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Prospects for novel inhibitors of peptidoglycan transglycosylases.

Galley NF, O'Reilly AM, Roper DI - Bioorg. Chem. (2014)

Bottom Line: The lack of novel antimicrobial drugs under development coupled with the increasing occurrence of resistance to existing antibiotics by community and hospital acquired infections is of grave concern.The targeting of biosynthesis of the peptidoglycan component of the bacterial cell wall has proven to be clinically valuable but relatively little therapeutic development has been directed towards the transglycosylase step of this process.Advances towards the isolation of new antimicrobials that target transglycosylase activity will rely on the development of the enzymological tools required to identify and characterise novel inhibitors of these enzymes.

View Article: PubMed Central - PubMed

Affiliation: School of Life Sciences, University of Warwick, Coventry CV4 7AL, UK.

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The structure of Moenomycin A, the only known potent inhibitor for bacterial transglycosylases. The region highlighted in blue is the minimal inhibitory pharmacophore, which is often used as a scaffold for the design of new potential inhibitors (discussed in Section 3.1).
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f0015: The structure of Moenomycin A, the only known potent inhibitor for bacterial transglycosylases. The region highlighted in blue is the minimal inhibitory pharmacophore, which is often used as a scaffold for the design of new potential inhibitors (discussed in Section 3.1).

Mentions: The moenomycins are a family of glycolipid antibiotics naturally produced as a complex of related compounds by Streptomyces ghananensis with moenomycin A representing the major component with antimicrobial activity [9,58]. Moenomycin consists of a pentasaccharide of units B, C, D, E and F with a chromophore (unit A) and a C25 lipid chain connected to the F saccharide via a phosphoglycerate linker (see Fig. 3). The C25 chain is required for antimicrobial action and in essence the moenomycin structure resembles that of the lipid IV product formed within the transglycosylase active site [59].


Prospects for novel inhibitors of peptidoglycan transglycosylases.

Galley NF, O'Reilly AM, Roper DI - Bioorg. Chem. (2014)

The structure of Moenomycin A, the only known potent inhibitor for bacterial transglycosylases. The region highlighted in blue is the minimal inhibitory pharmacophore, which is often used as a scaffold for the design of new potential inhibitors (discussed in Section 3.1).
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4126109&req=5

f0015: The structure of Moenomycin A, the only known potent inhibitor for bacterial transglycosylases. The region highlighted in blue is the minimal inhibitory pharmacophore, which is often used as a scaffold for the design of new potential inhibitors (discussed in Section 3.1).
Mentions: The moenomycins are a family of glycolipid antibiotics naturally produced as a complex of related compounds by Streptomyces ghananensis with moenomycin A representing the major component with antimicrobial activity [9,58]. Moenomycin consists of a pentasaccharide of units B, C, D, E and F with a chromophore (unit A) and a C25 lipid chain connected to the F saccharide via a phosphoglycerate linker (see Fig. 3). The C25 chain is required for antimicrobial action and in essence the moenomycin structure resembles that of the lipid IV product formed within the transglycosylase active site [59].

Bottom Line: The lack of novel antimicrobial drugs under development coupled with the increasing occurrence of resistance to existing antibiotics by community and hospital acquired infections is of grave concern.The targeting of biosynthesis of the peptidoglycan component of the bacterial cell wall has proven to be clinically valuable but relatively little therapeutic development has been directed towards the transglycosylase step of this process.Advances towards the isolation of new antimicrobials that target transglycosylase activity will rely on the development of the enzymological tools required to identify and characterise novel inhibitors of these enzymes.

View Article: PubMed Central - PubMed

Affiliation: School of Life Sciences, University of Warwick, Coventry CV4 7AL, UK.

Show MeSH
Related in: MedlinePlus