title: Design, synthesis, and functional evaluation of CO-releasing molecules triggered by Penicillin G amidase as a model protease.
abstract: Protease-triggered CO-releasing molecules (CORMs) were developed. The viability of the approach was demonstrated through the synthesis of compounds consisting of an η(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.
authors.affiliation: Department für Chemie, Universität zu Köln, Greinstrasse 4, 50939 Köln (Germany).|Department of Organic Chemistry, Nizhni Novgorod State University, Gagarina av. 23, 603950 Nizhni Novgorod (Russia).
authors.forename: Nikolay S
authors.initials: NS
authors.lastname: Sitnikov
authors.affiliation: Medizinische Klinik, Universitätsmedizin Mannheim, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim (Germany).
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Li
authors.affiliation: Medizinische Klinik, Universitätsmedizin Mannheim, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim (Germany).
authors.forename: Danfeng
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Medizinische Klinik, Universitätsmedizin Mannheim, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim (Germany).
authors.forename: Benito
authors.initials: B
authors.lastname: Yard
authors.affiliation: Department für Chemie, Universität zu Köln, Greinstrasse 4, 50939 Köln (Germany). schmalz@uni-koeln.de.
authors.forename: Hans-Günther
authors.initials: HG
authors.lastname: Schmalz
mesh_terms: D000466:Alkadienes / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D002248:Carbon Monoxide / Q000378:metabolism*; D058085:Iron Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D015394:Molecular Structure; D010399:Penicillin Amidase / Q000737:chemistry / Q000378:metabolism*; D010400:Penicillin G / Q000378:metabolism*
chemical_list: D000466:Alkadienes; D058085:Iron Compounds; D002248:Carbon Monoxide; D010399:Penicillin Amidase; D010400:Penicillin G
keywords: carbon monoxide; carbonyl complexes; enzyme catalysis; iron; organometallic compounds