Cystine peptides. The anti parallel β-sheet conformation of two synthetic cyclic bi(cystine peptides)

Abstract

Conformational studies on two synthetic cyclic bis(cystine peptides) have been carried out. The NMR data support a C₂-symmetric structure possessing four intramolecular hydrogen bonds in CDCl₃ and (CD₃)₂SO solutions. The involvement of the X-NH and NHMe groups in formation of transannular hydrogen bonds is inferred from the temperature and solvent dependences of NH chemical shifts, hydrogen-deuterium-exchange rates, and radical-induced line-broadening experiments. IR studies over a wide concentration range also favor hydrogen-bonded structures. Unusually low C^αH chemical shifts for Cys¹ and Cys³ residues, high J_HNC^αH values (≥9 Hz), and the observation of nuclear Overhauser effects between C_i^αH and N_i+1H protons in 1 provide compelling evidence for an antiparallel α-sheet conformation for the 22-membered cyclic bis(cystine peptides).