Conjugates of Desmycosin with Fragments of Antimicrobial Peptide Oncocin: Synthesis, Antibacterial Activity, Interaction with Ribosome

Khairullina, Zimfira Z; Makarov, G. I.; Tereshchenkov, Andrey G.; Buev, Vitaly S.; Lukianov, Dmitrii A.; Polshakov, Vladimir I.; Tashlitsky, Vadim N.; Osterman, Ilya А.; Sumbatyan, N. V.

doi:10.1134/s0006297922090024

Cited by 3 publications

(3 citation statements)

References 100 publications

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“…Antibiotic activity was also evaluated against the following strains: E. coli JW5503 Δ tolC (KanS) ermC , modified with the plasmid pKH80 [ 59 ], providing resistance to erythromycin due to the expression of ErmC methyltransferase; E. coli SQ171 Δ tolC transformed with the pAM552 plasmid [ 60 ]; E. coli SQ171 Δ tolC modified with the pAM552 plasmid with A2059G substitution in the 23S rRNA; E. coli JW1052 Δ mdtH ; E. coli JW0912 Δ ompF ; and E. coli JW0368 Δ sbmA [ 57 ]. The procedure was performed as described previously in [ 33 ]. In short, Petri dishes filled with LB solid medium containing a selective antibiotic and 1.5% agar were covered with the tested strains.…”

Section: Methodsmentioning

confidence: 99%

“…In recent years, the search has continued for derivatives of both oncocin and bactenecins that are resistant to proteolytic degradation, have broader antibacterial activity, act against resistant bacterial strains, and possess other interesting and useful properties. These kinds of derivatives have been created either by replacing various amino acid residues with others contributing to the stability against proteolysis [ 30 , 31 , 32 ] or by combining peptides related to Bac7 with other antibiotics [ 33 ], antiviral drugs [ 34 ], or peptide nucleic acids (PNAs) [ 35 ] within the same molecule, or by conjugating two different AMPs [ 36 ], as well as on the basis of deep mutational scanning [ 37 ].…”

Section: Introductionmentioning

confidence: 99%

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Triphenylphosphonium Analogs of Short Peptide Related to Bactenecin 7 and Oncocin 112 as Antimicrobial Agents

Tereshchenkov,

Khairullina,

Volynkina

et al. 2024

Pharmaceutics

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Antimicrobial peptides (AMPs) have recently attracted attention as promising antibacterial agents capable of acting against resistant bacterial strains. In this work, an approach was applied, consisting of the conjugation of a peptide related to the sequences of bactenecin 7 (Bac7) and oncocin (Onc112) with the alkyl(triphenyl)phosphonium (alkyl-TPP) fragment in order to improve the properties of the AMP and introduce new ones, expand the spectrum of antimicrobial activity, and reduce the inhibitory effect on the eukaryotic translation process. Triphenylphosphonium (TPP) derivatives of a decapeptide RRIRPRPPYL were synthesized. It was comprehensively studied how the modification of the AMP affected the properties of the new compounds. It was shown that while the reduction in the Bac7 length to 10 a.a. residues dramatically decreased the affinity to bacterial ribosomes, the modification of the peptide with alkyl-TPP moieties led to an increase in the affinity. New analogs with structures that combined a decapeptide related to Bac7 and Onc112—Bac(1–10, R/Y)—and TPP attached to the C-terminal amino acid residue via alkylamide linkers, inhibited translation in vitro and were found to be more selective inhibitors of bacterial translation compared with eukaryotic translation than Onc112 and Bac7. The TPP analogs of the decapeptide related to Bac7 and Onc112 suppressed the growth of both Gram-negative bacteria, similar to Onc112 and Bac7, and Gram-positive ones, similar to alkyl-TPP derivatives, and also acted against some resistant laboratory strains. Bac(1–10, R/Y)-C2-TPP, containing a short alkylamide linker between the decapeptide and TPP, was transferred into the E. coli cells via the SbmA transporter protein. TPP derivatives of the decapeptide Bac(1–10, R/Y) containing either a decylamide or ethylamide linker caused B. subtilis membrane depolarization, similar to alkyl-TPP. The Bac(1–10, R/Y)-C2-TPP analog was proven to be non-toxic for mammalian cells using the MTT test.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Triphenylphosphonium Analogs of Short Peptide Related to Bactenecin 7 and Oncocin 112 as Antimicrobial Agents

