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New noncovalent inhibitors of penicillin-binding proteins from penicillin-resistant bacteria
Turk, Samo (Avtor), Verlaine, Olivier (Avtor), Gerards, Thomas (Avtor), Živec, Matej (Avtor), Humljan, Jan (Avtor), Sosič, Izidor (Avtor), Amoroso, Ana (Avtor), Zervosen, Astrid (Avtor), Luxen, André (Avtor), Joris, Bernard (Avtor), Gobec, Stanislav (Avtor)

URLURL - Predstavitvena datoteka, za dostop obiščite http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0019418 Novo okno

Izvleček
Background: Penicillin-binding proteins (PBPs) are well known and validated targets for antibacterial therapy. The most important clinically used inhibitors of PBPs ß-lactams inhibit transpeptidase activity of PBPs by forming a covalent penicilloyl-enzyme complex that blocks the normal transpeptidation reaction; this finally results in bacterial death. In some resistant bacteria the resistance is acquired by active-site distortion of PBPs, which lowers their acylation efficiency for ?-lactams. To address this problem we focused our attention to discovery of novel noncovalent inhibitors of PBPs. Methodology/Principal Findings Our in-house bank of compounds was screened for inhibition of three PBPs from resistant bacteria: PBP2a from Methicillin-resistant Staphylococcus aureus (MRSA), PBP2x from Streptococcus pneumoniae strain 5204, and PBP5fm from Enterococcus faecium strain D63r. Initial hit inhibitor obtained by screening was then used as a starting point for computational similarity searching for structurally related compounds and several new noncovalent inhibitors were discovered. Two compounds had promising inhibitory activities of both PBP2a and PBP2x 5204, and good in-vitro antibacterial activities against a panel of Gram-positive bacterial strains. Conclusions We found new noncovalent inhibitors of PBPs which represent important starting points for development of more potent inhibitors of PBPs that can target penicillin-resistant bacteria.

Jezik:Angleški jezik
Ključne besede:non-kovalentni inhibitorji, proteini, PBP2a
Vrsta gradiva:Delo ni kategorizirano (r6)
Tipologija:1.01 - Izvirni znanstveni članek
Organizacija:FFA - Fakulteta za farmacijo
Leto izida:2011
Št. strani:10 str.
Številčenje:Vol. 6, no. 5
UDK:543
ISSN pri članku:1932-6203
COBISS.SI-ID:3007857 Povezava se odpre v novem oknu
Število ogledov:534
Število prenosov:156
Metapodatki:XML RDF-CHPDL DC-XML DC-RDF
 
Skupna ocena:(0 glasov)
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Gradivo je del revije

Naslov:PloS one
Založnik:Public Library of Science
COBISS.SI-ID:2005896 Novo okno

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