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Søhoel H, Liljefors T, Ley SV, Oliver SF, Antonello A, Smith
MD, Olsen CE, Isaacs JT, Christensen SB.
Total synthesis of two novel
subpicomolar sarco/endoplasmatic reticulum Ca2+-ATPase
inhibitors designed by an analysis of the binding site of
thapsigargin.
J Med Chem.
2005 Nov 3;48(22):7005-11
Department of Medicinal Chemistry, The Danish University of
Pharmaceutical Sciences, Universitetsparken 2, DK-2100
Copenhagen , Denmark.
Analysis of molecular interaction fields based on the
published crystal structure of thapsigargin bound to the
sarco/endoplasmatic reticulum Ca(2+)-ATPase and analysis of the
volume and shape of the ligand binding site and of the
SERCA-thapsigargin interactions have enabled design of two new
compounds inhibiting SERCA in the subpicomolar range. The two
inhibitors were synthesized using (S)-carvone as starting
material and found to be 3 and 10 times more potent than
thapsigargin.
PMID: 16250659 |
