Inside Cover: Novel Insights into Structure–Activity Relationships of N‐Terminally Modified PACE4 Inhibitors (ChemMedChem 3/2016). Issue 3 (2nd February 2016)

• Record Type: Journal Article
• Authors: Kwiatkowska, Anna; Couture, Frédéric; Levesque, Christine; Ly, Kévin; Beauchemin, Sophie; Desjardins, Roxane; Neugebauer, Witold; Dory, Yves L.; Day, Robert
• Is Part Of: ChemMedChem. Volume 11:Issue 3(2016)
• Page Start: 247
• Page End: 247
• Publication Date: 2016-02-02
• Subjects: enzyme inhibitors -- PACE4 -- proprotein convertases -- prostate cancer -- structure–activity relationships; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201600031
• Languages: English
• ISSNs: 1860-7179

Abstract

Abstract : The inside cover picture shows a challenging ′journey′ from a lead PACE4 inhibitor (ML peptide) into a drug‐like compound for in vivo administration. Different routes have been taken to improve properties of the ML inhibitor, including N‐terminal PEGylation and lipidation. The effect of these modifications on activity, stability, toxicity, and cell penetration of the resulting analogs was evaluated. Our results show that the best inhibitor was obtained not by N‐terminal extensions but the protection of both ends with ad ‐amino acid residue and an arginine mimetic, indicating that simple solutions are sometimes more effective. These modifications significantly improved activity and stability profile and led to a compound ready for in vivo studies as a potential anti‐prostate cancer agent. More information can be found in the Full Paper by Yves L. Dory, Robert Day et al. onpage 289 in Issue 3, 2016 (DOI:10.1002/cmdc.201500532 ).