Mostrar el registro sencillo del ítem

dc.creatorKostopoulou, O. N.en
dc.creatorMagoulas, G. E.en
dc.creatorPapadopoulos, G. E.en
dc.creatorMouzaki, A.en
dc.creatorDinos, G. P.en
dc.creatorPapaioannou, D.en
dc.creatorKalpaxis, D. L.en
dc.date.accessioned2015-11-23T10:35:48Z
dc.date.available2015-11-23T10:35:48Z
dc.date.issued2015
dc.identifier10.1371/journal.pone.0134526
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/11615/29700
dc.description.abstractAs fight against antibiotic resistance must be strengthened, improving old drugs that have fallen in reduced clinical use because of toxic side effects and/or frequently reported resistance, like chloramphenicol (CAM), is of special interest. Chloramphenicol (CAM), a prototypical wide-spectrum antibiotic has been shown to obstruct protein synthesis via binding to the bacterial ribosome. In this study we sought to identify features intensifying the bacteriostatic action of CAM. Accordingly, we synthesized a series of CAM-dimers with various linker lengths and functionalities and compared their efficiency in inhibiting peptide-bond formation in an Escherichia coli cell-free system. Several CAM-dimers exhibited higher activity, when compared to CAM. The most potent of them, compound 5, containing two CAM bases conjugated via a dicarboxyl aromatic linker of six successive carbon-bonds, was found to simultaneously bind both the ribosomal catalytic center and the exit-tunnel, thus revealing a second, kinetically cryptic binding site for CAM. Compared to CAM, compound 5 exhibited comparable antibacterial activity against MRSA or wild-type strains of Staphylococcus aureus, Enterococcus faecium and E. coli, but intriguingly superior activity against some CAM-resistant E. coli and Pseudomonas aeruginosa strains. Furthermore, it was almost twice as active in inhibiting the growth of T-leukemic cells, without affecting the viability of normal human lymphocytes. The observed effects were rationalized by footprinting tests, crosslinking analysis, and MD-simulations.en
dc.source.uri<Go to ISI>://WOS:000359492300049
dc.subject23S RIBOSOMAL-RNAen
dc.subjectPEPTIDYL TRANSFERASE CENTERen
dc.subjectESCHERICHIA-COLIen
dc.subjectRIBOSOMESen
dc.subjectMULTIDRUG EFFLUX PUMPen
dc.subjectANTIBIOTIC-RESISTANCEen
dc.subjectNASCENTen
dc.subjectPEPTIDEen
dc.subjectBINDING-SITEen
dc.subjectIN-VIVOen
dc.subjectINHIBITIONen
dc.subjectPEPTIDYLTRANSFERASEen
dc.subjectMultidisciplinary Sciencesen
dc.titleSynthesis and Evaluation of Chloramphenicol Homodimers: Molecular Target, Antimicrobial Activity, and Toxicity against Human Cellsen
dc.typejournalArticleen


Ficheros en el ítem

FicherosTamañoFormatoVer

No hay ficheros asociados a este ítem.

Este ítem aparece en la(s) siguiente(s) colección(ones)

Mostrar el registro sencillo del ítem