Tereshchenkov,

Khairullina,

Volynkina

et al. 2024

Pharmaceutics

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show abstract

“…Antibiotic activity was also evaluated against the following strains: E. coli JW5503 ∆tolC (KanS) ermC, modified with the plasmid pKH80 [59], providing resistance to erythromycin due to the expression of ErmC methyltransferase; E. coli SQ171 ∆tolC transformed with the pAM552 plasmid [60]; E. coli SQ171 ∆tolC modified with the pAM552 plasmid with A2059G substitution in the 23S rRNA; E. coli JW1052 ∆mdtH; E. coli JW0912 ∆ompF; and E. coli JW0368 ∆sbmA [57]. The procedure was performed as described previously in [33]. In short, Petri dishes filled with LB solid medium containing a selective antibiotic and 1.5% agar were covered with the tested strains.…”

Section: Antibacterial Activity Of Substances On Agar Platesmentioning

confidence: 99%

Triphenylphosphonium Analogs of Short Peptide Related to Bactenecin 7 and Oncocin 112 as Antimicrobial Agents

Tereshchenkov,

Khairullina,

Volynkina

et al. 2023

Preprint

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Triphenylphosphonium (TPP) derivatives of a decapeptide related to sequences of bactenecin 7 (Bac7) and oncocin (Onc112) were synthesized and studied as potential antimicrobial compounds using various biochemical and microbiological assays. It was shown that while the reduction of the Bac7 length to 10 a.a. residues dramatically decreases the affinity to bacterial ribosomes, the modification of peptide with alkyl-TPP moieties leads to an increase in the affinity. New analogs which structure combines a decapeptide related to Bac7 and Onc112 — Bac(1-10, R/Y) — and TPP, attached to the C-terminal amino acid residue through alkylamide linkers, inhibit translation in vitro and are found to be more selective inhibitors of bacterial translation as compared with eukaryotic translation, than Onc112 and Bac7. Triphenylphosphonium analogs of a decapeptide related to Bac7 and Onc112 suppress the growth of both gram-negative bacteria, similar to Onc112 and Bac7, and gram-positive ones as alkyl-TPP derivatives, and also act against some resistant laboratory strains. Bac(1-10, R/Y)-C2-TPP, containing a short alkylamide linker between the decapeptide and TPP, is transferred into the E. coli cells via the SbmA transporter protein. TPP derivatives of the decapeptide Bac(1-10, R/Y) containing either decylamide or ethylamide linker cause B. subtilis membrane depolarization, similar to alkyl-TPP. The Bac(1-10, R/Y)-C2-TPP analog is proved to be non-toxic for mammalian cells by MTT-test.

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No country for old antibiotics! Antimicrobial peptides (AMPs) as next-generation treatment for skin and soft tissue infection

Răileanu

Borlan

Campu

et al. 2023

International Journal of Pharmaceutics

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Conjugates of Desmycosin with Fragments of Antimicrobial Peptide Oncocin: Synthesis, Antibacterial Activity, Interaction with Ribosome

Cited by 3 publications

References 100 publications

Triphenylphosphonium Analogs of Short Peptide Related to Bactenecin 7 and Oncocin 112 as Antimicrobial Agents

Triphenylphosphonium Analogs of Short Peptide Related to Bactenecin 7 and Oncocin 112 as Antimicrobial Agents

Triphenylphosphonium Analogs of Short Peptide Related to Bactenecin 7 and Oncocin 112 as Antimicrobial Agents

No country for old antibiotics! Antimicrobial peptides (AMPs) as next-generation treatment for skin and soft tissue infection

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