Bicyclic peptides: Solid state conformation of cyclo(Glu‐Leu‐Pro‐Gly‐Lys‐Leu‐Pro‐Gly)cyclo(1γ‐5ϵ)Gly

The solid state conformational analysis of the ionophoric homodetic bicyclic cyclo(Glu‐Leu‐Pro‐Gly‐Lys‐Leu‐Pro‐Gly)cyclo(1γ‐5ϵ)Gly (BCP3) has been carried out by x‐ray diffraction. It crystallizes with 4.5 molecules of water per peptide molecule in the monoclinic system, space group P21, with a = 11.425 Å, b = 16.616 Å, c = 13.931 Å, β = 109.24°, and Z = 2. The structure has been determined by direct methods and refined to an R factor of 0.061 for 2448 observed reflections. The structure characterized by all trans peptide bonds is stabilized by three intramolecular hydrogen bonds: a type II β‐turn, a mixed type I‐type III β‐turn, and a pseudo γ‐turn, which involves the side chain CO and the main‐chain NH groups of the Glu1 residue. The resulting globular molecule presents a rather hydrophilic surface with most of the CO groups available to hydration of the solvent molecules, which are linked through hydrogen bonds of the NH … O or OH … O types in a complicated H‐bonding scheme. The conformation observed in the solid state is rather different from the conformation proposed in solution for both the free and the Ca2+‐complexed BCP3 molecule. Copyright © 1990 John Wiley & Sons, Inc.