[Capillary electrophoresis for monitoring stability of pharmaceutical proteins].
Like chemical drugs, pharmaceutical proteins have to be of strictly controlled purity to become biopharmaceuticals. Detection, identification and characterization of impurities and compounds present in purified biopharmaceuticals are of central interest. Simultaneous development of structural biology, biotechnologies and of highly resolutive analytical tools, allow significant progress in this field to be achieved. Thus, capillary electrophoresis can be advantageously used for monitoring protein stability. As illustrated by the examples of potential enzymes for detoxification of organophosphates, prophylaxis and treatment of poisoning by pesticides and nerve agents or for skin decontamination, the present feature article shows that this new methodological approach allows: to determine purity and homogeneity of proteins;to analyze their resistance to denaturing conditions such as heat or high electric fields;to detect the presence of unwanted hidden protein-bound ligands capable of altering functional conformation and stability of enzymes, and moreover susceptible to be released and to induce side effects, such as immunologic response; and to establish the role of parameters controlling the "good compromise" between conformational stability and plasticity for allowing optimal functional efficiency of enzymes. Finally, capillary electrophoresis has proved to be a pertinent tool to validate the conformity of purified enzymes to a status of biopharmaceutical.
Rochu
D
D
Centre de Recherches du Service de Santé des Armées, Département de Toxicologie, Unité d'Enzymologie, 24, avenue des Maquis du Grésivaudan, BP 87, F 38702 La Tronche Cedex. danielrochu@crssa.net
Masson
P
P
D000110:Acetylcholinesterase / Q000737:chemistry; D004355:Drug Stability; D019075:Electrophoresis, Capillary; D004798:Enzymes / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*
D004798:Enzymes; D004364:Pharmaceutical Preparations; D011506:Proteins; D000110:Acetylcholinesterase
Application de l'électrophorèse capillaire au contrôle de la stabilité des protéines pharmaceutiques.