INSERTION OF THE METHYLENE-OXY SURROGATE OF THE AMIDE BOND INTO BOC-VAL-LEU-OH - X-RAY CRYSTAL-STRUCTURE, SOLUTION CONFORMATION AND MOLECULAR MODELING STUDY

The conformational features associated with the introduction of the me thylene-oxy surrogate of the amide bond were explored by studying the crystal and solution conformation of the related model peptides Boc-Va l-Leu-OH (1) and Boc-Val-psi(CH2O)-Leu-OH (2). Two independent molecul ar conformations were found for 1 in the crystal state whereas one was found for its congener 2. In compound 2 the dihedral angle defined by C(alpha)-CH2-O-C(alpha) (omega') adopts a value of -165.7(3)degrees. close to the situation encountered in the classical amide bond. 2D NOE NMR studies suggest that the preferred backbone conformation of 2 in [H-2(6)]DMSO correlates with the crystal structure whereas the preferr ed backbone conformation of 1 in [H-2(6)]DMSO showed a departure from its crystalline conformation. Molecular mechanics computations demonst rate the effect of the short C(sp3)-O(Sp3) bond in compound 2 in dicta ting the preferred dihedral angle values adopted by omega' and phi(Leu ).