Design, synthesis, and functional evaluation of CO‐releasing molecules triggered by penicillin G amidase as a model protease

• Verfasst von: Sitnikov, Nikolay S. [VerfasserIn]
• Verfasst von: Li, Yingchun [VerfasserIn]
• Verfasst von: Zhang, Danfeng [VerfasserIn]
• Verfasst von: Yard, Benito A. [VerfasserIn]
• Titel: Design, synthesis, and functional evaluation of CO‐releasing molecules triggered by penicillin G amidase as a model protease
• Verf.angabe: Nikolay S. Sitnikov, Yingchun Li, Danfeng Zhang, Benito Yard, and Hans-Günther Schmalz
• E-Jahr: 2015
• Jahr: 2 June 2015
• Umfang: 5 S.
• Fussnoten: Gesehen am 22.03.2018
• Titel Quelle: Enthalten in: Angewandte Chemie. International edition
• Ort Quelle: Weinheim : Wiley-VCH, 1998
• Jahr Quelle: 2015
• Band/Heft Quelle: 54(2015), 42, Seite 12314-12318
• ISSN Quelle: 1521-3773
• DOI: doi:10.1002/anie.201502445
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: carbon monoxide
• Sach-SW: carbonyl complexes
• Sach-SW: enzyme catalysis
• Sach-SW: iron
• Sach-SW: organometallic compounds
• K10plus-PPN: 1571324062

Abstract

Abstract Protease?triggered CO?releasing molecules (CORMs) were developed. The viability of the approach was demonstrated through the synthesis of compounds consisting of an ?4?oxydiene?Fe(CO)3 moiety connected to a penicillin?G amidase (PGA)?cleavable unit through a self?immolative linker. The rate of PGA?induced hydrolysis was investigated by HPLC analysis and the subsequent CO release was quantitatively assessed through headspace gas chromatography. In an in?vitro assay with human endothelial cells, typical biological effects of CO, that is, inhibition of the inflammatory response and the induction of heme oxygenase?1 expression, were observed only upon co?administration of the CORM and PGA. This work forms a promising basis for the future development of protease?specific CORMs for potential medicinal applications.