Characterization of a benzyl-phenoxy-ethanamine binding protein in Trypanosoma equiperdum and the possible relation between binding affinity and trypanocidal activity.
A new family of benzyl-phenoxy-ethanamine derivatives has been assayed for trypanocidal activity. Using tritiated morpholino-benzyl-phenoxy-ethanamine as a probe, it is shown that this ligand is able to bind specifically to a protein contained in extracts of Trypanosoma equiperdum. The binding is saturable and of high affinity (KD = 4 nM: Bmax = 200 fmol (mg protein)-1). The in vitro activities of the investigated compounds against this parasite correlate with their affinities to the putative binding site. Moreover, using an azido functionalized morpholino-benzyl-phenoxyethanamine as photoprobe a major M(r) = 40,000 protein was specifically revealed by sodium dodecyl sulphate polyacrylamide gel electrophoresis. This molecular weight corresponds with the previously observed value determined for the antioestrogen binding site protein of rat liver which has been shown to specifically bind antioestrogens of the triphenylethylene family and phenoxyethanamine derivatives.
Betbeder
D
D
Groupe de Chimie Organique Biologique, URA/CNRS 454/470, Université Paul Sabatier, Toulouse, France.
Perie
J J
JJ
Baltz
T
T
Poirot
M
M
Faye
J C
JC
D000345:Affinity Labels; D000818:Animals; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D004965:Estrogen Antagonists / Q000378:metabolism; D004983:Ethanolamines / Q000378:metabolism*; D007700:Kinetics; D015800:Protozoan Proteins / Q000737:chemistry / Q000378:metabolism*; D014344:Trypanocidal Agents / Q000378:metabolism / Q000494:pharmacology; D014345:Trypanosoma / Q000187:drug effects / Q000378:metabolism*
D000345:Affinity Labels; D002352:Carrier Proteins; D004965:Estrogen Antagonists; D004983:Ethanolamines; D015800:Protozoan Proteins; D014344:Trypanocidal Agents