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解决方案
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Resistance to a Protein Farnesyltransfer
发布:深圳市朗诚科技股份有限公司浏览次数:420The post-translational farnesylation of proteins serves to anchor a subset of intracellular proteins to membranes in eukaryotic organisms and also promotes protein-protein interactions. Inhibition of protein farnesyltransferase (PFT) is lethal to the pathogenic protozoa Plasmodium falciparum. Parasites were isolated that were resistant to BMS-388891, a tetrahydroquinoline (THQ) PFT inhibitor. Resistance was associated with a 12-fold decrease in drug susceptibility. Genotypic analysis revealed a single point mutation in the subunit in resistant parasites. The resultant tyrosine 837 to cysteine alteration in the subunit corresponded to the binding site for the THQ and peptide substrate. Biochemical analysis of Y837C-PFT demonstrated a 13-fold increase in BMS-388891 concentration necessary for inhibiting 50% of the enzyme activity. These data are consistent with PFT as the target of BMS-388891 in P. falciparum and suggest that PFT inhibitors 首ld be combined with other antimalarial agents for effective therapy. TSI激光粒子计数器/尘埃粒子计数器/激光尘埃粒子计数器
2006-12-27相关仪器 -
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