Crystal structure and solution conformation of S,S′‐bis(Boc‐Cys‐Ala‐OMe): Intramolecular antiparallel β‐sheet conformation of an acyclic cystine peptide

Abstract

The conformation of the acyclic biscystine peptide S,S′-bis(Boc-Cys-Ala-OMe) has been studied in the solid state by x-ray diffraction, and in solution by¹H- and¹³C-nmr, ir, and CD methods. The peptide molecule has a twofold rotation symmetry and adopts an intramolecular antiparallel β-sheet structure in the solid state. The two antiparallel extended strands are stabilized by two hydrogen bonds between the Boc CO and Ala NH groups [N ⃛O 2.964 (3) Å, O ⃛HN 2.11 (3) Å, and NH ⃛O angle 162 (3)°]. The disulfide bridge has a right-handed conformation with the torsion angle C^βSSC^β = 95.8 (2)°. In solution the presence of a twofold rotation symmetry in the molecule is evident from the¹H- and¹³C-nmr spectra. ¹H-nmr studies, using solvent and temperature dependencies of NH chemical shifts, paramagnetic radical induced line broadening, and rate of deuterium-hydrogen exchange effects on NH resonances, suggest that Ala NH is solvent shielded and intramolecularly hydrogen bonded in CDCl₃ and in (CD₃)₂SO. Nuclear Overhauser effects observed between Cys C^αH and Ala NH protons and ir studies provide evidence of the occurrence of antiparallel β-sheet structure in these solvents. The CD spectra of the peptide in organic solvents are characteristic of those observed for cystine peptides that have been shown to adopt antiparallel β-sheet structures.