title: Anti-inflammatory effect of novel analogs of natural enkephalinase inhibitors in a mouse model of experimental colitis.
abstract: The pharmacotherapy of inflammatory bowel disease is difficult and currently available treatments bring mostly poor and unsatisfactory results.
  
  
  
  The purpose of this work was the synthesis of opiorphin, sialorphin, spinorphin and a series of their analogs and the in vitro characterization of their effect on degradation of enkephalin by neutral endopeptidase and aminopeptidase N. Consequently, we investigated in vivo the anti-inflammatory effect of the most active inhibitors selected in the in vitro studies (Pal-KKQRFSR & Pal-KKQHNPR). Putative inhibitor - enzyme (neutral endopeptidase or aminopeptidase N) complexes are also presented and their binding interfaces are identified.
  
  
  
  Our results suggest that Pal-KKQHNPR has the potential to become a valuable template for anti-inflammatory therapeutics for the treatment of GI tract inflammation.
authors.affiliation: Faculty of Chemistry, University of Gdansk, Gdansk, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Kamysz
authors.affiliation: Faculty of Medicine, Medical University of Lodz, Lodz, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Sałaga
authors.affiliation: Faculty of Chemistry, University of Gdansk, Gdansk, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Sobocińska
authors.affiliation: Faculty of Chemistry, University of Gdansk, Gdansk, Poland.
authors.forename: Artur
authors.initials: A
authors.lastname: Giełdoń
authors.affiliation: Faculty of Medicine, Medical University of Lodz, Lodz, Poland.
authors.forename: Jakub
authors.initials: J
authors.lastname: Fichna
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003092:Colitis / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D015260:Neprilysin / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001688:Biological Products; D004791:Enzyme Inhibitors; D015260:Neprilysin
keywords: aminopeptidase N; colitis; molecular modeling; neutral endopeptidase; opiorphin; peptide synthesis; sialorphin; spinorphin