Synthesis, screening and computational investigation of pentacycloundecane-peptoids as potent CSA-HIV PR inhibitors
2012 (English)In: European Journal of Medicinal Chemistry, ISSN 0223-5234, E-ISSN 1768-3254, Vol. 57, 459-467 p.Article in journal (Refereed) Published
Herein, we present the first pentacycloundecane (PCU) diol peptoid derived HIV protease inhibitors with IC50 values ranging from 6.5 to 0.075 mu M. Five derivatives were synthesized in an attempt to understand the structure activity relationship of this class of compounds for HIV protease inhibition. NMR spectroscopy (new Efficient Adiabatic Symmetrized Rotating Overhauser Effect Spectroscopy, EASY-ROESY) was employed to determine the predominant conformation of the active compound. In this study docking studies and MD simulations provided insight into the binding theme of this class of peptoid inhibitors to the CSA-HIV PR active site. Conserved and stable hydrogen bonding between the hydroxyl groups of the inhibitors and the active site Asp25/Asp25' residues were observed from the docking and along the MD trajectories.
Place, publisher, year, edition, pages
2012. Vol. 57, 459-467 p.
Transition state analogs, IC50, Pentacycloundecane diol-peptoid, CSA-HIV-1 wild type C-SA protease, EASY-ROESY, Molecular docking, MD simulations
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-193042DOI: 10.1016/j.ejmech.2012.06.019ISI: 000312621700047OAI: oai:DiVA.org:uu-193042DiVA: diva2:601158