beta-loop, gamma-loop, and helical peptide conformations in cyclopeptides containing a steroidal pseudo-amino acid

The steroidal pseudo-amino acids 3 alpha-amino-5 beta-cholan-24-oic acid (2a), 12 alpha-acetoxy-3 alpha-amino-5 beta-cholan-24-oic acid (2b), and 7 alpha,12 alpha-diacetoxy-3 alpha-amino-5 beta-cholan-24-oic acid (2c) are used as rigid spacers in the backbone of the cyclic peptides cyclo(-2a-Phe-Phe-)(2) (1a), cyclo(-2b-Phe-Phe-)(2) (1b), and cyclo(-2c-Phe-Phe-)(2) (1c). A homogeneous beta I-loop conformation is found in the peptide chains of la and Ib, while Ic exists as a mixture of a-helical and gamma-loop conformations. The structure and homogeneity of the conformations are established by several NMR techniques and are supported by molecular-dynamics calculations. The peptide conformations depend on the distance and attraction of the two large and lipophilic steroidal parts of the cyclic molecules.