2012
DOI: 10.1016/j.ijpara.2011.11.008
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Dual targeting of aminoacyl-tRNA synthetases to the apicoplast and cytosol in Plasmodium falciparum

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Cited by 66 publications
(85 citation statements)
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“…ability of the three top-ranked borrelidin analogs (BC194, BC196, and BC220), based on the in vivo results, to inhibit the aminoacylation reaction of both P. falciparum and human ThrRS. P. falciparum encodes a single ThrRS that acts both in the cytosol and the apicoplast (28). In contrast, human cells encode two distinct ThrRSs that act separately in the cytosol and the mitochondria.…”
Section: Resultsmentioning
confidence: 99%
See 1 more Smart Citation
“…ability of the three top-ranked borrelidin analogs (BC194, BC196, and BC220), based on the in vivo results, to inhibit the aminoacylation reaction of both P. falciparum and human ThrRS. P. falciparum encodes a single ThrRS that acts both in the cytosol and the apicoplast (28). In contrast, human cells encode two distinct ThrRSs that act separately in the cytosol and the mitochondria.…”
Section: Resultsmentioning
confidence: 99%
“…Borrelidin is a noncompetitive inhibitor of both bacterial and eukaryotic threonyl-tRNA synthetases (ThrRS) (23) and exhibits antiangiogenic (24)(25)(26), antimalarial (21,22), and antimicrobial (27) properties. The antimalarial activity of borrelidin is thought to arise from inhibition of ThrRS, which in Plasmodium, is present as a single enzyme dually targeted to cytosol and apicoplast (28). However, its high cytotoxicity in humans limits its use (29).…”
Section: Significancementioning
confidence: 99%
“…Recently, dual-targeting delivery has been widely developed and played an important role in a variety of areas (Alpizar et al, 2011;Petkau et al, 2011;Yogev et al, 2011;Jackson et al, 2012), including cancer therapy (Shao et al, 2012;Xu et al, 2012). Which primary usually delivered anticancer drug to the diseased tissue, then to the tumors with some targeting moieties (Petkau et al, 2011).…”
Section: Introductionmentioning
confidence: 99%
“…Alanyl-, glycyl-, cysteinyl-and threonyl-tRNA synthetases (AlaRS, GlyRS, CysRS and ThrRS) are especially interesting potential targets due to their dual localization. [26][27][28] The natural macrolide antibiotic borrelidin was first isolated from Streptomyces rocheii in 1949, and its potent inhibitory activity against bacterial growth was later linked to ThrRS inhibition. 29 Borrelidin was more recently recovered from a largescale screen of soil microorganism-derived substances for its ability to block malaria parasite growth in vitro and in vivo.…”
mentioning
confidence: 99%
“…Genomic and immunohistochemical evidence suggests that ThrRS is simultaneously targeted to both the cytoplasm and the apicoplast. 26 Jackson et al 27 showed that ThrRS is expressed throughout parasite blood-stage sexual development, and that borrelidin causes a rapid arrest of parasitic growth. Borrelidin is more active than mupirocin, which specifically targets the apicoplastic but not cytoplasmic IleRS isozyme, leading to the 'delayed death' phenotype associated with inhibitors of crucial apicoplast enzymes in plasmodium species.…”
mentioning
confidence: 99%