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

Lewandowski, Eric M.; Szczupak, Łukasz; Wong, Stephanie; Skiba, Joanna; Guśpiel, Adam; Solecka, Jolanta; Vrček, Valerije; Kowalski, Konrad; Chen, Yu

doi:10.1021/acs.organomet.6b00888

Title: Antibacterial Properties of Metallocenyl-7-ADCA Derivatives and Structure in Complex with CTX-M β-Lactamase

Journal Article · Wed Feb 01 00:00:00 EST 2017 · Organometallics

DOI:https://doi.org/10.1021/acs.organomet.6b00888· OSTI ID:1463718

Lewandowski, Eric M. ^[1]; Szczupak, Łukasz ^[2]; Wong, Stephanie ^[1]; Skiba, Joanna ^[2]; Guśpiel, Adam ^[3]; Solecka, Jolanta ^[3];

^[4]; Kowalski, Konrad ^[2];

^[1]

Univ. of South Florida, Tampa, FL (United States). Morsani College of Medicine
Univ. of Łódź, Tamka (Poland)
National Inst. of Public Health - National Inst. of Hygiene (NIPH-NIH), Warsaw (Poland)
Univ. of Zagreb (Croatia)

We report 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 DDcarboxypeptidase 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.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: National Institutes of Health (NIH); National Science Centre of Poland (NCN)

Grant/Contract Number:: DEC-2013/11/B/ ST5/00997

OSTI ID:: 1463718

Journal Information:: Organometallics, Vol. 36, Issue 9; ISSN 0276-7333

Publisher:: American Chemical SocietyCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Cited by: 36 works

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References (46)

