Chiral LC Dotaz Zobrazit nápovědu
Mnoho léčiv obsahuje ve své molekule chirální centrum/centra a vyskytují se proto ve dvou či více enantiomerních formách. Lidské tělo je ve svém principu také chirální strukturou s řadou chirálních cílů pro léčiva. Proto mohou mít rozdílné enantiomery téhož léčiva rozdílný farmakologický účinek na enzymy, receptory, iontové kanály apod. V posledních dvou desetiletích sílí snaha o vývoj léků založených pouze na jednom, účinném enantiomeru. Nejnovější zkušenosti ukazují, že farmakologická aktivita enantiomerů chirálních léčiv se může projevit mnoha způsoby. Například má-li jeden enantiomer požadovaný terapeutický účinek, druhý enantiomer se může chovat úplně jinak. Z preklinických studií vyplývá, že u mnoha účinných, již běžně používaných racemických léčiv, existuje možnost zlepšení poměru riziko/přínos zavedením jejich vhodné chirální formy. Tento trend můžeme vysledovat i v psychofarmakologii.
A large proportion of therapeutics posses chiral centre/centers and therefore exist in two or more enantiomeric forms. Since the human body is essentially a chiral structure incorporating many chiral drug targets, such as enzymes, receptors, and ion channels, different enatiomers of the same drug can have diverse biological effect. In the past two decades there has been an increasing trend towards the development only of single, effective enantiomer drugs. Present-day experience suggests that the pharmacological activity of the enantiomers of chiral drugs can follow several distinct patterns. For instance, if one enantiomer contains the therapeutic activity of interest, the second enantiomer may differ by substantial manner. Preclinical studies suggest that a number of effective racemic drugs already in widespread use as racemates have the potential for an improved risk/benefit ratio in enantiomeric form. This trend may be also very effective in psychiatry.
- MeSH
- antidepresiva farmakologie chemie MeSH
- lidé MeSH
- psychiatrie MeSH
- psychotropní léky farmakologie chemie terapeutické užití MeSH
- stereoizomerie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
LC with atmospheric pressure chemical ionization (ACPI) MS with RP and chiral phase was used for separation of triacylglycerols (TAGs) from yeasts of the genera Candida, Kluyveromyces, Rhodotorula, Saccharomyces, Torulospora, Trichosporon, and Yarrowia. Chiral LC-APCI-MS is based on using two columns in series packed with a 3,5-dimethylphenyl carbamate modified β-cyclodextrin chiral phase. All regioisomers and enantiomers of TAGs containing one to five double bonds were separated. Molecular species of TAGs, i.e. regioisomers and enantiomers, were identified and quantified by MS/MS. Among the 94 identified TAGs, the most abundant were triolein, oleopalmitoleoolein, and dipalmitoleoolein. In strains producing palmitoleic acid in amounts >25% of total fatty acids (FAs), this acid, or unsaturated FA is bound in sn-1. In strains containing palmitoleic acid at 10-25% total FAs this acid is mainly bound in sn-3, saturated FA being bound in sn-1. Strains containing <10% palmitoleic acid form preferentially symmetrical TAGs.
Glucuronidation of the non-steroidal anti-inflammatory chiral drug flobufen and its major metabolite M17203 has been implicated as an important mechanism of flobufen elimination. To characterize flobufen metabolism by O-glucuronidation, new liquid chromatographic method (LC) coupled with ESI-MS was developed to detect the conjugates of flobufen and its metabolites formed in vitro in rat liver microsomes. Discovery DSC-18 LT cartridge columns were utilized for solid phase extraction (SPE) and Discovery C18 column (150 mm x 2.1 mm, 5 microm particle size) was used for LC separation. Chiral inversion of flobufen and its metabolites enantiomers was checked by special 1-allyl-(5R,8S,10R)-terguride column (150 mm x 4.6 mm). O-Glucuronidation of the S-enantiomer displayed a typical Michaelis-Menten kinetics, whereas the R-enantiomer exhibited a substrate inhibition type of kinetics. The study of glucuronidation of M17203 led to kinetics with sigmoidal characteristics.
