1357569-35-7Relevant academic research and scientific papers
Synthesis and NMR elucidation of pentacycloundecane-derived hydroxy acid peptides as potential anti-HIV-1 agents
Karpoormath, Rajshekhar,Albericio, Fernando,Govender, Thavendran,Maguire, Glenn E. M.,Kruger, Hendrik G.
, p. 1461 - 1471 (2013/10/22)
The synthesis and NMR elucidation of eight novel peptides incorporating the pentacycloundecane (PCU)-derived hydroxy acid are reported. The PCU cage amino acids were synthesized as racemates and the incorporation of the PCU-derived hydroxy acid with natural (S)-amino acids produced inseparable diastereomeric peptides. A series of overlapping signals from the cage and that of the peptide side chain was observed in the 1H- and 13C-NMR spectra, complicating the elucidation thereof. Two-dimensional NMR techniques proved to be a very useful tool in overcoming these difficulties. These compounds are potential HIV protease inhibitors.
Pentacycloundecane derived hydroxy acid peptides: A new class of irreversible non-scissile ether bridged type isoster as potential HIV-1 wild type C-SA protease inhibitors
Karpoormath, Rajshekhar,Sayed, Yasien,Govender, Patrick,Govender, Thavendran,Kruger, Hendrik G.,Soliman, Mahmoud E.S.,Maguire, Glenn E.M.
experimental part, p. 19 - 29 (2012/03/26)
Novel peptides incorporating the PCU derived hydroxy acid (5-hydroxy-4-oxahexacyclo[5.4.1.02,6.03,10.0 5,9.08,11]dodecane) were synthesized and their activity against the resistance-prone wild type C-South African (C-SA) HIV-protease is reported. The attachment of peptides and peptoids to the PCU derived hydroxy acid resulted in a series of structurally diverse promising HIV-1 protease inhibitors. Amongst the nine novel compounds, 16, 17, 20 and 23 gave IC 50 values ranging from 0.6 to 5.0 μM against the wild type C-SA HIV-1 protease enzyme. Docking studies and molecular dynamic (MD) simulations have been carried out in order to understand the binding mode of the PCU moiety at the active site of the HIV protease enzyme. A conserved hydrogen bonding pattern between the PCU derived hydroxy ether and the active site residues, ASP25/ASP25′, was observed in all active compounds.
