1a.Objectives (from AD-416):
Establish mutually productive collaboration to discover and develop target-specific pesticides to control parasitic arthropods impacting animal and public health.
1b.Approach (from AD-416):
We will provide enzymatically active recombinant acetylcholinesterases from several economically important pests, beginning with rBmAChE1, the major acetylcholinesterase (AChE) of Rhipicephalus (Boophilus) microplus, and following with AChEs from other pest species, including sand flies, ticks, and biting flies. Cooperator will screen various ligands for specific binding to the AChEs that result in blocking the enzymatic activity. It is also possible that other binding sites may result in pesticidal activity without blocking enzymatic activity. Candidate control ligands will, in turn, be provided to KBUSLIRL scientists for in vivo and in vitro screening to test control efficacy against target pests.
The objective of the study is to identify and characterize biochemical differences between the cattle tick acetylcholinesterase proteins as a step toward elucidating their functions in vivo. An improved model of the enzyme structure and structural rearrangements associated with binding and catalysis has been developed and new inhibitors identified that have enhanced specificity for tick enzymes and predicted reduced toxicity for humans and cattle.