A5078464342- Trypanosoma species research and implications
- Biochemical and Molecular Research
- Research on Leishmaniasis Studies
- HIV/AIDS drug development and treatment
- Calcium signaling and nucleotide metabolism
- Carbohydrate Chemistry and Synthesis
- Toxin Mechanisms and Immunotoxins
- DNA Repair Mechanisms
- Cancer therapeutics and mechanisms
- CRISPR and Genetic Engineering
- Synthesis and biological activity
- Helminth infection and control
- Plant biochemistry and biosynthesis
- Insect-Plant Interactions and Control
- Malaria Research and Control
- Glycosylation and Glycoproteins Research
- Bioactive Compounds and Antitumor Agents
- Cytomegalovirus and herpesvirus research
- Parasitic Infections and Diagnostics
- Plant Virus Research Studies
Instituto de Parasitología y Biomedicina "López - Neyra"
2008-2023
Consejo Superior de Investigaciones Científicas
2012-2023
Parque Tecnológico de la Salud
2006
A series of azasterol derivatives, designed as potential inhibitors the Delta(24)-sterol methyltransferase enzyme (24-SMT), were synthesized and evaluated for their activities against parasitic protozoa. Values in nanomolar range obtained 50% effective dose Trypanosoma brucei subsp. rhodesiense bloodstream form cultured vitro. In order to investigate mode action, 24-SMT was cloned overexpressed compounds assayed inhibitory activity. None tested appeared be active enzyme. Sterol composition...
DNA single-strand breaks containing 3′-blocking groups are generated from attack of the sugar backbone by reactive oxygen species or after base excision glycosylase/apurinic/apyrimidinic (AP) lyases. In human cells, APE1 excises fragments that block 3′-ends thus facilitating repair synthesis. Leishmania major, causal agent leishmaniasis, homolog is class II AP endonuclease LMAP. Expression LMAP but not reverts hypersensitivity a xth nfo repair-deficient Escherichia coli strain to oxidative...
Current treatments available for African sleeping sickness or human trypanosomiasis (HAT) are limited, with poor efficacy and unacceptable safety profiles. Here, we report a new approach to address treatment of this disease based on the use compounds that bind parasite surface glycans leading rapid killing trypanosomes. Pradimicin its derivatives non-peptidic carbohydrate-binding agents adhere carbohydrate moiety glycoproteins inducing lysis in vitro. Notably, pradimicin S has good...
Thymidine kinase (TK) is a key enzyme in the pyrimidine salvage pathway which catalyzes transfer of γ-phosphate ATP to 2'-deoxythymidine (dThd) forming thymidine monophosphate (dTMP). Unlike other type II TKs, Trypanosoma brucei (TbTK) tandem protein with two TK homolog domains only C-terminal one active. In this study, we establish that TbTK essential for parasite viability and cell cycle progression, independently extracellular concentrations. We show expression regulated depletion leads...
Trypanosoma brucei variant surface glycoproteins (VSG) are glycosylated by both paucimannose and oligomannose structures which involved in the formation of a protective barrier against immune system. Here, we report that stinging nettle lectin (UDA), with predominant N-acetylglucosamine-binding specificity, interacts VSGs kills parasites provoking defects endocytosis together impaired cytokinesis. Prolonged exposure to UDA induced parasite resistance based on diminished capacity bind due an...
Maintenance of dNTPs pools in Trypanosoma brucei is dependent on both biosynthetic and degradation pathways that together ensure correct cellular homeostasis throughout the cell cycle which essential for preservation genomic stability. Both salvage de novo participate provision pyrimidine while purine are made available solely through salvage. In order to identify enzymes involved here we have characterized role a trypanosomal SAMHD1 orthologue denominated TbHD82. Our results show TbHD82...
The surface of Trypanosoma brucei is covered by a dense coat glycosylphosphatidylinositol-anchored glycoproteins. major component the variant glycoprotein (VSG) which glycosylated both paucimannose and oligomannose N-glycans. Surface glycans are poorly accessible killing mediated peptide lectin-VSG complexes hindered active endocytosis. However, contrary to previous observations, here we show that high-affinity carbohydrate binding agents bind glycoproteins abrogate growth T. bloodstream...
The maintenance of deoxyribonucleotide triphosphate (dNTP) homeostasis through synthesis and degradation is critical for accurate genomic mitochondrial DNA replication fidelity. Trypanosoma brucei makes use both the salvage de novo pathways provision pyrimidine dNTPs. In this respect, sterile α motif histidine-aspartate domain-containing protein 1 (SAMHD1) appears to be most relevant dNTPase controlling dNTP/deoxynucleoside in mammalian cells. Here, we have characterized role a unique...
Cytidine deaminase (CDA) is a pyrimidine salvage enzyme that catalyzes cytidine and deoxycytidine hydrolytic deamination to yield uridine deoxyuridine. Here we report the biochemical characterization of Trypanosoma brucei CDA as an within tetrameric class family efficiently deaminates cytidine, deoxycytidine, nucleoside analogue 5-methyl-2'-deoxycytidine. In line with previous studies, show RNA interference (RNAi)-mediated depletion impairs T. proliferation when grown in pyrimidine-deficient...