(L-2-hydroxy-3-mercaptopropionic-acid)oxytocin. Circular dichroism studies of conformation and interaction with neurophysin.

The role of the α-amino group of oxytocin in affecting the conformation of oxytocin and its binding to neurophysin was studied by a comparison of the circular dichroism and binding properties of oxytocin with those of (L-2-hydroxy-3-mercaptopropionic acid)oxytocin which contains a hydroxyl in place of the oxytocin amino group. The circular dichroism properties of (L-2-hydroxy-3-mercaptopropionic acid)oxytocin were very similar to those of deamino-oxytocin (in which the amino group of oxytocin is replaced by a hydrogen) but differed significantly from those of oxytocin, particularly under conditions in which the oxytocin α-amino group is protonated. The protonated oxytocin α-amino group is known to participate in a salt-bridge with a neurophysin carboxyl at neutral pH, but oxytocin appears to bind to neurophysin without salt-bridge formation below pH 2. Nonetheless, (L-2-hydroxy-3-mercaptopropionic acid)oxytocin, like deamino-oxytocin, was found not to bind to the hormone-binding site of neurophysin with measurable affinity at either neutral pH or low pH. The results indicate that, in the binding of oxytocin to neurophysin, the protonated oxytocin α-amino group plays a role more complex than that of carboxylate charge neutralization and suggest that this role involves an effect on oxytocin conformation. However, highly specific bonding interactions between the α-amino group and neurophysin, additional to those of salt-bridge formation, are not precluded.