What's new for 'Trypanosomatids' in PubMed

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Sent on Tuesday, 2011 Oct 18
Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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PubMed Results

Items 1 - 5 of 5

1.	Rapid Commun Mass Spectrom. 2011 Nov 30;25(22):3447-52. doi: 10.1002/rcm.5247. Semi-targeted analysis of metabolites using capillary-flow ion chromatography coupled to high-resolution mass spectrometry. Burgess K, Creek D, Dewsbury P, Cook K, Barrett MP. Source Scottish Metabolomics Facility, University of Glasgow, Glasgow, UK; Institute of Infection, Immunity and Inflammation, Wellcome Trust Centre for Molecular Parasitology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK. karl.burgess@glasgow.ac.uk. Abstract This work describes a novel application of capillary-flow ion chromatography mass spectrometry for metabolomic analysis, and comparison of the technique to octadecyl silica and hydrophilic interaction chromatography (HILIC)-based mass spectrometry. While liquid chromatography/mass spectrometry (LC/MS) is rapidly becoming the standard technique for metabolomic analysis, metabolomic samples are extremely heterogeneous, leading to a requirement for multiple methods of analysis and separation techniques to perform a 'global' metabolomic analysis. While C18 is suitable for hydrophobic metabolites and has been used extensively in pharmaceutical drug metabolism studies, HILIC is, in general, efficient at separating polar metabolites. Phosphorylated species and organic acids are challenging to analyse and effectively quantitate on both systems. There is therefore a requirement for an MS-compatible analytical technique that can separate negatively charged compounds, such as ion-exchange chromatography. Evaluation of capillary flow ion chromatography with electrolytic suppression was performed on a library of metabolite standards and was shown to effectively separate organic acids and sugar di- and tri-phosphates. Limits of detection for these compounds range from 0.01 to 100 pmol on-column. Application of capillary ion chromatography to a comparative analysis of energy metabolism in procyclic forms of the parasitic protozoan Trypanosoma brucei where cells were grown on glucose or proline as a carbon source was demonstrated to be more effective than HILIC for detection of the organic acids that comprise glucose central metabolism and the tricarboxylic acid (TCA) cycle. Copyright © 2011 John Wiley & Sons, Ltd. Copyright © 2011 John Wiley & Sons, Ltd.
	PMID: 22002700 [PubMed - in process]

2.	Curr Opin Infect Dis. 2011 Oct 13. [Epub ahead of print] Boron-based drugs as antiprotozoals. Jacobs RT, Plattner JJ, Keenan M. Source aSCYNEXIS Inc., North Carolina bAnacor Pharmaceuticals Inc., Palo Alto, California, USA cEpichem Pty Ltd, Murdoch University Campus, Murdoch, Western Australia, Australia. Abstract PURPOSE OF REVIEW: Boron-based drugs represent a new class of molecules that have been found to exhibit attractive properties and activities against a number of protozoans causative of neglected tropical diseases. RECENT FINDINGS: This review highlights recent advances in discovery of potential treatments for human African trypanosomiasis, malaria and Chagas disease from a class of boron-containing drugs, the benzoxaboroles. SUMMARY: Research at several biotechnology companies, sponsored by product development partners (PDPs), has been successful in identifying a novel class of boron-based drugs, the benzoxaboroles, as potential treatments for neglected tropical diseases. This work was based, in part, on the earlier observation of antifungal, antibacterial and anti-inflammatory activities of the benzoxaboroles. The unique properties of boron, namely its ability to reversibly interact with biochemical targets through an empty p-orbital, are important to the success of these new drug candidates. Physicochemical and pharmacokinetic properties of the boron-based compounds are consistent with features required for oral absorption, metabolic stability and low toxicity - all important for progression of this class to clinical trials.
	PMID: 22001943 [PubMed - as supplied by publisher]

