1H N.M.R. STUDY OF THE CONFORMATION OF [Glu 4] OXYTOCIN AND ITS LANTHANIDE COMPLEXES IN AQUEOUS SOLUTION

At 400 MHz the ¹H chemical shifts, peptide NH‐CαH coupling constants (J_Nα) and peptide hydrogen exchange rates of [Glu⁴] oxytocin in aqueous solution closely resemble those previously reported for oxytocin under comparable conditions, indicating that both the parent hormone and its analogue have similar conformations in this solvent. The hydrogen exchange data suggest a dynamic equilibrium between conformation(s) in which the peptide NH's of Asn⁵ Cys⁶ are internally hydrogen bonded and conformation(s) in which these hydrogens are bonded to the solvent. [Glu⁴]oxytocin forms 1:1 complexes with lanthanide metal ions. The diamagnetic La³⁺ complex exhibits values of J_Nα very similar to those of the metal free hormone analogue, suggesting that coordination of the metal is accompanied by minimal perturbation of the peptide backbone. Specific average proton‐metal distances estimated from Gd³⁺ induced paramagnetic relaxation effects indicate that the metal is probably coordinated to the Glu⁴ carboxyl group and the sidechain carbonyl of Asn⁵. Limiting shifts induced by binding of paramagnetic Yb³⁺ are also reported.