Probing of the cis-5-phenyl proline scaffold as a platform for the synthesis of mechanism-based inhibitors of the Staphylococcus aureus sortase SrtA isoform.
cis-5-Phenyl prolinates with electrophilic substituents at the fourth position of a pyrrolidine ring were synthesized by 1,3-dipolar cycloaddition of arylimino esters with divinyl sulfone and acrylonitrile. 4-Vinylsulfonyl 5-phenyl prolinates inhibit Staphylococcus aureus sortase SrtA irreversibly by modification of the enzyme Cys184 and could be used as hits for the development of antibacterials and antivirulence agents.
Kudryavtsev
Konstantin V
KV
Department of Chemistry, M.V. Lomonosov Moscow State University, 119991, Moscow, Russian Federation. kudr@org.chem.msu.ru
Bentley
Matthew L
ML
McCafferty
Dewey G
DG
D019881:Aminoacyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011392:Proline / Q000031:analogs & derivatives* / Q000737:chemistry; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000378:metabolism; D013211:Staphylococcus aureus / Q000201:enzymology*; D013450:Sulfones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
C541089:5-phenyl proline; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D020033:Protein Isoforms; D013450:Sulfones; C009873:divinyl sulfone; D011392:Proline; D019881:Aminoacyltransferases; C120542:sortase A; D003546:Cysteine Endopeptidases