Cystine Peptides. The Antiparallel \beta -Sheet Conformation of Two Synthetic Cyclic Bis( cystine peptides)

Conformational studies on two synthetic cyclic bis(cystine peptides) have been carried out. The NMR data support a $C_2$-symmetric structure possessing four intramolecular hydrogen bonds in $CDCI_3$ and $(CD_3)_2$SO 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 $C^\alpha H$ chemical shifts for $Cys^1$ and $Cys^3$ residues, high $^JHNC^\alpha H$ values (9H z), and the observation of nuclear Overhauser effects between $C_i^\alpha H$ and $N_i_+_1H$ protons in 1 provide compelling evidence for an antiparallel \beta -sheet conformation for the 22-membered cyclic bis(cystine peptides)