Abstract |
Here, we describe the most promising small synthetic organic compounds that act as potent Sortase A inhibitors and cater the potential to be developed as antivirulence drugs. Sortase A is a polypeptide of 206 amino acids, which catalyzes two sequential reactions: (i) thioesterification and (ii) transpeptidation. Sortase A is involved in the process of bacterial adhesion by anchoring LPXTG-containing proteins to lipid II. Sortase A inhibitors do not affect bacterial growth, but they restrain the virulence of pathogenic bacterial strains, thereby preventing infections caused by Staphylococcus aureus or other Gram-positive bacteria. The efficacy of the most promising inhibitors needs to be comprehensively evaluated in in vivo models of infection, in order to select compounds eligible for the treatment of bacterial infections in humans.
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Authors | Stella Cascioferro, Demetrio Raffa, Benedetta Maggio, Maria Valeria Raimondi, Domenico Schillaci, Giuseppe Daidone |
Journal | Journal of medicinal chemistry
(J Med Chem)
Vol. 58
Issue 23
Pg. 9108-23
(Dec 10 2015)
ISSN: 1520-4804 [Electronic] United States |
PMID | 26280844
(Publication Type: Journal Article)
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Chemical References |
- Anti-Bacterial Agents
- Bacterial Proteins
- Benzoates
- Carbolines
- Enzyme Inhibitors
- Nitriles
- Small Molecule Libraries
- Thiazoles
- Thiones
- Rhodanine
- Aminoacyltransferases
- sortase A
- Cysteine Endopeptidases
- Adamantane
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Topics |
- Adamantane
(analogs & derivatives, pharmacology)
- Aminoacyltransferases
(antagonists & inhibitors, chemistry, metabolism)
- Animals
- Anti-Bacterial Agents
(chemistry, pharmacology)
- Bacterial Adhesion
(drug effects)
- Bacterial Proteins
(antagonists & inhibitors, chemistry, metabolism)
- Benzoates
(chemistry, pharmacology)
- Carbolines
(chemistry, pharmacology)
- Cysteine Endopeptidases
(chemistry, metabolism)
- Enzyme Inhibitors
(chemistry, pharmacology)
- Humans
- Models, Molecular
- Nitriles
(chemistry, pharmacology)
- Protein Conformation
- Rhodanine
(analogs & derivatives, pharmacology)
- Small Molecule Libraries
(chemistry, pharmacology)
- Staphylococcal Infections
(drug therapy, microbiology)
- Staphylococcus aureus
(drug effects, enzymology, pathogenicity)
- Thiazoles
(chemistry, pharmacology)
- Thiones
(chemistry, pharmacology)
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