Synthesis of polyamine derivatives for the preparation of affinity chromatography columns for the search of new Trypanosoma cruzi targets.
The most potent trypanocidal compound of a series of symmetrically substituted 1,4-bis(3-aminopropylpiperazines) which displayed an IC50 value of 5 microM on Trypanosoma cruzi trypomastigotes, was inactive on trypanothione reductase. Two derivatives 6 and 12 of this compound, one symmetrical and one dissymmetrical, were synthesized via a reductive amination reaction, to prepare affinity chromatography columns, which allowed us to isolate three parasitic proteins. Among these, the major ligand 6- and 12-binding protein having an apparent molecular weight of 52 kDa has been identified as the thiol-disulfide oxido-reductase Tc52, previously characterized in Trypanosoma cruzi.
Davioud-Charvet
E
E
Institut de Biologie et Institut Pasteur de Lille - UMR CNRS 8525 - Faculté de Pharmacie - Université de Lille II, France.
Berecibar
A
A
Girault
S
S
Landry
V
V
Drobecq
H
H
Sergheraert
C
C
D000818:Animals; D015153:Blotting, Western; D002846:Chromatography, Affinity; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D011073:Polyamines / Q000138:chemical synthesis*; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects
D010879:Piperazines; D011073:Polyamines; D014344:Trypanocidal Agents