• MeSH
• chromatografie na tenké vrstvě MeSH
• kyselina oxolinová analogy a deriváty   analýza   chemická syntéza   MeSH

• MeSH
• bipolární porucha diagnóza   klasifikace   MeSH
• depresivní porucha unipolární diagnóza   MeSH
• lidé MeSH
• osobnostní dotazník MeSH
• psychotické poruchy psychologie   MeSH
• Check Tag
• lidé MeSH

Concentrations and isomer compositions of hexabromocyclododecane (HBCD) were measured in six matrices in the Czech Republic (HBCD technical mixture; consumer products; indoor and outdoor air at industrial, urban and background locations; soils; and sediments) to provide insight into changes in concentrations and isomer profiles between environmental sources and environmental sinks. A distinct gradient of air concentrations was observed, from 1600 ng/m3 in the industrial area to < 10 pg/m3 in urban and background air. Isomer profiles also showed a distinct gradient in air, from 95% γ-HBCD in industrial air to 40% γ-HBCD in background air, suggesting the influence of differential atmospheric transport and phototransformation of γ- to α-HBCD. Concentrations and isomer compositions in consumer products were highly variable and indicated differences between products with intentional addition of HBCD as a flame retardant versus those with HBCD as an impurity, e.g., from recycled plastic. Understanding the isomer-specific environmental distributions and processes remains important for risk assessment and toxicology, considering the continued use of HBCD and the isomer-specific differences in uptake, metabolism, and toxicity, and further, demonstrates the utility of isomer profiles to better understand environmental processes of HBCDs.

• MeSH
• bromované uhlovodíky analýza   chemie   MeSH
• isomerie MeSH
• látky znečišťující životní prostředí analýza   chemie   MeSH
• monitorování životního prostředí metody   MeSH
• půda chemie   MeSH
• retardanty hoření analýza   MeSH
• spotřebitelská bezpečnost produktů MeSH
• vzduch analýza   MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

In this work, the synthesis, characterization, and chiral capillary electrophoretic study of heptakis-(2,3-di-O-methyl-6-O-carboxymethyl)-β-CD (HDMCM), a single-isomer carboxymethylated CD, are presented. The pH-dependent and selector concentration-dependent enantiorecognition properties of HDMCM were investigated and discussed herein. The enantioseparation was assessed applying a structurally diverse set of noncharged, basic, and zwitterionic racemates. The increase in the selector concentration and gross negative charge of HDMCM improved the enantioseparation that could be observed in the majority of the cases. HDMCM was also successfully applied as BGE additive in NACE using a methanol-based system in order to prove the separation selectivity features and to highlight the broad applicability of HDMCM. Over 25 racemates showed partial or baseline separation with HDMCM under the conditions investigated, among which optimal enantiomer migration order was found for the four stereoisomers of tadalafil, tapentadol, and dapoxetine, offering the possibility of a chiral CE method development for chiral purity profiling of these drugs.

• MeSH
• beta-cyklodextriny chemie   MeSH
• elektroforéza kapilární přístrojové vybavení   metody   MeSH
• koncentrace vodíkových iontů MeSH
• léčivé přípravky analýza   chemie   izolace a purifikace   MeSH
• methanol chemie   MeSH
• stereoizomerie MeSH
• Publikační typ
• časopisecké články MeSH

Herein we report on the synthesis, characterization and the novel capillary electrophoretic use of octakis-(2,3-di-O-methyl-6-O-carboxymethyl)-γ-cyclodextrin sodium salt (ODMCM). ODMCM is the first single-isomer carboxymethyl-γ-cyclodextrin that is fully methylated on its secondary side and carries ionizable carboxymethyl functions on its primary side. ODMCM was prepared with high isomeric purity through a four-step synthetic procedure. The purity of each intermediate was characterized by appropriate chromatographic methods, while the isomeric purity of the carboxymethylated product was determined by an HPLC method using a CD-Screen-IEC column and by a capillary electrophoretic method using indirect UV detection, as well. The structural identification of the ODMCM was carried out by 1D, 2D NMR spectroscopy and ESI-MS. The acid-base characterization of the chiral selector was carried out by (1)H NMR-pH titration. The chiral separation ability of the synthesized selector was studied by chiral capillary electrophoresis. ODMCM was used as a background electrolyte additive to separate enantiomers of representative pharmacologically significant model molecules such as propranolol, citalopram, ketamine, tapentadol and dapoxetine. The effects of the selector concentration and the pH of the background electrolyte on the enantiorecognition properties were investigated. (1)H NMR spectroscopy was further applied to get deeper insight of the host-guest inclusion complex formation. The pH-dependent enantioselectivity of this new single-isomer chiral selector was demonstrated by chiral capillary electrophoresis and (1)H NMR spectroscopy.

