NORBORNYL DIPEPTIDE ANALOGS - MIMICS OF BOTH A TRANSITION-STATE AND ATORSIONALLY DISTORTED GROUND-STATE

The -amino-2-hydroxybicyclo[2.2.1]heptane-7-carboxylic acid derivative s 1-3 have been synthesized, the pivotal step being the use of an acyl nitrene-insertion reaction to introduce nitrogen functionality into t he corresponding hydroxy ester. The analogues each mimic a distorted p eptide ground state as well as the transition state for peptide bond h ydrolysis. To enhance the immune response and to provide further seque nce specificity, the analogues 1-3 have been coupled to at least one D -amino acid residue to yield the derivatives 21, 26, and 27, respectiv ely. Antibodies elicited against these derivatives may catalyze the hy drolysis of the corresponding peptides both by straining the substrate ground state and by stabilizing the transition state. (C) 1995 Academ ic Press, Inc.