A long sought-after goal of bioorganic chemists is a fundamental understanding of the chemical and structural bases of enzymatic catalysis. A final goal of such insight would be the ability to construct de novo catalysts that could effectively catalyze the desired reactions. This proposal is aimed at constructing small molecule mimics of protein disulfide isomerase (PDI), an enzyme responsible for catalyzing the formation of disulfide bonds in vivo. The design of the mimics is such that they will be able to form a mimic-substrate complex through transient Schiff base formation, and thus better catalysts because the effective concentration of the mimic will be enhanced in the complex. The designed mimics should provide an excellent system for understanding the nature of the actual PDI-substrate complex. If successful, this methodology could be applied to a wide variety of biological reactions and would have potential medical and biotechnological applications.
