Premium
Inside Cover: Novel Insights into Structure–Activity Relationships of N‐Terminally Modified PACE4 Inhibitors (ChemMedChem 3/2016)
Author(s) -
Kwiatkowska Anna,
Couture Frédéric,
Levesque Christine,
Ly Kévin,
Beauchemin Sophie,
Desjardins Roxane,
Neugebauer Witold,
Dory Yves L.,
Day Robert
Publication year - 2016
Publication title -
chemmedchem
Language(s) - English
Resource type - Reports
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201600031
Subject(s) - lipid anchored protein , chemistry , in vivo , pegylation , peptide , amino acid residue , lncap , residue (chemistry) , pharmacology , stereochemistry , biochemistry , prostate cancer , apoptosis , peptide sequence , cancer , medicine , autophagy , biology , microbiology and biotechnology , polyethylene glycol , gene
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 a d ‐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. on page 289 in Issue 3, 2016 (DOI: 10.1002/cmdc.201500532).