Gothenburg researchers make world top 10

(University of Gothenburg) As a Scientific Highlight for 2012, the journal Science has listed the top ten scientific articles published in Science and Nature during the year. Researchers Richard Neutze and Gergely Katona of the University of Gothenburg are co-authors of one of the articles, which reports on the potential for identifying new medicines for sleeping sickness using X-ray lasers to investigate the structure of proteins at atomic level.
Source: EurekAlert! - Medicine and Health - Category: Global & Universal Source Type: news

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The protozoan parasite Trypanosoma brucei is the etiological agent of human African trypanosomiasis (HAT). HAT, together with other neglected tropical diseases, causes serious health and economic issues, especially in tropical and subtropical areas. The classical antifolates targeting dihydrofolate reductase (DHFR) are ineffective towards trypanosomatid parasites owing to a metabolic bypass by the expression of pteridine reductase 1 (PTR1). The combined inhibition of PTR1 and DHFR activities in Trypanosoma parasites represents a promising strategy for the development of new effective treatments for HAT. To date, only monoc...
Source: Acta Crystallographica Section D - Category: Biochemistry Authors: Tags: Trypanosoma brucei pteridine reductase 1 antiparasitic drugs high-resolution crystal structure tricyclic compound human African trypanosomiasis research papers Source Type: research
We report here the identification spiro-containing derivatives as inhibitors of TR fromTrypanosoma brucei (TbTR), the parasite responsible for Human African Trypanosomiasis. The hit series, identified by high throughput screening, was shown to bindTbTR reversibly and to compete with the trypanothione (TS2) substrate. The prototype compound 1 from this series was also found to impede the growth ofTrypanosoma brucei parasitesin vitro. The X-ray crystal structure ofTbTR in complex with compound 1 solved at 1.98 Å allowed the identification of the hydrophobic pocket where the inhibitor binds, placed close to the catalyti...
Source: PLoS Neglected Tropical Diseases - Category: Tropical Medicine Authors: Source Type: research
Conclusions/SignificanceThe 2020 goal of HAT elimination as a public health problem is within grasp, and eligible countries are encouraged to request validation of their elimination status. Beyond 2020, the HAT community must gear up for the elimination of gambiense HAT transmission (2030 goal), by preparing for both the expected challenges (e.g. funding, coordination, integration of HAT control into regular health systems, development of more adapted tools, cryptic trypanosome reservoirs, etc.) and the unexpected ones.
Source: PLoS Neglected Tropical Diseases - Category: Tropical Medicine Authors: Source Type: research
Abstract Trypanosomiasis is a devastating neglected tropical disease affecting livestock and humans. Humans are susceptible to two Trypanosoma brucei subspecies but protected from other trypanosomes by circulating high-density lipoprotein (HDL) complexes called trypanosome lytic factors (TLFs) 1 and 2. TLFs contain apolipoprotein L-1 contributing to lysis and haptoglobin-related protein (HPR), which can function as a ligand for a parasite receptor. TLF2 also uniquely contains non-covalently associated immunoglobin M (IgM) antibodies, the role and origin of which remain unclear. Here, we show that these TLF2-associ...
Source: Cell Host and Microbe - Category: Microbiology Authors: Tags: Cell Host Microbe Source Type: research
ConclusionsThe high correlation between extinction probability and daily female adult mortality gives a strong argument that control techniques which increase daily female adult mortality may be the single most effective means of ensuring eradication of tsetse population.
Source: PLoS Neglected Tropical Diseases - Category: Tropical Medicine Authors: Source Type: research
Abstract Pactamycin and jogyamycin are aminocyclopentitol natural products, where each core carbon bears a stereodefined alcohol or amine moiety. Their structural complexity, coupled with the diversity of functional groups co-existing in a condensed space, make them fascinating synthetic targets in their own right. Pactamycin and its derivatives bind to the 30S ribosomal subunit and display activity against parasites responsible for drug-resistant malaria and African sleeping sickness; however, efforts to develop their therapeutic potential have been hampered by their cellular toxicity. Interestingly, bioengineere...
Source: Angewandte Chemie - Category: Chemistry Authors: Tags: Angew Chem Int Ed Engl Source Type: research
Trypanosomatid parasites are causative agents of important human and animal diseases such as sleeping sickness and leishmaniasis. Most trypanosomatids are transmitted to their mammalian hosts by insects, often belonging to Diptera (or true flies). With resistance to both vector-targeted pesticides and trypanocidal drugs being reported, there is a need for novel transmission blocking strategies to be developed. Studies using the blood-feeding vectors themselves are not broadly accessible, as such, new model systems are being developed to unpick insect-trypanosmatids interactions. One such case is the interactions between th...
Source: G3: Genes Genomes Genetics - Category: Genetics & Stem Cells Authors: Tags: Investigations Source Type: research
Animal African trypanosomiasis (AAT) is a life-threatening vector-borne disease, caused by trypanosome parasites, which are principally transmitted by tsetse flies. In Kenya, the prevalence of drug-resistant t...
Source: BMC Research Notes - Category: Research Authors: Tags: Research note Source Type: research
ari R Abstract In this paper, starting from the reversible rhodesain inhibitors 1a-c endowed with K i values in the low micromolar range towards the target protease, we now designed a new series of peptidomimetics 2a-g containing the benzodiazepine scaffold as a β -turn mimetic, and characterized by a specific peptide sequence for the inhibition of rhodesain. Considering that an irreversible inhibition is strongly desirable in the case of a parasitic target, a vinyl ester moiety acting as Michael-acceptor has been introduced as the warhead; finally, this portion has been functionalized in order to evaluate th...
Source: ChemMedChem - Category: Chemistry Authors: Tags: ChemMedChem Source Type: research
Abstract Trypanosomatids are unicellular parasitic protozoa. Many of the species of this genera cause severe diseases in human, such as Leishmaniasis, African trypanosomiasis and Chagas disease. These parasites possess a single reticular mitochondrion with a concatenated structure of mitochondrial DNA known as kinetoplast or kDNA. kDNA encodes few essential mitochondrial proteins but no tRNAs. Therefore, trypanosomatid mitochondrion import a full set of nucleus-encoded tRNAs for mitochondrial translation. Recent advances indicated that mitochondrial protein translocases, particularly the subunits of the ATOM compl...
Source: Gene - Category: Genetics & Stem Cells Authors: Tags: Gene Source Type: research
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