{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Garsi JB"],"funding":["Natural Sciences and Engineering Research Council of Canada"],"pagination":["949-954"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9190036"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["13(6)"],"pubmed_abstract":["On the basis of the knowledge that the proline-rich hot spot <b>PPP</b>RPP region of P(151)PSNPPPRPP(160), an oligopeptide derived from the cytosolic portion of p22<sup>phox</sup> (p22), binds to the single functional bis-SH3 domain of the regulatory protein p47<sup>phox</sup> (p47), we designed a mimetic of the tripeptide <b>PPP</b> based on NMR and X-ray crystallographic data for the p22(151-161) peptide PPSN<b>PPP</b>RPPA with a peptide construct. Incorporation of the synthetic pseudo-triproline mimetic Pro-Pro-Cyp in a molecule derived from molecular modeling studies led to only a 7-fold diminution in activity in a surface plasmon resonance assay relative to the same molecule containing the natural Pro-Pro-Pro tripeptide. The alternative sequence corresponding to a Pro-Cyp-Pro insertion was inactive. This is a first example of the use of a triproline mimetic to interfere with the formation of the p47-p22 complex, which is critical for the activation of NOX, leading to the production of reactive oxygen species as superoxide anions."],"journal":["ACS medicinal chemistry letters"],"pubmed_title":["Targeting NOX2 via p47/phox-p22/phox Inhibition with Novel Triproline Mimetics."],"pmcid":["PMC9190036"],"funding_grant_id":["IRCPJ 531309 - 17"],"pubmed_authors":["Szlavik Z","Lancelot N","Cullia G","Fordos E","Sipos Z","Vuillard LM","Balazs B","Brown D","Fejes I","Markacz P","Komjati B","Cukier C","Garsi JB","Raimbaud E","Hanessian S","Sipos M","Berger S","Haberkorn L"],"additional_accession":[]},"is_claimable":false,"name":"Targeting NOX2 via p47/phox-p22/phox Inhibition with Novel Triproline Mimetics.","description":"On the basis of the knowledge that the proline-rich hot spot <b>PPP</b>RPP region of P(151)PSNPPPRPP(160), an oligopeptide derived from the cytosolic portion of p22<sup>phox</sup> (p22), binds to the single functional bis-SH3 domain of the regulatory protein p47<sup>phox</sup> (p47), we designed a mimetic of the tripeptide <b>PPP</b> based on NMR and X-ray crystallographic data for the p22(151-161) peptide PPSN<b>PPP</b>RPPA with a peptide construct. Incorporation of the synthetic pseudo-triproline mimetic Pro-Pro-Cyp in a molecule derived from molecular modeling studies led to only a 7-fold diminution in activity in a surface plasmon resonance assay relative to the same molecule containing the natural Pro-Pro-Pro tripeptide. The alternative sequence corresponding to a Pro-Cyp-Pro insertion was inactive. This is a first example of the use of a triproline mimetic to interfere with the formation of the p47-p22 complex, which is critical for the activation of NOX, leading to the production of reactive oxygen species as superoxide anions.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Jun","modification":"2025-04-27T02:21:11.418Z","creation":"2025-04-06T18:32:36.752Z"},"accession":"S-EPMC9190036","cross_references":{"pubmed":["35707140"],"doi":["10.1021/acsmedchemlett.2c00094"]}}