Identification of a novel opioid peptide (Tyr-Val-Pro-Phe-Pro) derived from human αS1 casein (αS1-casomorphin, and αS1-casomorphin amide)

A new casomorphin pentapeptide (α_S1-casomorphin) has been isolated from the sequence of human α_S1-casein [α_S1-casein-(158–162)], with the sequence Tyr-Val-Pro-Phe-Pro. This peptide was found to bind with high affinity to all three subtypes of the κ-opioid receptor (κ₁–κ₃). When amidated at the C-terminus, α_S1-casomorphin amide binds to the Δ- and κ₃-opioid sites. Both α_S1-casomorphin and its amide inhibit in a dose-dependent and reversible manner the proliferation of T47D human breast cancer cells. This anti-proliferative activity was greater for α_S1-casomorphin, which was the most potent opioid in inhibiting T47D cell proliferation. In T47D breast cancer cells, other casomorphins have been found to bind to somatostatin receptors in addition to opioid sites. In contrast, α_S1-casomorphin and its amide do not interact with somatostatin receptors in our system.