Catalytic antibodies entropy trap

Designing haptens in order to stimulate the production of catalytic antibodies depends on a variety of strategies based on transition state analogs, entropy traps and opportunistic chemistry. 

The influence of the hydrophobic effect on the aqueous pericychc reactions can be compared with the effect of catalytic antibodies. Antibodies have been found to catalyze Diels-Alder reactions, hetero-Diels-Alder reactions, and Claisen and oxy-Cope rearrangements. It is suggested that antibodies catalyze these reactions by acting as an entropy trap, primarily through binding and orienting the substrates in the cyclic conformations. 

Hilvert s group used the same hapten [26] with a different spacer to generate an antibody catalyst which has very different thermodynamic parameters. It has a high entropy of activation but an enthalpy lower than that of the wild-type enzyme (Table 1, Antibody 1F7, Appendix entry 13.2a) (Hilvert et al., 1988 Hilvert and Nared, 1988). Wilson has determined an X-ray crystal structure for the Fab fragment of this antibody in a binary complex with its TSA (Haynes et al., 1994) which shows that amino acid residues in the active site of the antibody catalyst faithfully complement the components of the conformationally ordered transition state analogue (Fig. 11) while a trapped water molecule is probably responsible for the adverse entropy of activation. Thus it appears that antibodies have emulated enzymes in finding contrasting solutions to the same catalytic problem. 

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