Abstract
Aim: The pharmacotherapy of inflammatory bowel disease is difficult and currently available treatments bring mostly poor and unsatisfactory results. 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. Conclusion: 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.
Financial & competing interests disclosure
This work was supported by the grants from the National Science Centre (#UMO-2013/11/B/NZ7/01301) and the Medical University of Lodz (#503/1-156-04/503-01 to J Fichna and #502-03/1-156-02/502-14-140 to M Salaga). M Salaga is supported by the Polpharma Scientific Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript
Ethical conduct of research
The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.