Theoretical Prediction of Substituent Effects on the Intrinsic Folding Properties of β-Peptides

Abstract

A systematic conformational analysis on blocked β-amino acids as constituents of β-peptides by ab initio MO theory reveals that the conformer pool of β-peptide monomers is essentially determined by the conformation of simple submonomer fragments. The influence of single and multiple substitutions at the C(α) and C(β) backbone atoms on the intrinsic folding properties of the monomers was estimated both in the single-molecule approximation and in a polar solvent continuum, applying a quantum-chemical SCRF model. Substitution at C(β) has a higher impact on the β-amino acid conformation than a substitution at C(α). It can be shown that the conformations of important periodic secondary structures in β-peptides belong to the conformer pool of the monomers, even for those secondary-structure elements where H-bond formation appears only in longer sequences. Rules for design of special secondary-structure types by selection of an actual substituent pattern in the β-amino acid constituents have been derived within the monomer approach.