- MeSH
- butyráty analýza MeSH
- financování organizované MeSH
- hmotnostní spektrometrie s elektrosprejovou ionizací metody MeSH
- jaterní mikrozomy metabolismus MeSH
- krysa rodu rattus MeSH
- potkani Wistar MeSH
- vysokoúčinná kapalinová chromatografie metody MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
Liquid chromatography-atmospheric pressure chemical ionization mass spectrometry (LC-MS/APCI) with a chiral phase was used for separation of triacylglycerols (TAG) obtained either by organic synthesis or isolated from different algal species. We present chromatographic characteristics and tandem mass spectra of enantiomers and positional isomers (regioisomers) of C16, C18 and C20 polyunsaturated fatty acids. The retention time was found to depend on the structure of the given TAG, increasing with increasing number of double bonds and decreasing with increasing number of the carbons in TAG, with the exception of dieicosapentaenoyl-palmitoyl-glycerols.
- MeSH
- Chlorophyta chemie MeSH
- hmotnostní spektrometrie metody MeSH
- molekulární struktura MeSH
- nenasycené mastné kyseliny analýza chemie izolace a purifikace MeSH
- stereoizomerie MeSH
- tandemová hmotnostní spektrometrie metody MeSH
- triglyceridy analýza chemie MeSH
- vysokoúčinná kapalinová chromatografie metody normy MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Liquid crystals (LCs) are among the most prominent materials of the current information age, mainly due to their well-known application in liquid crystal displays (LCDs). Their unique electro-optical properties stem from their ability to form organised structures (mesophases) on the transition from solid state to isotropic liquid. Molecules of LCs in a mesophase still maintain the anisotropy of solid crystals, while simultaneously exhibiting the fluidity of liquids, which gives the system the ability to react immediately to external stimuli such as electric or magnetic fields, light, mechanical stress, pressure and, of course, temperature. For the proper function of LC-based devices, not only chemical, but also optical purity of materials is strongly desirable, since any impurity could be detrimental to the self-assembly of the molecules. Therefore, in this study we aimed to verify synthetic methods published in the literature, which are used nowadays to prepare chiral building blocks based on lactic acid, for their enantioselectivity. Moreover, we have focused on the development of an analytical chiral separation method for target liquid crystalline materials. Using a chiral polysaccharide-based column operated in liquid chromatography mode, we show that not all published methods of LC synthesis are enantioselective, which could lead to significant differences in the properties of the resulting materials. We show that high-performance liquid chromatography with UV detection and supercritical fluid chromatography with UV and mass spectrometry detection enable full control over the chemical and optical purity of the target LCs and the corresponding chiral building blocks. For the first time, we utilise supercritical fluid chromatography with mass detection for the direct chiral analysis of liquid crystalline materials and impurities formed during the synthesis.
Collagen is the most abundant protein in the animal and human bodies, and it is not exempt from this aging phenomenon. Some age-related changes may appear on collagen sequences, such as increased surface hydrophobicity, the appearance of post-translational modifications, and amino acids racemization. This study has shown that the protein hydrolysis under deuterium conditions is privileged to limit the natural racemization during the hydrolysis. Indeed, under the deuterium condition, the homochirality of recent collagens is preserved whose amino acids are found in their L-form. However, in aging collagen, a natural amino acid racemization was observed. These results confirmed that the % d-amino acids are progressive according to age. The collagen sequence is degraded over time, and a fifth of the sequence information is lost during aging. Post-translational modifications (PTMs) in aging collagens can be a hypothesis to explain the modification of the hydrophobicity of the protein with the decrease of hydrophilic groups and the increase of hydrophobic groups. Finally, the exact positions of d-amino acids and PTMs have been correlated and elucidated.
- MeSH
- aminokyseliny * chemie MeSH
- chromatografie kapalinová MeSH
- deuterium chemie MeSH
- kolagen MeSH
- lidé MeSH
- posttranslační úpravy proteinů MeSH
- proteomika * MeSH
- stárnutí MeSH
- tandemová hmotnostní spektrometrie metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
HPLC methods (LC-MS/APCI and chiral HPLC) were used for the identification of astaxanthin derivatives from the red snow alga Chlamydomonas nivalis collected in Austrian Alps, Slovak High Tatra Mountains and Bulgarian Pirin. We observed a striking difference in the composition of astaxanthin optical isomers in C. nivalis collected in geographically distinct regions. Furthermore, algae from the Pirin Mountains differed in the dominance of astaxanthin diglucoside diesters, suggesting an alternative strategy to enhance cell viability at low temperatures.
