title: Synthesis, screening and computational investigation of pentacycloundecane-peptoids as potent CSA-HIV PR inhibitors.
abstract: Herein, we present the first pentacycloundecane (PCU) diol peptoid derived HIV protease inhibitors with IC(50) values ranging from 6.5 to 0.075 μM. 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.
authors.affiliation: School of Health Sciences, University of KwaZulu Natal, Durban 4001, South Africa.
authors.forename: Maya M
authors.initials: MM
authors.lastname: Makatini
authors.forename: Katja
authors.initials: K
authors.lastname: Petzold
authors.forename: Per I
authors.initials: PI
authors.lastname: Arvidsson
authors.forename: Bahareh
authors.initials: B
authors.lastname: Honarparvar
authors.forename: Thavendran
authors.initials: T
authors.lastname: Govender
authors.forename: Glenn E M
authors.initials: GE
authors.lastname: Maguire
authors.forename: Raveen
authors.initials: R
authors.lastname: Parboosing
authors.forename: Yasien
authors.initials: Y
authors.lastname: Sayed
authors.forename: Mahmoud E S
authors.initials: ME
authors.lastname: Soliman
authors.forename: Hendrik G
authors.initials: HG
authors.lastname: Kruger
mesh_terms: D020134:Catalytic Domain; D016333:HIV Protease / Q000737:chemistry* / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D015497:HIV-1 / Q000737:chemistry* / Q000201:enzymology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D034444:Peptoids / Q000138:chemical synthesis / Q000737:chemistry*; D011083:Polycyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D011485:Protein Binding; D013019:South Africa; D013329:Structure-Activity Relationship
chemical_list: D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D034444:Peptoids; D011083:Polycyclic Compounds; D016333:HIV Protease