beta-Lactamases in laboratory and clinical resistance. Livermore, D. M. Clinical Microbiology Reviews, Vol. 8, Issue 4 https://doi.org/10.1128/CMR.8.4.557	journal	October 1995
Atomic Resolution Structures of CTX-M β-Lactamases: Extended Spectrum Activities from Increased Mobility and Decreased Stability Chen, Yu; Delmas, Julien; Sirot, Jacques Journal of Molecular Biology, Vol. 348, Issue 2 https://doi.org/10.1016/j.jmb.2005.02.010	journal	April 2005
Zinc as a Cofactor for Cephalosporinase from Bacillus cereus 569 Sabath, L. D.; Abraham, E. P. Biochemical Journal, Vol. 98, Issue 1 https://doi.org/10.1042/bj0980011C	journal	January 1966
Molecular basis of antibiotic resistance and β-lactamase inhibition by mechanism-based inactivators: perspectives and future directions Therrien, Christian; Levesque, Roger C. FEMS Microbiology Reviews, Vol. 24, Issue 3 https://doi.org/10.1111/j.1574-6976.2000.tb00541.x	journal	July 2000
Molecular Basis for the Catalytic Specificity of the CTX-M Extended-Spectrum β-Lactamases Adamski, Carolyn J.; Cardenas, Ana Maria; Brown, Nicholas G. Biochemistry, Vol. 54, Issue 2 https://doi.org/10.1021/bi501195g	journal	December 2014
Structural Analysis of the Role of Pseudomonas aeruginosa Penicillin-Binding Protein 5 in β-Lactam Resistance Smith, Jeffrey D.; Kumarasiri, Malika; Zhang, Weilie Antimicrobial Agents and Chemotherapy, Vol. 57, Issue 7 https://doi.org/10.1128/AAC.00505-13	journal	April 2013
Enzyme crystal structure in a neat organic solvent. Fitzpatrick, P. A.; Steinmetz, A. C.; Ringe, D. Proceedings of the National Academy of Sciences, Vol. 90, Issue 18 https://doi.org/10.1073/pnas.90.18.8653	journal	September 1993
Extended-Spectrum -Lactamases in the 21st Century: Characterization, Epidemiology, and Detection of This Important Resistance Threat Bradford, P. A. Clinical Microbiology Reviews, Vol. 14, Issue 4 https://doi.org/10.1128/CMR.14.4.933-951.2001	journal	October 2001
Intermolecular hydrogen bonds with d-electrons of transition metal atoms. H-complexes with metallocenes of the iron subgroup Shubina, E. S.; Krylov, A. N.; Kreindlin, A. Z. Journal of Molecular Structure, Vol. 301 https://doi.org/10.1016/0022-2860(93)80225-K	journal	December 1993
Distinct Single-Cell Morphological Dynamics under Beta-Lactam Antibiotics Yao, Zhizhong; Kahne, Daniel; Kishony, Roy Molecular Cell, Vol. 48, Issue 5 https://doi.org/10.1016/j.molcel.2012.09.016	journal	December 2012
Locating interaction sites on proteins: The crystal structure of thermolysin soaked in 2% to 100% isopropanol English, Andrew C.; Done, Sarah H.; Caves, Leo S. D. Proteins: Structure, Function, and Genetics, Vol. 37, Issue 4 https://doi.org/10.1002/(SICI)1097-0134(19991201)37:4<628::AID-PROT13>3.0.CO;2-G	journal	December 1999
A new class of semi-synthetic antibiotics: ferrocenyl-penicillins and -cephalosporins Edwards, Eve I.; Epton, Roger; Marr, George Journal of Organometallic Chemistry, Vol. 107, Issue 3 https://doi.org/10.1016/S0022-328X(00)91527-4	journal	March 1976
Challenges and Opportunities in the Development of Organometallic Anticancer Drugs Hartinger, Christian G.; Metzler-Nolte, Nils; Dyson, Paul J. Organometallics, Vol. 31, Issue 16 https://doi.org/10.1021/om300373t	journal	July 2012
The penicillin-binding proteins: structure and role in peptidoglycan biosynthesis Sauvage, Eric; Kerff, Frédéric; Terrak, Mohammed FEMS Microbiology Reviews, Vol. 32, Issue 2 https://doi.org/10.1111/j.1574-6976.2008.00105.x	journal	March 2008
Three Decades of -Lactamase Inhibitors Drawz, S. M.; Bonomo, R. A. Clinical Microbiology Reviews, Vol. 23, Issue 1 https://doi.org/10.1128/CMR.00037-09	journal	January 2010
The future of the β-lactams Llarrull, Leticia I.; Testero, Sebastian A.; Fisher, Jed F. Current Opinion in Microbiology, Vol. 13, Issue 5 https://doi.org/10.1016/j.mib.2010.09.008	journal	October 2010
Hydrogen-bonded complexes involving the metal atom and protonation of metallocenes of the iron subgroup Shubina, E. S.; Krylov, A. N.; Kreindlin, A. Z. Journal of Organometallic Chemistry, Vol. 465, Issue 1-2 https://doi.org/10.1016/0022-328X(94)87063-2	journal	February 1994
Metallo-β-lactamases (classification, activity, genetic organization, structure, zinc coordination) and their superfamily Bebrone, Carine Biochemical Pharmacology, Vol. 74, Issue 12 https://doi.org/10.1016/j.bcp.2007.05.021	journal	December 2007
The Bacteria Fight Back Taubes, G. Science, Vol. 321, Issue 5887 https://doi.org/10.1126/science.321.5887.356	journal	July 2008
Synthesis and Biological Evaluation of Ferrocene-Containing Bioorganometallics Inspired by the Antibiotic Platensimycin Lead Structure Patra, Malay; Gasser, Gilles; Wenzel, Michaela Organometallics, Vol. 29, Issue 19 https://doi.org/10.1021/om100614c	journal	October 2010
X-ray analysis on the nanogram to microgram scale using porous complexes Inokuma, Yasuhide; Yoshioka, Shota; Ariyoshi, Junko Nature, Vol. 495, Issue 7442 https://doi.org/10.1038/nature11990	journal	March 2013
Ferrocifen type anti cancer drugs Jaouen, Gérard; Vessières, Anne; Top, Siden Chemical Society Reviews, Vol. 44, Issue 24 https://doi.org/10.1039/C5CS00486A	journal	January 2015
Resistance to antibiotics targeted to the bacterial cell wall: The Bacterial Cell Wall as a Target for Antibiotics Nikolaidis, I.; Favini-Stabile, S.; Dessen, A. Protein Science, Vol. 23, Issue 3 https://doi.org/10.1002/pro.2414	journal	January 2014
