Enzyme Models—From Catalysis to Prodrugs
Enzymes are highly specific biological catalysts that accelerate the rate of chemical reac-tions within the cell. Our knowledge of how enzymes work remains incomplete. Computationalmethodologies such as molecular mechanics (MM) and quantum mechanical (QM) methods play animportant role in elucidating the detailed mechanisms of enzymatic reactions where experimentalresearch measurements are not possible. Theories invoked by a variety of scientists indicate thatenzymes work as structural scaffolds that serve to bring together and orient the reactants so that thereaction can proceed with minimum energy. Enzyme models can be utilized for mimicking enzymecatalysis and the development of novel prodrugs. Prodrugs are used to enhance the pharmacokineticsof drugs; classical prodrug approaches focus on alternating the physicochemical properties, whilechemical modern approaches are based on the knowledge gained from the chemistry of enzymemodels and correlations between experimental and calculated rate values of intramolecular processes(enzyme models). A large number of prodrugs have been designed and developed to improve theeffectiveness and pharmacokinetics of commonly used drugs, such as anti-Parkinson (dopamine), an-tiviral (acyclovir), antimalarial (atovaquone), anticancer (azanucleosides), antifibrinolytic (tranexamicacid), antihyperlipidemia (statins), vasoconstrictors (phenylephrine), antihypertension (atenolol),antibacterial agents (amoxicillin, cephalexin, and cefuroxime axetil), paracetamol, and guaifenesin.This article describes the works done on enzyme models and the computational methods used tounderstand enzyme catalysis and to help in the development of efficient prodrugs.
enzymes , computational methods , catalytic models , intramolecularity , proton transferreactions , prodrug approach