182000-09-5Relevant academic research and scientific papers
A derivative of the thiopeptide GE2270A highly selective against propionibacterium acnes
Fabbretti, Attilio,He, Cheng-Guang,Gaspari, Eleonora,Maffioli, Sonia,Brandi, Letizia,Spurio, Roberto,Sosio, Margherita,Jabes, Daniela,Donadio, Stefano
, p. 4560 - 4568 (2015)
A chemical derivative of the thiopeptide GE2270A, designated NAI003, was found to possess a substantially reduced antibacterial spectrum in comparison to the parent compound, being active against just a few Gram-positive bacteria. In particular, NAI003 retained low MICs against all tested isolates of Propionibacterium acnes and, to a lesser extent, against Enterococcus faecalis. Furthermore, NAI003 showed a time- and dose-dependent killing of both a clindamycin-resistant and a clindamycin-sensitive P. acnes isolate. Gel shift experiments indicated that, like the parent compound, NAI003 retained the ability to bind to elongation factors Tu (EF-Tus) derived from Escherichia coli, E. faecalis, or P. acnes, albeit with reduced efficiency. In contrast, EF-Tus derived from the NAI003-insensitive Staphylococcus aureus or Streptococcus pyogenes did not bind this compound. These results were confirmed by in vitro studies using a hybrid translation system, which indicated that NAI003 can inhibit most efficiently protein synthesis driven by the P. acnes EF-Tu. P. acnes mutants resistant to NAI003 were isolated by direct plating. With one exception, all analyzed strains carried mutations in the tuf gene, encoding EF-Tu. Because of its selective effect on P. acnes in comparison to resident skin flora, NAI003 represents a promising candidate for the topical treatment of acne, which has already completed a phase 1 clinical study.
Antimicrobial activities of chemically modified thiazolyl peptide antibiotic MDL 62,879 (GE2270A)
Lociuro, Sergio,Tavecchia, Paolo,Marzorati, Ettore,Landini, Paolo,Goldstein, Beth P.,Denaro, Maurizio,Ciabatti, Romeo
, p. 344 - 349 (1997)
MDL 62,879 (GE2270A) 1 is a new inhibitor of elongation factor-Tu (EF-Tu) and belongs to the class of thiazolyl peptide antibiotics. Controlled acid hydrolysis of 1 followed by treatment with base resulted in the lost of the two terminal amino acids and i
Combinatorial modification of natural products: Synthesis and in vitro analysis of derivatives of thiazole peptide antibiotic GE2270 A: A-ring modifications
Clough, Jeffrey,Chen, Shaoqing,Gordon, Eric M.,Hackbarth, Corinne,Lam, Stuart,Trias, Joaquim,White, Richard J.,Candiani, Gianpaolo,Donadio, Stefano,Romano, Gabriella,Ciabatti, Romeo,Jacobs, Jeffrey W.
, p. 3409 - 3414 (2007/10/03)
Thiazole peptide GE2270 A (1) possesses potent antimicrobial activity against many gram-positive pathogens, including methicillin resistant Staphylococcus aureus (S. aureus, MRSA; MIC90=0.06 μg/mL) and vancomycin resistant Enterococcus spp. (VRE; MIC90=0.03 μg/mL); however its poor aqueous solubility has prohibited its development for the clinical treatment of infections. An integrated combinatorial and medicinal chemistry program was employed to identify derivatives of 1 that retain activity but possess greatly enhanced aqueous solubility.
