Molecular design of polymer catalysts for the esterolysis of a marked amino acid ester substrate Z-L-Leu-PNP (PNP=p-nitrophenol) was performed. Either a transition-state analogue of Z-Leu-PP (phenyl 1-benzyloxycarbonly-3-methylpentylphosphonate) or a ground-state analogue of Z-L-Leu-AA (ethyl N-benzyloxycarbonyl-L-leucine-anthranilate) was used as a template molecule. In the esterolyses of amino acid esters in 10 vol% dimethyl sulfoxide (DMSO)-Tris buffer (pH 7.15) at 293 similar to 308 K, several water-soluble or insoluble polymer catalysts containing a L-histidine catalytic site, which were synthesized by the radical polymerization with acrylamide derivatives, incorporated the marked substrate into their reaction cavities effectively. An ammonium-chain containing water-soluble polymer catalyst exhibited a remarkable acceleration of the present reaction. The free energy of activation (23.9 kcal/mol at 303 K) of the uncatalyzed reaction decreased 7.0 kcal/mol.