Figure - available from: Scientific Reports
This content is subject to copyright. Terms and conditions apply.
![The chemical structures of the glycopeptide antibiotics and a PG-repeat unit. (a) Chemical structure of [¹⁹F]oritavancin with the biphenyl moiety highlighted in grey. (b) Chemical structure of chloroeremomycin with the 4-epi-vancosamine highlighted in grey. (c) Chemical structure of vancomycin with the first amino acid residue, N-methylleucine (grey circle). The cleavage of the N-methylleucine from [¹⁹F]oritavancin, chloroeremomycin, and vancomycin by Edman degradation results in desleucyl-[¹⁹F]oritavancin, desleucyl-chloroeremomycin, and desleucyl-vancomycin, respectively. (d) Chemical structure of the peptide portion of the PG-repeat unit in S. aureus with amino acid sequence acyl-l-Lys(Gly5)-d-Ala-d-Ala. A pentaglycine is attached to the ɛ-nitrogen of the l-Lys. The primary-binding site of the glycopeptide antibiotics binds to the d-Ala-d-Ala of the PG-repeat unit (grey oval). The PG disaccharide N-acetylglucosamine-N-acetylmuramic acid does not participate in the binding and thus was removed from the glycopeptide–PG complex.](publication/360271659/figure/fig1/AS:1150752521240582@1651372189604/The-chemical-structures-of-the-glycopeptide-antibiotics-and-a-PG-repeat-unit-a.png)
The chemical structures of the glycopeptide antibiotics and a PG-repeat unit. (a) Chemical structure of [¹⁹F]oritavancin with the biphenyl moiety highlighted in grey. (b) Chemical structure of chloroeremomycin with the 4-epi-vancosamine highlighted in grey. (c) Chemical structure of vancomycin with the first amino acid residue, N-methylleucine (grey circle). The cleavage of the N-methylleucine from [¹⁹F]oritavancin, chloroeremomycin, and vancomycin by Edman degradation results in desleucyl-[¹⁹F]oritavancin, desleucyl-chloroeremomycin, and desleucyl-vancomycin, respectively. (d) Chemical structure of the peptide portion of the PG-repeat unit in S. aureus with amino acid sequence acyl-l-Lys(Gly5)-d-Ala-d-Ala. A pentaglycine is attached to the ɛ-nitrogen of the l-Lys. The primary-binding site of the glycopeptide antibiotics binds to the d-Ala-d-Ala of the PG-repeat unit (grey oval). The PG disaccharide N-acetylglucosamine-N-acetylmuramic acid does not participate in the binding and thus was removed from the glycopeptide–PG complex.
Source publication
Oritavancin is a semisynthetic glycopeptide antibiotic used to treat severe infections by multidrug-resistant Gram-positive pathogens. Oritavancin is known to be a thousand times more potent than vancomycin against Gram-positive bacteria due to the additional interactions with bacterial peptidoglycan (PG) facilitated by a secondary-binding site. Th...
Citations
... Therefore, for instance, when vancomycin is added to S. aureus during growth, Park's nucleotide, a cytoplasmic PG-precursor, accumulates [91]. Vancomycin binding to lipid II is an efficient way to suppress both PG and wall teichoic acid biosynthesis in S. aureus [89], since C55 is present in a surprisingly low number of copies per bacterium [92] and is a shared transporter needed in these processes [93]. ...
This narrative review paper provides an up-to-date overview of the potential of novel synthetic and semisynthetic compounds as antibacterials that target virulence traits in resistant strains. The review focused on research conducted in the last five years and investigated a range of compounds including azoles, indoles, thiophenes, glycopeptides, pleuromutilin derivatives, lactone derivatives, and chalcones. The emergence and spread of antibiotic-resistant bacterial strains is a growing public health concern, and new approaches are urgently needed to combat this threat. One promising approach is to target virulence factors, which are essential for bacterial survival and path-ogenesis, but not for bacterial growth. By targeting virulence factors, it may be possible to reduce the severity of bacterial infections without promoting the development of resistance. We discuss the mechanisms of action of the various compounds investigated and their potential as antibacterials. The review highlights the potential of targeting virulence factors as a promising strategy to combat antibiotic resistance and suggests that further research is needed to identify new compounds and optimize their efficacy. The findings of this review suggest that novel synthetic and semisynthetic compounds that target virulence factors have great potential as antibacterials in the fight against antibiotic resistance.
The natural glycopeptide antibiotic teicoplanin is used for the treatment of serious Gram-positive related bacterial infections and can be administered intravenously, intramuscularly, topically (ocular infections), or orally. It has also been considered for targeting viral infection by SARS-CoV-2. The hydrodynamic properties of teicoplanin A2 (M1 = 1880 g/mol) were examined in phosphate chloride buffer (pH 6.8, I = 0.10 M) using sedimentation velocity and sedimentation equilibrium in the analytical ultracentrifuge together with capillary (rolling ball) viscometry. In the concentration range, 0–10 mg/mL teicoplanin A2 was found to self-associate plateauing > 1 mg/mL to give a molar mass of (35,400 ± 1000) g/mol corresponding to ~ (19 ± 1) mers, with a sedimentation coefficient s20, w = ~ 4.65 S. The intrinsic viscosity [η\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\eta$$\end{document}] was found to be (3.2 ± 0.1) mL/g: both this, the value for s20,w and the hydrodynamic radius from dynamic light scattering are consistent with a globular macromolecular assembly, with a swelling ratio through dynamic hydration processes of ~ 2.
The semi-synthetic glycan antibiotic teicoplanin is used for the treatment of serious Gram-positive related bacterial infections and can be administered intravenously, intramuscularly, topically (ocular infections), or orally. It has also been considered for targeting viral infection by SARS-CoV-2. The hydrodynamic properties of teicoplanin A2 (monomer molar mass ~ 1880 g/mol) were examined in phosphate chloride buffer (pH 6.8, I = 0.10 M) using sedimentation velocity and sedimentation equilibrium in the analytical ultracentrifuge together with capillary (rolling ball) viscometry. In the concentration range, 0-10 mg/mL teicoplanin A2 was found to self-associate plateauing > 1 mg/mL to give a molar mass of (35400 ± 1000) g/mol corresponding to ~ (19 ± 1) mers, with a sedimentation coefficient s20,w = ~ 4.65 S. The intrinsic viscosity [h] was found to be (3.2 ± 0.1) mL/g: both this, the value for s20,w and the hydrodynamic radius from dynamic light scattering is consistent with a globular macromolecular assembly, with a swelling ratio through dynamic hydration processes of ~2.
