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Rufomycin Targets ClpC1 Proteolysis in Mycobacterium tuberculosis and M. abscessus.

Antimicrob. Agents Chemother.. 2019; 
ChoulesMary P,WolfNina M,LeeHyun,AndersonJeffrey R,GrzelakEdyta M,WangYuehong,MaRui,GaoWei,McAlpineJames B,JinYing-Yu,ChengJinhua,LeeHanki,SuhJoo-Won,DucNguyen Minh,PaikSeungwha,ChoeJin Ho,JoEun-Kyeong,ChangChulhun L,LeeJong Seok,JakiBirgit U,PauliGuido F,FranzblauScott G,ChoSang
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Mutagenesis Services M. abscessus and M. chelonae ClpC1 plasmids were obtained from Genscript (Piscataway, NJ) using M. tuberculosis clpC2 as a DNA template for mutagenesis. Get A Quote

摘要

ClpC1 is an emerging new target for the treatment of infections, and several cyclic peptides (ecumicin, cyclomarin A, and lassomycin) are known to act on this target. This study identified another group of peptides, the rufomycins (RUFs), as bactericidal to through the inhibition of ClpC1 and subsequent modulation of protein degradation of intracellular proteins. Rufomycin I (RUFI) was found to be a potent and selective lead compound for both (MIC, 0.02 μM) and (MIC, 0.4 μM). Spontaneously generated mutants resistant to RUFI involved seven unique single nucleotide polymorphism (SNP) mutations at three distinct codons within the -terminal domain of (V13, H77, and F80). RUFI also sign... More

关键词

ClpC1,Mycobacterium abscessus,Mycobacterium tuberculosis,cyclic peptide,rufom