Conformational studies on beta-amino acid-containing peptides. I.

Modified amino acids (such as beta-amino acids) are becoming increasingly popular research tools in the development of orally active and metabolically stable peptidomimetics. We present conformational energy calculations using molecular mechanics (MM2) on two model compounds containing beta-amino acids. The low-energy models are characterized by a lack of intramolecular hydrogen-bonding interactions, qualitatively consistent with the results of the IR studies. The structures obtained from the limited amount of x-ray crystal data on compounds with beta-amino acid incorporated lie within 3 kcal/mol of the global minimum obtained from the present calculations. Preliminary stereochemical guidelines for the incorporation of beta-amino acid residues have been proposed.