Highly active antibacterial ferrocenoylated or ruthenocenoylated Arg-Trp peptides can be discovered by an<scp>l</scp>-to-<scp>d</scp>substitution scan

Albada, Bauke; Prochnow, Pascal; Bobersky, Sandra; Bandow, Julia E.; Metzler‐Nolte, Nils

doi:10.1039/c4sc01822b

Cited by 47 publications

(45 citation statements)

References 36 publications

(22 reference statements)

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“…We hope that the proposed method will find wide application in biochemical studies of antimicrobial and anticancer peptides, which commonly contain tryptophan residues 21. 22…”

Section: Methodsmentioning

confidence: 99%

Selective Ruthenium Labeling of the Tryptophan Residue in the Bee Venom Peptide Melittin

Perekalin

Novikov

Pavlov

et al. 2015

Chemistry A European J

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Melittin is a membrane-active peptide from bee venom with promising antimicrobial and anticancer activity. Herein we report on a simple and selective method for labeling of the tryptophan residue in melittin by the organometallic fragment [(C5 H5 )Ru](+) in aqueous solution and in air. Ruthenium coordination does not disturb the secondary structure of the peptide (as verified by 2D NMR spectroscopy), but changes the pattern of its intermolecular interactions resulting in an 11-fold decrease of hemolytic activity. The high stability of the organometallic conjugate allowed the establishment of the biodistribution of the labeled melittin in mice by inductively coupled plasma MS analysis of ruthenium.

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“…We hope that the proposed method will find wide application in biochemical studies of antimicrobial and anticancer peptides, which commonly contain tryptophan residues 21. 22…”

Section: Methodsmentioning

confidence: 99%

Selective Ruthenium Labeling of the Tryptophan Residue in the Bee Venom Peptide Melittin

Perekalin

Novikov

Pavlov

et al. 2015

Chemistry A European J

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“…21 The activities against methicillin resistant Staphylococcus aureus (MRSA) of the organometallic derivatives of such peptides are now identical to, 22 or even better than, vancomycin without inducing substantial hemolysis and displaying high toxicity in vitro. 23 These last two effects are usually problematic for lipidated AMPs. Their effect on planktonic growth and biofilm formation of Escherichia coli was also determined, showing promising results for the former, but limited results for the latter.…”

Section: Introductionmentioning

confidence: 99%

Synergistic activity of a short lipidated antimicrobial peptide (lipoAMP) and colistin or tobramycin against Pseudomonas aeruginosa from cystic fibrosis patients

et al. 2016

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“…19–22 Antibacterial mechanisms of organometallic compounds are diversified, and in some cases they overcome antibiotic resistance in pathogenic bacteria. 20, 21 The idea of metallocene to β-lactam antibiotic conjugation is not new and fits into the more general concept of organometallic drug derivatization often used in bioorganometallic chemistry. 15 The first ferrocenyl (Fc) derivatives of 6-aminopenicillinic acid (6-APA) and 7-aminocephalosporanic acid (7-ACA) were reported in 1970s.…”

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confidence: 99%

“…This contact highlights a unique feature of Ru in interacting with –OH, 41, 42 particularly in the context of protein-ligand interactions. 21 …”

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confidence: 99%

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

et al. 2017

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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.

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Highly active antibacterial ferrocenoylated or ruthenocenoylated Arg-Trp peptides can be discovered by anl-to-dsubstitution scan

Abstract: By taking a systematic approach several short organometallic AMP conjugates were discovered which have very low hemolytic activity but virtually the same antimicrobial activity against MRSA as that of vancomycin.

Cited by 47 publications

References 36 publications

Selective Ruthenium Labeling of the Tryptophan Residue in the Bee Venom Peptide Melittin

Selective Ruthenium Labeling of the Tryptophan Residue in the Bee Venom Peptide Melittin

Synergistic activity of a short lipidated antimicrobial peptide (lipoAMP) and colistin or tobramycin against Pseudomonas aeruginosa from cystic fibrosis patients

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

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