4. Metal-free artificial diels-alderases

Two approaches have been used to generate artificial metal ion-free DAases: the use of catalytic antibodies or in silico enzyme design. As previously mentioned, the catalytic properties of enzymes for a given reaction are due to the stabilization of the ET of that reaction, which leads to a decrease in its activation energy. It was shown that antibodies selected against an ET or a mime of this ET possessed catalytic activity equivalent to that of enzymes. This marked the beginning of the era of catalytic antibodies and hence of artificial DAases. Thus, using the mammalian immune system, several groups succeeded in generating specific antibodies to catalyze the DA reaction. With the same objective, other groups have opted for in silico (or de novo) enzyme design, which has made remarkable progress in recent years thanks to the development of molecular modeling tools, enabling increasingly...