- MeSH
- Chlamydomonas chemie MeSH
- chromatografie kapalinová * MeSH
- estery chemie MeSH
- glukosidy chemie MeSH
- hmotnostní spektrometrie * MeSH
- molekulární struktura MeSH
- nízká teplota MeSH
- stereoizomerie MeSH
- viabilita buněk MeSH
- xanthofyly chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Liquid chromatography-atmospheric pressure chemical ionization mass spectrometry (LC-MS/APCI) with reversed- and chiral phases was used for separation of triacylglycerols (TAG) from protozoan and mold. This study describes the separation and identification of odd numbered chains of regioisomers and enantiomers of triacylglycerols from different natural sources, i.e., the protozoan Khawkinea quartana and the mold Mortierella alpina. Using the above-mentioned separation methods and the synthesis of appropriate standards of TAG, we identified regioisomers and enantiomers of both even and odd numbered TAG. The biosynthesis of odd numbered TAG was found to be strictly stereospecific and to depend on the production microorganism, one enantiomer predominating in the protozoan and the other in the mold. It was proved that even numbered TAG are synthesized in a higher optical purity, which can be explained by a higher affinity of acyltransferases to the respective substrate, i.e., to even chain PUFA.
Cardiolipins (1,3-bis(sn-3'-phosphatidyl)-sn-glycerol) (CLs) are widespread in many organisms, from bacteria to higher green plants and mammals. CLs were observed in Gram-positive bacterium of the genus Kocuria, brewer's yeast Saccharomyces, the green alga Chlamydomonas, spinach and beef heart. A mixture of molecular species of CLs was obtained from total lipids by hydrophilic interaction liquid chromatography (HILIC), and these were further separated and identified by reversed phase LC/MS with negative tandem electrospray ionization. The majority of CLs molecular species from each organism were cleaved using phospholipase C from Bacillus cereus. This phospholipase cleaves CLs into 1,2-diglycerols and phosphatidylglycerol 3-phosphates, which were then separated. After CLs cleavage, diacylglycerols such as sn-1,2-diacyl-3-acetyl-glycerols (i.e., triacylglycerols) were separated and identified by chiral chromatography/MS-positive tandem ESI. Significant differences in the composition of the molecular species between the 3-(3-sn-phosphatidyl) and 1-(3-sn-phosphatidyl) moieties of CLs were found in all organisms tested. Molecular species of CLs that contained four different fatty acids were identified in all five samples, and CLs containing very long chain fatty acids were identified in yeast. In addition, CLs containing both enantiomers (at the sn-2 carbon) were present in the bacterium tested. These findings were further supported by data already published in GenBank where, in the same family - Micrococcaceae - both enzymes responsible for chirality in the sn-2 position, glycerol-3-phosphate and glycerol-1-phosphate dehydrogenases, were present.
- MeSH
- chemická frakcionace MeSH
- Chlamydomonas reinhardtii chemie MeSH
- chromatografie kapalinová metody MeSH
- hmotnostní spektrometrie s elektrosprejovou ionizací metody MeSH
- hydrofobní a hydrofilní interakce MeSH
- hydrolýza MeSH
- kardiolipiny chemie MeSH
- mastné kyseliny analýza MeSH
- skot MeSH
- stereoizomerie MeSH
- triglyceridy chemie MeSH
- zvířata MeSH
- Check Tag
- skot MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Chiral high-performance liquid chromatography was employed for determination of the enantiomeric purity of levodopa and methyldopa. The determination of D-DOPA in levodopa was accomplished using a chiral ligand-exchange chromatograpy with an ordinary C18 column and a chiral mobile phase containing N,N-dimethyl-L-phenylalanine and Cu(II) acetate or by means of LC on a teicoplanin column in conjunction with ethanol-water (65:35, v/v). Both methods gave good performance, however, the latter was faster and more convenient and suitable for routine analyses. For the determination of D-methyldopa a LC method based on the use of a teicoplanin column in polar organic mode with methanol-acetic acid-triethylamine (1,000:0.05:0.05, v/v/v) mobile phase was developed. The precision, accuracy, linearity and selectivity were satisfactory. In comparison with pharmacopoeial polarimetric methods (according to the European Pharmacopoeia and the Pharmacopoea Bohemoslovaca), the LC methods proved to be much more sensitive giving detection limits 0.04% of D-DOPA and 0.3% of D-methyldopa.
- MeSH
- farmakopea jako téma * normy MeSH
- hodnotící studie jako téma MeSH
- levodopa * analýza izolace a purifikace MeSH
- ligandy MeSH
- methyldopa * analýza izolace a purifikace MeSH
- optická otáčivost MeSH
- reprodukovatelnost výsledků MeSH
- rozpouštědla MeSH
- senzitivita a specificita MeSH
- stereoizomerie MeSH
- teikoplanin chemie MeSH
- vysokoúčinná kapalinová chromatografie metody MeSH
- Publikační typ
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Geografické názvy
- Česká republika MeSH
- Evropa MeSH