Ferrocenyl bioconjugates of ampicillin and 6-aminopenicillinic acid – Synthesis, electrochemistry and biological activity Skiba, Joanna; Rajnisz, Aleksandra; de Oliveira, Kely Navakoski European Journal of Medicinal Chemistry, Vol. 57 https://doi.org/10.1016/j.ejmech.2012.09.023	journal	November 2012
Small organometallic compounds as antibacterial agents Patra, Malay; Gasser, Gilles; Metzler-Nolte, Nils Dalton Transactions, Vol. 41, Issue 21 https://doi.org/10.1039/c2dt12460b	journal	January 2012
Metallocene-Modified Uracils: Synthesis, Structure, and Biological Activity Kowalski, Konrad; Skiba, Joanna; Oehninger, Luciano Organometallics, Vol. 32, Issue 20 https://doi.org/10.1021/om400294s	journal	May 2013
Epidemiological Expansion, Structural Studies, and Clinical Challenges of New β-Lactamases from Gram-Negative Bacteria Bush, Karen; Fisher, Jed F. Annual Review of Microbiology, Vol. 65, Issue 1 https://doi.org/10.1146/annurev-micro-090110-102911	journal	October 2011
Getting to the route of Helicobacter pylori treatment Goddard, A. Journal of Antimicrobial Chemotherapy, Vol. 42, Issue 1 https://doi.org/10.1093/jac/42.1.1	journal	July 1998
Growing Group of Extended-Spectrum -Lactamases: the CTX-M Enzymes Bonnet, R. Antimicrobial Agents and Chemotherapy, Vol. 48, Issue 1 https://doi.org/10.1128/AAC.48.1.1-14.2004	journal	December 2003
Intermolecular Cross Linking of a Protein in the Crystalline State: Carboxypeptidase-A Quiocho, F. A.; Richards, F. M. Proceedings of the National Academy of Sciences, Vol. 52, Issue 3 https://doi.org/10.1073/pnas.52.3.833	journal	September 1964
Multiple Solvent Crystal Structures: Probing Binding Sites, Plasticity and Hydration Mattos, Carla; Bellamacina, Cornelia R.; Peisach, Ezra Journal of Molecular Biology, Vol. 357, Issue 5 https://doi.org/10.1016/j.jmb.2006.01.039	journal	April 2006
Highly active antibacterial ferrocenoylated or ruthenocenoylated Arg-Trp peptides can be discovered by an l -to- d substitution scan Albada, H. Bauke; Prochnow, Pascal; Bobersky, Sandra Chem. Sci., Vol. 5, Issue 11 https://doi.org/10.1039/C4SC01822B	journal	January 2014
Metallo-β-lactamase structure and function: Metallo-β-lactamase structure and function Palzkill, Timothy Annals of the New York Academy of Sciences, Vol. 1277, Issue 1 https://doi.org/10.1111/j.1749-6632.2012.06796.x	journal	November 2012
Separation, purification and properties of β-lactamase I and β-lactamase II from Bacillus cereus 569/H/9 Davies, Richard B.; Abraham, E. P.; Melling, J. Biochemical Journal, Vol. 143, Issue 1 https://doi.org/10.1042/bj1430115	journal	October 1974
The Acylation Mechanism of CTX-M β-Lactamase at 0.88 Å Resolution Chen, Yu; Bonnet, Richard; Shoichet, Brian K. Journal of the American Chemical Society, Vol. 129, Issue 17 https://doi.org/10.1021/ja0712064	journal	May 2007
Structural Insights into Substrate Recognition and Product Expulsion in CTX-M Enzymes Delmas, Julien; Leyssene, David; Dubois, Damien Journal of Molecular Biology, Vol. 400, Issue 1 https://doi.org/10.1016/j.jmb.2010.04.062	journal	July 2010
Synthesis, characterization and antibacterial activities of some new ferrocene-containing penems Long, Bohua; He, Chunlian; Yang, Yingbin European Journal of Medicinal Chemistry, Vol. 45, Issue 3 https://doi.org/10.1016/j.ejmech.2009.12.045	journal	March 2010
A functional classification scheme for beta-lactamases and its correlation with molecular structure Bush, K.; Jacoby, G. A.; Medeiros, A. A. Antimicrobial Agents and Chemotherapy, Vol. 39, Issue 6 https://doi.org/10.1128/AAC.39.6.1211	journal	June 1995
Streptomycetes excreting dd-carboxypeptidases Kurzątkowski, W.; Solecka, J.; Filipek, J. Applied Microbiology and Biotechnology, Vol. 33, Issue 4 https://doi.org/10.1007/BF00176664	journal	July 1990
Structure, Function, and Inhibition along the Reaction Coordinate of CTX-M β-Lactamases Chen, Yu; Shoichet, Brian; Bonnet, Richard Journal of the American Chemical Society, Vol. 127, Issue 15 https://doi.org/10.1021/ja042850a	journal	April 2005
Organometallic Anticancer Compounds Gasser, Gilles; Ott, Ingo; Metzler-Nolte, Nils Journal of Medicinal Chemistry, Vol. 54, Issue 1 https://doi.org/10.1021/jm100020w	journal	January 2011
Application of ferrocene and its derivatives in cancer research Ornelas, Cátia New Journal of Chemistry, Vol. 35, Issue 10 https://doi.org/10.1039/c1nj20172g	journal	January 2011
Antibacterial properties and atomic resolution X-ray complex crystal structure of a ruthenocene conjugated β-lactam antibiotic Lewandowski, Eric M.; Skiba, Joanna; Torelli, Nicholas J. Chemical Communications, Vol. 51, Issue 28 https://doi.org/10.1039/C5CC00904A	journal	January 2015
Penicillin Binding Proteins: key players in bacterial cell cycle and drug resistance processes Macheboeuf, Pauline; Contreras-Martel, Carlos; Job, Viviana FEMS Microbiology Reviews, Vol. 30, Issue 5 https://doi.org/10.1111/j.1574-6976.2006.00024.x	journal	September 2006
Analysis of the Mechanism of Action of Potent Antibacterial Hetero-tri-organometallic Compounds: A Structurally New Class of Antibiotics Wenzel, Michaela; Patra, Malay; Senges, Christoph Helmut Rudi ACS Chemical Biology, Vol. 8, Issue 7 https://doi.org/10.1021/cb4000844	journal	April 2013
Kinship and Diversification of Bacterial Penicillin-Binding Proteins and β-Lactamases Massova, Irina; Mobashery, Shahriar Antimicrobial Agents and Chemotherapy, Vol. 42, Issue 1 https://doi.org/10.1128/AAC.42.1.1	journal	January 1998

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Title: Antibacterial Properties of Metallocenyl-7-ADCA Derivatives and Structure in Complex with CTX-M β-Lactamase

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