| 摘要 |
<p>DNA polymerase β isolated from a member of the parasite family Trypanosomatidae, the species Trypanosoma brucei, has been determined to be the primary drug target for the trypanocidal agent berenil (diminazene aceturate), being four orders of magnitude more sensitive to the drug than is either human DNA polymerase β or α. DNA polymerases of the α family isolated from T. brucei, also effective targets of berenil, are two orders of magnitude more sensitive than either of the human enzymes. The discovery of the differential sensitivity of the DNA polymerases from T. brucei to a trypanocidal agent has permitted the development of methods for systematically identifying and using therapeutic agents effective in treating a patient suffering from an infection by a member of this family of parasites. The methods include testing the sensitivity of DNA polymerase α and DNA polymerase β from a member of the family Trypanosomatidae to a candidate trypanocidal agent, comparing the determined sensitivity of the DNA polymerases to the candidate agent, and testing the DNA polymerase having greater sensitivity against decreasing levels of the candidate agent. In this way a minimal effective dosage of the agent can be determined.</p> |
