Hemorphin-4

Hemorphin-4 is an endogenous opioid peptide of the hemorphin family which possesses antinociceptive properties and is derived from the β-chain of hemoglobin in the bloodstream. It contains a tetrapeptide core with the amino acid sequence Tyr-Pro-Trp-Thr. Hemorphin-4 serves as a opioid receptor ligand that has affinities for the μ-, δ-, and κ-opioid receptors in the same range as the structurally related β-casomorphins, although affinity to the κ-opioid receptor is markedly higher in comparison. It acts as an agonist at these sites. It presents high affinity for other receptors such as angiotensin IV, bombesin subtype 3 (hBRS-3), and the corticotropin releasing factor (CRF). Even though it exhibits lower binding affinity for opioid receptors relative to traditional opioid peptides such as endorphins and enkephalins; it may still influence opioid receptor systems due to its high tissue concentration.

== Therapeutic potentials == Hemorphin-4 also has inhibitory effects on angiotensin-converting enzyme (ACE), and as a result, may play a role in the regulation of blood pressure. Notably, inhibition of ACE also reduces enkephalin catabolism. Upon modifications with adamantane and cyclohexane, the Hemorphin-4 analog inhibits insulin-regulated aminopeptidase (IRAP) compared to other angiotensin IV inhibitors, making it a suitable candidate for pain, anxiety, and depression therapies. In binding to the μ-opioid receptor, it has significant seizure-suppressing and pain-relieving properties and reduces involuntary bladder contractions in a similar manner to classic opioids.