Sortase A Inhibitors: Recent Advances and Future Perspectives.
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.
Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, Sezione di Chimica e Tecnologie Farmaceutiche, Università degli Studi di Palermo , Via Archirafi 32, 90123 Palermo, Italy.|IEMEST, Istituto Euromediterraneo di Scienza e Tecnologia , Via Emerico Amari, 123, 90139 Palermo, Italy.
Stella
S
Cascioferro
Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, Sezione di Chimica e Tecnologie Farmaceutiche, Università degli Studi di Palermo , Via Archirafi 32, 90123 Palermo, Italy.
Demetrio
D
Raffa
Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, Sezione di Chimica e Tecnologie Farmaceutiche, Università degli Studi di Palermo , Via Archirafi 32, 90123 Palermo, Italy.
Benedetta
B
Maggio
Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, Sezione di Chimica e Tecnologie Farmaceutiche, Università degli Studi di Palermo , Via Archirafi 32, 90123 Palermo, Italy.
Maria Valeria
MV
Raimondi
Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, Sezione di Chimica e Tecnologie Farmaceutiche, Università degli Studi di Palermo , Via Archirafi 32, 90123 Palermo, Italy.
Domenico
D
Schillaci
Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, Sezione di Chimica e Tecnologie Farmaceutiche, Università degli Studi di Palermo , Via Archirafi 32, 90123 Palermo, Italy.
Giuseppe
G
Daidone
D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology; D019881:Aminoacyltransferases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D001422:Bacterial Adhesion / Q000187:drug effects; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D001565:Benzoates / Q000737:chemistry / Q000494:pharmacology; D002243:Carbolines / Q000737:chemistry / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D009570:Nitriles / Q000737:chemistry / Q000494:pharmacology; D011487:Protein Conformation; D012236:Rhodanine / Q000031:analogs & derivatives / Q000494:pharmacology; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000201:enzymology* / Q000472:pathogenicity; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology; D013871:Thiones / Q000737:chemistry / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001565:Benzoates; D002243:Carbolines; D004791:Enzyme Inhibitors; D009570:Nitriles; D054852:Small Molecule Libraries; D013844:Thiazoles; D013871:Thiones; D012236:Rhodanine; D019881:Aminoacyltransferases; C120542:sortase A; D003546:Cysteine Endopeptidases; D000218:Adamantane