Development and evaluation of an immunological approach for the identification of novel acetyl coenzyme-A carboxylase inhibitors: assay optimization and pilot screen results.
Cyclohexanediones, aryloxyphenoxypropionates, indolizidinediones, and triazinediones are four known structural classes of herbicides that inhibit acetyl coenzyme-A carboxylase (ACCase; EC 6.4.1.2). An immunological study to determine the potential of ACCase inhibitor-specific monoclonal antibodies as screening tools to identify novel lead chemistry was undertaken. Using two cyclohexanedione-specific monoclonal antibodies (mAb A and mAb B; Webb, S. R.; Hall, J. C. J. Agric. Food Chem. 2000, 48, 1210-1218) and three different cyclohexanedione hapten coating conjugates, competitive indirect enzyme-linked immunosorbent assays (ciELISA) were developed. Cross-reactivity of the monoclonal antibodies with four structural classes of ACCase inhibitors revealed that the ciELISA using mAb A and a modified cyclohexanedione hapten coating conjugate detected analogues from all four known classes of ACCase inhibitors. A pilot screen using this ciELISA format identified two novel ACCase inhibitors, demonstrating the potential for antibodies as rapid and cost-effective screening tools for identifying novel lead chemistry in pesticide discovery programs.
Webb
S R
SR
Dow AgroSciences Canada Inc., 241-111 Research Drive, Saskatoon, Saskatchewan, Canada.
Hall
J C
JC
D000103:Acetyl-CoA Carboxylase / Q000037:antagonists & inhibitors*; D003512:Cyclohexanones / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000032:analysis* / Q000737:chemistry / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006540:Herbicides / Q000032:analysis* / Q000737:chemistry / Q000494:pharmacology; D007212:Indolizines / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology; D011422:Propionates / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014227:Triazines / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology
D003512:Cyclohexanones; D004791:Enzyme Inhibitors; D006540:Herbicides; D007212:Indolizines; D011422:Propionates; D014227:Triazines; D000103:Acetyl-CoA Carboxylase