Antibacterial Properties of Metallocenyl-7-ADCA Derivatives and Structure in Complex with CTX-M β-Lactamase
Document Type
Article
Publication Date
2017
Digital Object Identifier (DOI)
https://doi.org/10.1021/acs.organomet.6b00888
Abstract
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.
Was this content written or created while at USF?
Yes
Citation / Publisher Attribution
Organometallics, v. 36, issue 9, p. 1673-1676
Scholar Commons Citation
Lewandowski, Eric M.; Szczupak, Łukasz; Wong, Stephanie; Skiba, Joanna; Guśpiel, Adam; Solecka, Jolanta; Vrček, Valerije; Kowalski, Konrad; and Chen, Yu, "Antibacterial Properties of Metallocenyl-7-ADCA Derivatives and Structure in Complex with CTX-M β-Lactamase" (2017). Molecular Medicine Faculty Publications. 106.
https://digitalcommons.usf.edu/mme_facpub/106