3.	Bioorg Med Chem. 2011 Sep 21. [Epub ahead of print] Pterocarpanquinones, aza-pterocarpanquinone and derivatives: Synthesis, antineoplasic activity on human malignant cell lines and antileishmanial activity on Leishmania amazonensis. Buarque CD, Militão GC, Lima DJ, Costa-Lotufo LV, Pessoa C, de Moraes MO, Cunha-Junior EF, Torres-Santos EC, Netto CD, Costa PR. Source Departamento de Química, Pontifícia Universidade Católica do Rio de Janeiro, Rua Marquês de São Vicente, 225 Gávea-Rio de Janeiro, RJ 22435-900, Brazil; Laboratório de Química Bioorgânica, Núcleo de Pesquisas de Produtos Naturais, Centro de Ciências da Saúde, Bloco H, Universidade Federal do Rio de Janeiro, RJ 21941-590, Brazil. Abstract Pterocarpanquinones (1a-e) and the aza-pterocarpanquinone (2) were synthesized through palladium catalyzed oxyarylation and azaarylation of conjugate olefins, and showed antineoplasic effect on leukemic cell lines (K562 and HL-60) as well as colon cancer (HCT-8), gliobastoma (SF-295) and melanoma (MDA-MB435) cell lines. Some derivatives were prepared (3-8) and evaluated, allowing establishing the structural requirements for the antineoplasic activity in each series. Compound 1a showed the best selectivity index in special for leukemic cells while 2 showed to be more bioselective for HCT-8, SF-295 and MDA-MB435 cells. Pterocarpanquinones 1a and 1c-e, as well as 8 were the most active on amastigote form of Leishmania amazonensis in culture. Compounds 1a, 1c and 8 showed the best selectivity index. Copyright © 2011 Elsevier Ltd. All rights reserved.
	PMID: 22000949 [PubMed - as supplied by publisher]

4.	Curr Biol. 2011 Oct 11. [Epub ahead of print] Mitochondrial Preprotein Translocase of Trypanosomatids Has a Bacterial Origin. Pusnik M, Schmidt O, Perry AJ, Oeljeklaus S, Niemann M, Warscheid B, Lithgow T, Meisinger C, Schneider A. Source Department of Chemistry and Biochemistry, University of Bern, CH-3012 Bern, Switzerland. Abstract Mitochondria are found in all eukaryotic cells and derive from a bacterial endosymbiont [1, 2]. The evolution of a protein import system was a prerequisite for the conversion of the endosymbiont into a true organelle. Tom40, the essential component of the protein translocase of the outer membrane, is conserved in mitochondria of almost all eukaryotes but lacks bacterial orthologs [3-6]. It serves as the gateway through which all mitochondrial proteins are imported. The parasitic protozoa Trypanosoma brucei and its relatives do not have a Tom40-like protein, which raises the question of how proteins are imported by their mitochondria [7, 8]. Using a combination of bioinformatics and in vivo and in vitro studies, we have discovered that T. brucei likely employs a different import channel, termed ATOM (archaic translocase of the outer mitochondrial membrane). ATOM mediates the import of nuclear-encoded proteins into mitochondria and is essential for viability of trypanosomes. It is not related to Tom40 but is instead an ortholog of a subgroup of the Omp85 protein superfamily that is involved in membrane translocation and insertion of bacterial outer membrane proteins [9]. This suggests that the protein import channel in trypanosomes is a relic of an archaic protein transport system that was operational in the ancestor of all eukaryotes. Copyright © 2011 Elsevier Ltd. All rights reserved.
	PMID: 22000100 [PubMed - as supplied by publisher]

5.	Biochemistry (Mosc). 2011 Jul;76(7):761-73. Synthetic Neoglycoconjugates of Cell-Surface Phosphoglycans of Leishmania as Potential Anti-parasite Carbohydrate Vaccines. Nikolaev AV, Sizova OV. Source College of Life Sciences, Division of Biological Chemistry and Drug Discovery, University of Dundee, Dundee DD1 5EH, UK. a.v.nikolaev@dundee.ac.uk. Abstract Leishmania are a genus of sandfly-transmitted protozoan parasites that cause a spectrum of debilitating and often fatal diseases in humans throughout the tropics and subtropics. During the parasite life cycle, Leishmania survive and proliferate in highly hostile environments. Their survival strategies involve the formation of an elaborate and dense cell-surface glycocalyx composed of diverse stage-specific glycoconjugates that form a protective barrier. Phosphoglycans constitute the variable structural and functional domain of major cell-surface lipophosphoglycan and secreted proteophosphoglycans. In this paper, we discuss structural aspects of various phosphoglycans from Leishmania with the major emphasis on the chemical preparation of neoglycoconjugates (neoglycoproteins and neoglycolipids) based on Leishmania lipophosphoglycan structures as well as the immunological evaluation for some of them as potential anti-leishmaniasis vaccines.
	PMID: 21999537 [PubMed - in process]