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Spektrometria mas w analizie białek i peptydów : znaczniki jonizacyjne

Bąchor R., Biernat M., Cebrat M., Kijewska M., Kluczyk A., Kuczer M., Paluch A., Waliczek M., Wierzbicka M., Stefanowicz P., Szewczuk Z.

Wiadomości Chemiczne

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2018

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[Z] 72, 7-8

609--633

EN

High sensitivity, accuracy, and ability to provide structural information makes mass spectrometry (MS) the method of choice for both qualitative and quantitative analysis in proteome research. Peptide sequencing by tandem mass spectrometry (MS/MS) was successfully applied to discover new peptide sequences and modifications. Insufficient ionization of some peptides is one of the main limitations of MS- based peptide identification. The development of sensitive detection techniques for the efficient analysis of such samples is very important. Differences in ionizability cause difficulties in quantification studies, which could be overcome by derivatization of peptides to improve both the detectability and the selectivity of an analysis. Incorporation of ionization markers and isotopic labels (particularly the isobaric tags) is often used for this reason. Isobaric labeling reagents (including commercially available iTRAQ, TMT, DiLeu and DiART) have found a wide application in quantitative proteomics. Mass spectrometry is a very good tool for the determination of posttranslational modifications (PTMs), but the modified proteins are usually present in low concentrations. The development of ionization tags specific to a particular PTM and suitable for sensitive analysis of the modified proteins is required. For the analysis of phosphorylated peptides, a combination of β-elimination and the reaction of resulting α,β-dehydroamino acid residues with the nucleophilic thiol group could be used to detect a labile PTM. Such reaction may be used to introduce derivatizing reagents at the original site of phosphorylation, to enhance ionization in MS analysis. Glycation and glycosylation of proteins are other very important PTMs associated with many natural processes as well as diseases. We have designed and synthesized bifunctional quaternary ammonium salt derivatives of phenylboronic acids for selective detection of carbohydrates and peptide-derived Amadori products by ESI-MS. The attachment of a fixed charge (e.g. in a form of a quaternary ammonium salt) to the amino groups in peptides leads to the enhancement of a precursor ion signal in mass spectra. We have developed several new QAS-containing ionization reagents including bicyclic tags with DABCO, ABCO or azoniaspiro groups. It is worth noting that 2,4,6-substituted pyrylium salts react with amino groups in peptides introducing a stable positive charge and improve peptide detection by MS. The newly developed ionization tags were successfully applied for the analysis of OBOC combinatorial libraries as well as for studying possible biomarkers of preeclampsia, a pregnancy disorder.

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(E)-Cinnamic Acid Analogues as Inhibitors of Phenylalanine Ammonia-Lyase and of Anthocyanin Biosynthesis

Kluczyk A.

Polish Journal of Chemistry

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2005

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Vol. 79 / nr 3

583-592

EN

Several carboxylic, phosphonic, phosphinic, boronic and nitro analogues of (E)-cinnamic acid were synthesized. These and other compounds related to (E)-cinnamic acid were evaluated as potential inhibitors of both phenylalanine ammonia-lyase and of anthocyanin biosynthesis in buckwheat. The most potent inhibition was found for 3-phenylprop-2-ynoic acid (21), however its Ki is comparable to KM. The molecular modelling of the interaction of (E)-cinnamic acid (1) and 21 with PAL model suggests some similarities in the binding mode of both compounds.

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Krótki kurs historii POP. Część druga : PCB

Mastalerz P., Kluczyk A.

Wiadomości Chemiczne

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2004

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[Z] 58, 1-2

81--130

EN

Polychlorinated biphenyls (PCBs) belong to the family of POPs (Persistent Organic Pollutants) which WHO (World Health Organization), EPA (Environment Protection Agency) and other prestigious institutions pronounced to be a very serious health hazard to humans and animals. It appears, however, that this pronouncement is without solid support in published scientific papers. PCBs were commercially produced since 1929 for use in electrical capacitors and transformers. It is estimated that a total of 1.5 million tons were made until the production was terminated worldwide in late 1970s. About one half of the produced amount is contained in electrical equipments which are still in use while the other half entered the environment. The presence of detectable concentrations of PCBs and their persistence in air, water and in living organisms raised concerns that human and animal health may be adversely affected. Health considerations stimulated a very intense research activity which continues unabated from 1966 with the objective of finding evidence of harmful properties of PCBs. Such evidence has not been found yet apart from some minor effects which are without serious consequences. PCBs appear to be quite harmless chemicals even when handled without proper care. This is evident from the fact that there was no single human death although several cases of poisoning by PCBs were reported. The most publicized are the accidents in Japan and Taiwan which affected about 3000 victims. However, the most serious effects were reversible dermal lesions. The most recent case of accidental poisoning occured in Belgium in 1999. The brouhaha in media was enormous although no human health effects were evident. The case of PCBs is just another example of chemophobia instigated by irresponsible enviromentalists. The three decades of PCB research resulted in enormous improvements in the analysis of trace contaminants. It is now possible to detect and quantitate each of the over one hundred PCB congeners present at concentrations in the ppb range. There are 209 PCB congeners with different numbers and positions of chlorine atoms. This article is based on a thorough search of the literature from late 1960th to the present. Unfortunately it was impossible to read all papers on PCBs in the environment because over three hundred articles are published every year. We took care, however, to learn and present the views of scientists who firmly believe that PCBs are very harmful as well as of those who do not think so. We were able to discover some very drastic examples of papers with unfounded conclusions.