Thus in either analogs, the two carboxylic functions of terminal Asp residue are stabilized by potential H-bonding with the side chain residues of Arg⁵ and Lys⁹. The substrate (I) displayed a conformational preference with an inverse-β-turn structure consisting of a somewhat unusual 11-membered intra-molecular H-bonding. This leads to a more exposed P1-P1’ peptide bond (Arg⁵-CO-NH-Leu⁶) and a significant lack of stabilization of this bond. In contrast, the inhibitor, β-Cha analog (II) exhibited in its average conformation the presence of a β-turn structure containing a 10-membered intra-molecular H-bond. As a consequence, the amide carbonyl group between Arg⁵-β Cha⁶(P1-P1’) became strongly polarized by the electrostatic interactions with the side chain of Lys⁴ situated in close proximity. In these circumstances, the corresponding acyl-enzyme intermediate becomes stabilized by intramolecular H-bonding and resistant to the hydrolytic cleavage. Other important structural differences include the observation that, P1’Leu residue side chain in (I) is directed towards the interior of the molecule in contrast to (II) where P1’βCha residue side chain is projected to the exterior of the molecule, causing a more steric hindrance. Based on the NMR data in conjunction with molecular modelling studies, using Monte-Carlo conformational search, plausible three-dimensional structures were postulated for (I) and (II). The implications of such conformations in relationship to their interactions with PCs are discussed.