• MeSH
• elektroforéza kapilární * MeSH
• gama-cyklodextriny chemie   MeSH
• hmotnostní spektrometrie s elektrosprejovou ionizací * MeSH
• indikátory a reagencie MeSH
• koncentrace vodíkových iontů MeSH
• magnetická rezonanční spektroskopie MeSH
• spektrofotometrie ultrafialová * MeSH
• stereoizomerie MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• Publikační typ
• časopisecké články MeSH

This contribution reports the synthesis, characterization and capillary electrophoretic application of heptakis-(6-O-sulfobutyl-ether)-β-cyclodextrin sodium salt, (6-(SB)7-β-CD). The compound was obtained through a five-steps synthesis and it represents the first example of single-isomer sulfobutylated cyclodextrin that carries the negatively charged functions exclusively on its primary side and it is unmodified on the lower rim. The purity of each intermediate was determined by appropriate liquid chromatographic methods, while the isomeric purity of the final product was established by an ad-hoc developed HPLC method based on a CD-Screen-IEC column. The structural identification of 6-(SB)7-β-CD was carried out by 1D, 2D NMR spectroscopy and ESI-MS. The chiral separation ability of 6-(SB)7-β-CD was studied by chiral capillary electrophoresis using the single-isomer host as a background electrolyte additive to separate the enantiomers of a representative set of pharmacologically significant model compounds such as verapamil, dapoxetine, ondansetron, propranolol, atenolol, metoprolol, carvedilol, terbutaline, amlodipine and tadalafil. The enantiomer migration order and the effects of the selector concentration on the enantiorecognition properties were investigated. NMR spectroscopy was applied to deepen and further confirm the host-guest interactions and in the case of the model compound dapoxetine a potential representation for the supramolecular assembly was developed based on the dataset collected by the extensive 2D NMR analysis. This single-isomer chiral selector offers a new alternative to the widely applied randomly sulfobutylated- and sulfated-beta-cylodextrins as well as to the single-isomer sulfated and carboxymethylated derivatives in chiral separations.

• MeSH
• beta-cyklodextriny analýza   chemická syntéza   chemie   MeSH
• elektroforéza kapilární metody   MeSH
• elektrolyty MeSH
• hmotnostní spektrometrie s elektrosprejovou ionizací MeSH
• koncentrace vodíkových iontů MeSH
• magnetická rezonanční spektroskopie MeSH
• stereoizomerie MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• Publikační typ
• časopisecké články MeSH

The antimicrobial 40-amino-acid-peptide lucifensin was synthesized by native chemical ligation (NCL) using N-acylbenzimidazolinone (Nbz) as a linker group. NCL is a method in which a peptide bond between two discreet peptide chains is created. This method has been applied to the synthesis of long peptides and proteins when solid-phase synthesis is imcompatible. Two models of ligation were developed: [15+25] Ala-Cys and [19+21] His-Cys. The [19+21] His-Cys method gives lower yield because of the lower stability of 18-peptide-His-Nbz-CONH2 peptide, as suggested by density functional theory calculation. Acetamidomethyl-deprotection and subsequent oxidation of the ligated linear lucifensin gave a mixture of lucifensin isomers, which differed in the location of their disulfide bridges only. The dominant isomer showed unnatural pairing of cysteines [C1-6], [C3-5], and [C2-4], which limits its ability to form α-helical structure. The activity of isomeric lucifensin toward Bacillus subtilis, Staphylococcus aureus, and Micrococcus luteus was lower than that of the natural lucifensin. The desired product native lucifensin was prepared from this isomer using a one-pot reduction with dithiotreitol and subsequent air oxidation in slightly alkaline medium.

