MOLECULAR CONFORMATIONAL-ANALYSES OF DEHYDROALANINE ANALOGS

The conformational preferences of dehydroalanine (Delta Ala) were examined through ab initio calculations. The geometries of the minimum energy conformations for N-formyldehydro alanilamide and N-acetyl-N'-methylamide of dehydroalanine were determined by gradient optimization at the HF/6-31G* level, and correlation corrections were examined with MP2 single-point energy calculations. Furthermore, HF/3-21G ab initio geometry optimizations were performed on nine conformations of the model tripeptide N-acetyl-N'-methylamide of didehydroalanine. The results indicate that the C-5 is the lowest energy conformation at all levels of theory. However, the relative energy of the helix conformation decreases when the number of Delta Ala residues in the peptide chain increases. On the other hand, significant variations of the geometry upon conformational change were observed for the three compounds investigated. These results permit to extract important conformationally dependent geometry trends. The results of this study were compared to x-ray diffraction data on single crystals of dehydroalanine-containing peptides. (C) 1995 John Wiley & Sons, Inc.