Monoclonal-based ELISA for the identification of herbicidal cyclohexanedione analogues that inhibit graminaceous acetyl coenzyme-A carboxylase.
Cyclohexanediones are one of four known structural classes of herbicides that inhibit graminaceous acetyl coenzyme-A carboxylase (ACCase; EC 6.4.1.2). Five monoclonal antibodies were raised against cyclohexanediones conjugated to bovine serum albumin. Cross-reactivity studies using a homologous competitive indirect enzyme-linked immunosorbent assay (ciELISA) against 24 cyclohexanedione analogues revealed that two monoclonal antibodies (mAb A and mAb B) could segregate the analogues into active and inactive ACCase inhibitors on the basis of the analogue concentration required to inhibit 50% of antibody binding to the coating conjugate (IC(50)). Both mAb A and mAb B were also found to cross-react with various members of the indolizidinedione structural class of ACCase inhibitors in ciELISA, suggesting that both cyclohexanediones and indolizidinediones possess features recognized by monoclonal antibodies important for the inhibition of ACCase activity. In conclusion, pharmacophore-specific antibodies may be potentially valuable screening tools for the identification of new lead chemistries in a pesticide discovery program.
Webb
S R
SR
Dow AgroSciences Canada Inc., Saskatoon, Saskatchewan, Canada.
Hall
J C
JC
D000103:Acetyl-CoA Carboxylase / Q000037:antagonists & inhibitors*; D000818:Animals; D000911:Antibodies, Monoclonal; D002417:Cattle; D003429:Cross Reactions; D003512:Cyclohexanones / Q000032:analysis* / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006540:Herbicides / Q000032:analysis* / Q000494:pharmacology; D015394:Molecular Structure; D006109:Poaceae / Q000201:enzymology*; D012710:Serum Albumin, Bovine; D013329:Structure-Activity Relationship
D000911:Antibodies, Monoclonal; D003512:Cyclohexanones; D006540:Herbicides; D012710:Serum Albumin, Bovine; D000103:Acetyl-CoA Carboxylase