Structure-based design and synthesis of HIV-1 protease inhibitors employing beta-D-mannopyranoside scaffolds.
A preliminary account on the structure-based design, synthesis and evaluation of peptidomimetic inhibitors of HIV-1 protease containing beta-D-mannopyranoside scaffolds is given. The compounds prepared had IC(50) values in the micromolar range. The results provide a platform for the development of more potent carbohydrate-based inhibitors of HIV-1 and other aspartic proteases.
Murphy
Paul V
PV
Chemistry Department, Centre for Synthesis and Chemical Biology, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland. paul.v.murphey@ucd.ie
O'Brien
Julie L
JL
Gorey-Feret
Lorraine J
LJ
Smith
Amos B
AB
D016282:Aspartic Acid Endopeptidases / Q000737:chemistry; D001665:Binding Sites; D015195:Drug Design; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D020128:Inhibitory Concentration 50; D008358:Mannose / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D008968:Molecular Conformation; D013329:Structure-Activity Relationship
D017320:HIV Protease Inhibitors; D016282:Aspartic Acid Endopeptidases; D008358:Mannose