A new strategy in transition-state analog design is demonstrated to elicit catalytic antibodies. The strategy is based on substrate-assisted antibody catalysis and utilizes analogs designed to mimic the transition-state for intramolecular catalysis and thereby favor antibodies that can recruit catalytic groups from substrate. The hydrolysis of the benzoyl ester of cocaine provides an illustration. The benzoyl ester of cocaine is distant from the protonated nitrogen in the stable chair conformer but proximate in the strained boat form. An antibody stabilizing the boat form and approximating ester and amine could catalyze ester hydrolysis. To mimic the transition-state for the intramolecular catalysis, we synthesized a cocaine analog that replaces this ester with a methylenephenylphosphinate bridge to the tropane nitrogen. This bridged analog elicited 85 cocaine esterases out of 450 anti-analog antibodies-a performance markedly superior to that of a simple phosphonate ester-based analog with an identical tether. The correspondence of the analog to a "high energy" conformer eliminated product inhibition. For certain polyfunctional targets, substrate assistance can be an effective strategy for eliciting catalytic antibodies.