3627|doi:10.1039/C5CE00426H
CCDC 1584615: Experimental Crystal Structure Determination
2018
Related Article: Raitis Bobrovs, Artis Kons, Agris Be¯rzinš, Toms Rekis, Andris Actinš|2018|Cryst.Growth Des.|18|2100|doi:10.1021/acs.cgd.7b01561