Synthesis and conformational studies of peptidomimetics containing a carbocyclic 1,3-diacid

A rigid carbocyclic scaffold comprising of an all-cis 4,5-dihydroxy-1,3-cyc lopentanedicarboxylic acid is developed. Attachment of peptide strands to t he carboxylic groups of this novel template led to the peptidomimetics 2 an d 3. Conformational analysis by circular dichroism and NMR studies revealed that these molecules adopt a unique folded structure in nonpolar solvent i nvolving intramolecular hydrogen bonding between PheNH of one strand and Le uC=O (in 2) or GlyC=O (in 3) of the other strand. This structure is very di fferent from the structures observed earlier in their sugar counterparts (1 ). The paper describes in detail the synthesis and structural studies of co mpounds 2 and 3. (C) 2001 Elsevier Science Ltd. All rights reserved.