A Mimic of Both a Torsionally-Distosrted Peptide Ground State and the Transition State for Peptide Bond Hydrolysis: Synthesis of a Spiro[4,4]nonyi Derivative

摘要

Because of their potential utility for catalyzing novel reactions with high substrate specificity, antibody catalysts have attracted much attention. To date, however, no general method for eliciting antibody peptidases has been developed (although some notable successes have been reported. Thus, we have been focusing on a new strategy: immunization with analogues that mimic not only the transition state for peptide bond hydrolysis but also a distorted peptide ground state. After incorporation into longer peptides, these derivatives may elicit antibodies that catalyze sequence-specific peptide bond hydrolysis both by destabilizing the bound peptide substrate and by stabilizing the transition state.