Functional Mimicry of the Active Site of Carboxypeptidase A by a Molecular Imprinting Strategy:  Cooperativity of an Amidinium and a Copper Ion in a Transition-State Imprinted Cavity Giving Rise to High Catalytic Activity

• Published in: Journal of the American Chemical Society 2004-06, Vol.126 (24), p.7452-7453
• Main Authors: Liu, Jun-qiu, Wulff, Günter
• Format: Article
• Language: English
• Subjects: Amides - chemistry; Applied sciences; Binding Sites - physiology; Carboxypeptidases A - chemistry; Carboxypeptidases A - physiology; Catalysis; Copper - chemistry; Exact sciences and technology; Kinetics; Models, Chemical; Molecular Mimicry; Molecular Structure; Organic polymers; Oxidation-Reduction; Physicochemistry of polymers; Properties and characterization; Special properties (catalyst, reagent or carrier)
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja048372l

A model for the natural enzyme carboxypeptidase A was prepared by molecular imprinting in synthetic polymers. An unusually high activity and efficiency for carbonate hydrolysis could be obtained by imprinting with a stable transition-state analogue template and introducing an amidinium group and a Cu2+ ion-binding site in a defined orientation to each other into the active site. With substrates having a very similar structure to the template, extraordinarily high enhancements of rates of 110 000-fold were obtained of catalyzed to uncatalyzed reaction k cat/k uncat . The efficiency k cat/K m of the molecularly imprinted catalysts compared to that of the nonimprinted control polymers containing the same functional groups was 790-fold higher, a clear indication of a very efficient imprinting procedure.