Inhibition of Trypanosoma brucei brucei peptidyl transferase activity by sparsomycin analogs and effects on trypanosome protein synthesis and proliferation

1985 ◽  
Vol 34 (17) ◽  
pp. 3055-3060 ◽  
Author(s):  
Alan J. Bitonti ◽  
Susan E. Kelly ◽  
Gary A. Flynn ◽  
Peter P. McCann
Keyword(s):  
Protein Synthesis ◽  
Trypanosoma Brucei ◽  
Transferase Activity ◽  
Peptidyl Transferase ◽  
Trypanosoma Brucei Brucei

Characterization of a High-Throughput Screening Assay for Inhibitors of Elongation Factor P and Ribosomal Peptidyl Transferase Activity

2006 ◽  
Vol 11 (7) ◽  
pp. 736-742 ◽  
Author(s):  
Steven Swaney ◽  
Mark McCroskey ◽  
Dean Shinabarger ◽  
Zhigang Wang ◽  
Benjamin A. Turner ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
High Throughput Screening ◽  
Elongation Factor ◽  
Peptide Bond ◽  
Transferase Activity ◽  
Reaction Products ◽  
Peptidyl Transferase ◽  
Screening Assay ◽  
High Throughput Screening Assay ◽  
Elongation Factor P

Elongation Factor P (EF-P) is an essential component of bacterial protein synthesis, enhancing the rate of translation by facilitating the addition of amino acids to the growing peptide chain. Using purified Staphylococcus aureus EF-P and a reconstituted Escherichia coli ribosomal system, an assay monitoring the addition of radiolabeled N-formyl methionine to biotinylated puromycin was developed. Reaction products were captured with streptavidin-coated scintillation proximity assay (SPA) beads and quantified by scintillation counting. Data from the assay were used to create a kinetic model of the reaction scheme. In this model, EF-P binding to the ribosome essentially doubled the rate of the ribosomal peptidyl transferase reaction. As described here, EF-P bound to the ribosomes with an apparent Ka of 0.75 μM, and the substrates N-fMet-tRNA and biotinylated puromycin had apparent Kms of 19 μM and 0.5 μM, respectively. The assay was shown to be sensitive to a number of antibiotics known to target ribosomal peptide bond synthesis, such as chloramphenicol and puromycin, but not inhibitors that target other stages of protein synthesis, such as fusidic acid or thiostrepton.

scholarly journals Effects of α-difluoromethylornithine on protein synthesis and synthesis of the variant-specific glycoprotein (VSG) in Trypanosoma brucei brucei

1988 ◽  
Vol 250 (1) ◽  
pp. 295-298 ◽  
Author(s):  
A J Bitonti ◽  
D E Cross-Doersen ◽  
P P McCann
Keyword(s):  
Protein Synthesis ◽  
Trypanosoma Brucei ◽  
Mechanism Of Action ◽  
Myristic Acid ◽  
Leucine Incorporation ◽  
Biochemical Mechanism ◽  
Trypanosoma Brucei Brucei ◽  
Apparent Decrease

Protein synthesis in Trypanosoma brucei brucei was rapidly inhibited during polyamine depletion by DL-alpha-difluoromethylornithine (DFMO) in vitro and in vivo. [3H]Leucine incorporation was depressed 30-40% by 24 h and 80-90% by 48 h of DFMO treatment. Concomitantly there was an apparent decrease in the synthesis of the variant-specific glycoprotein (VSG) in DFMO-treated trypanosomes, as measured by decreased incorporation of [3H]myristic acid into VSG. The discovery of decreased protein synthesis in T. b. brucei during DFMO treatment is noteworthy, because it was reported previously that protein synthesis was paradoxically stimulated 2-4-fold during DFMO treatment in these organisms. Decreased protein synthesis probably relates to the biochemical mechanism of action of DFMO on trypanosomes.

Effects of n-hexane and ethylacetate fractions of Terminalia catappa leaf extract in experimental Trypanosoma brucei brucei infection in Wistar rats

2021 ◽  
Author(s):  
Folashade Sarah Ojeleye ◽  
Helen Ileigo Inabo ◽  
Clement Myah Zaman Whong ◽  
Bolanle Olufunke Priscilla Musa ◽  
Ochuko Orakpoghenor
Keyword(s):  
Trypanosoma Brucei ◽  
Wistar Rats ◽  
Leaf Extract ◽  
Trypanosoma Brucei Brucei ◽  
Terminalia Catappa

Modulation of Early Immune Responses and Suppression of Trypanosoma brucei brucei Infections by Surgical Denervation of the Spleen

2000 ◽  
Vol 8 (1) ◽  
pp. 31-38 ◽  
Author(s):  
Yajuan Liu ◽  
Manal Mustafa ◽  
Hu-Lun Li ◽  
Lauri Nuortio ◽  
Amged Mustafa ◽  
...  
Keyword(s):  
Immune Responses ◽  
Trypanosoma Brucei ◽  
Trypanosoma Brucei Brucei
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