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.