Naslov
Antibacterial Properties of Metallocenyl-7-ADCA Derivatives and Structure in Complex with CTX-M beta-Lactamase
(Antibacterial Properties of Metallocenyl-7-ADCA Derivatives and Structure in Complex with CTX-M β-Lactamase)

Autori
Lewandowski, Eric ; Szczupak, Lukasz ; Wong, Stephanie ; Skiba, Joanna ; Guspiel, Adam ; Solecka, Jolanta ; Vrček, Valerije ; Kowalski, Konrad ; Chen, Yu

Izvornik
Organometallics (0276-7333) 36 (2017), 9; 1673-1676

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
organometallic chemistry ; electrochemistry ; bioactive compounds ; reaction mechanism

Sažetak
A series of six novel metallocenyl-7-ADCA (metallocenyl = ferrocenyl or ruthenocenyl ; 7-ADCA = 7-aminodesacetoxycephalosporanic acid) conjugates were synthesized and their antibacterial properties evaluated by biochemical and microbiological assays. The ruthenocene derivatives showed a higher level of inhibition of dd-carboxypeptidase 64-575, a penicillin binding protein (PBP), than the ferrocene derivatives and the reference compound penicillin G. Protein X-ray crystallographic analysis revealed a covalent acyl–enzyme complex of a ruthenocenyl compound with CTX-M β-lactamase E166A mutant, corresponding to a similar complex with PBPs responsible for the bactericidal activities of these compounds. Most interestingly, an intact compound was captured at the crystal-packing interface, elucidating for the first time the structure of a metallocenyl β-lactam compound that previously eluded small-molecule crystallography. We propose that protein crystals, even from biologically unrelated molecules, can be utilized to determine structures of small molecules.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

Napomena
DOI: 10.1021/acs.organomet.6b00888 ; Publication Date (Web): February 1, 2017.

POVEZANOST RADA