• MeSH
• antiinfekční látky * chemická syntéza   chemie   farmakologie   MeSH
• defensiny * chemická syntéza   chemie   farmakologie   MeSH
• grampozitivní bakterie růst a vývoj   MeSH
• kationické antimikrobiální peptidy * chemická syntéza   chemie   farmakologie   MeSH
• sekundární struktura proteinů MeSH
• Publikační typ
• časopisecké články MeSH

2-Ethylhexyl methoxycinnamate (EHMC) is one of the most used ultraviolet filters in personal care products. It undergoes cis/trans isomerization in sunlight, and there is limited toxicological understanding of the effects of the cis-isomer. It is known that two geometric isomers of one compound can have different physico-chemical properties and effects. However, there are no studies focusing on toxicokinetics of EHMC isomerization products to compare their potential difference in dermal exposure to cis-EHMC and trans-EHMC due to the difference in their dermatotoxicokinetics. In this study, dermal absorption of the parental trans-EHMC and its cis isomer was studied. A commercially available sunscreen lotion containing trans-EHMC and spiked with laboratory-prepared cis-EHMC was locally applied on the forearm skin of two volunteers. After 8 h of skin exposure, the stratum corneum (SC) layer was removed by tape stripping. The removed thickness of the SC was determined spectrophotometrically using a total protein assay. The concentration of both isomers in the removed SC was measured by HPLC-DAD. A new diffusion and permeability coefficient of both EHMC isomers in SC were determined by Fick's second law of diffusion in vivo. The difference in dermatotoxicokinetic parameters between the two isomers was not statistically significant. However, separate toxicological studies of isomeric forms and the determination of their dermatotoxicokinetic parameters are crucial for refinement of human risk assessment.

• MeSH
• cinnamáty chemie   farmakokinetika   MeSH
• dospělí MeSH
• epidermis metabolismus   MeSH
• kožní absorpce * MeSH
• lidé MeSH
• přípravky chránící proti slunci chemie   farmakokinetika   MeSH
• stereoizomerie MeSH
• toxikokinetika MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• Publikační typ
• abstrakt z konference MeSH

Recognition and processing by cellular proteins of DNA modified by platinum complexes have been suggested to be relevant to the mechanism of their antitumor activity. Platinum complexes form on DNA various mono- and bifunctional adducts. It has already been described by other authors that intrastrand cross-links formed on DNA by antitumor cis-diamminedichloroplatinum(II) (cisplatin) between neighboring purine residues are recognized by several DNA-binding proteins. In contrast, these proteins do not recognize the intrastrand cross-links formed on DNA by cisplatin or its clinically ineffective trans isomer (transplatin) between nonadjacent base residues. An eventuality heretofore not addressed is that DNA interstrand cross-links (ICLs) of platinum compounds may be recognized by and bound to DNA-binding proteins. DNA probes of 110 base pairs (bp) were constructed containing five equally spaced ICLs of cisplatin or transplatin. These ICLs were formed at specific sites at which these adducts are preferentially formed in natural DNA. Gel electrophoresis mobility shift and competition assays with these probes were used to investigate the specific recognition and binding of the calf thymus HMG1 protein to the DNA ICLs of both platinum isomers. The ICL of antitumor cisplatin was recognized by and bound to the HMG1 protein with a similar affinity as the 1,2-intrastrand d(GpG) cross-link of this drug. The protein binding to the ICL is selective for the DNA modification by cisplatin, but not by chemotherapeutically inactive transplatin.(ABSTRACT TRUNCATED AT 250 WORDS)

• MeSH
• adukty DNA * metabolismus   MeSH
• antitumorózní látky * metabolismus   MeSH
• cisplatina * metabolismus   MeSH
• DNA footprinting MeSH
• DNA vazebné proteiny * metabolismus   MeSH
• endodeoxyribonukleasy metabolismus   MeSH
• kompetitivní vazba MeSH
• konformace nukleové kyseliny MeSH
• molekulární sekvence - údaje MeSH
• poškození DNA MeSH
• proteiny s vysokou pohyblivostí metabolismus   MeSH
• reagencia zkříženě vázaná * metabolismus   MeSH
• sekvence nukleotidů MeSH
• substrátová specifita MeSH
• vazba proteinů MeSH
• Publikační typ
• práce podpořená grantem MeSH
• srovnávací studie MeSH