Conformation of d‐Phe‐Cys‐Tyr‐d‐Trp‐Lys‐Thr‐Pen‐Thr‐NH₂ (CTP‐NH₂), a highly selective mu‐opioid antagonist peptide, by ¹H and ¹³C n.m.r.

The ¹ H and ¹³C n.m.r. spectral parameters of CTP‐NH₂ [d‐Phe‐Cys‐Tyr‐d‐Trp‐Lys‐Thr‐Pen‐Thr‐NH₂], a potent, highly selective μ‐opiate antagonist, were measured in aqueous solution and a possible conformation has been deduced from the spectral data. The data are consistent with a type II'β‐turn for the tetrapeptide sequence ‐Tyr³‐d‐Trp⁴‐Lys⁵‐Thr⁶‐. Solvent shielding of the Cys² amide proton, observed in variable temperature experiments, suggests an orientation of this amide proton toward the gem dimethyls of Pen⁷ with possible hydrogen bonding to the Thr⁶ carbonyl oxygen, and a dihedral angle of −110° for the disulfide bond. Partially relaxed Fourier transform ¹³C relaxation studies confirm a constrained cyclic system, with the Cα carbons in the “hinge” of the β‐turn having the shortest t₁ times. Segmental motion was observed for the side chain of Lys⁵.