Bicyclic peptides. V. Conformation and ion binding of an undeca and a dodeca bicyclic peptide

Abstract

The ion binding characteristics of two bicyclic peptides, cyclo(Lys-Pro-Gly-Pro-Gly-Glu-Pro-Gly-Pro-Gly)-cyclo(1ε → 6γ) Gly (BCP7) and cyclo(Lys-Pro-Gly-Pro-Gly-Glu-Pro-Gly-Pro-Gly)-cyclo(1ε → 6γ) Gly-Gly (BCP8) in a lipophilic solvent, acetonitrile, have been studied using CD and nmr spectroscopy. The data indicate that both BCP7 and BCP8 preferentially bind divalent ions. The nmr data showed that the conformation of both peptides in the free state was an average of many rapidly interconverting conformational states. The nmr titration data for Ca⁺² ions with BCP7 and BCP8 indicated that both of these bicyclic peptides bind to calcium ions forming stable 1 : 1 and possibly 1 : 2 Ca⁺²:BCP-type complexes. The conformation of the Ca⁺²:BCP7 and Ca⁺²:BCP8 complexes were similar, with each containing two type I β-turns, one cis X-Pro bond and three trans X-Pro bonds. In the 1 : 1 complex, the Ca⁺² ion coordinates to four carbonyl oxygens from the face opposite the bridgehead peptide as well as to two carbonyl oxygens from the interior of the cavity.