Dermorphins, amphibian skin

The first peptide family of amphibian opiates was discovered in 1981 and named dermorphins [2,3], Until the discovery of mammalian endomor-phins by Zadina et al. [4], these peptides represented the most potent and selective mu opiate receptor agonists identified in living organisms. Nine years later, deltorphins were discovered in the amphibian skin. These peptides are still the most potent and selective delta opiate agonists available today [5]. 

Based on their finding amphibian skin peptides, which were counterparts to other mammalian bioactive peptides, Erspamer and coworkers examined amphibian skin for opioid peptides (see Ref 663 for a review). This led first to the isolation and characterization of dermorphin (212, Fig. 7.41), which is a ja-se-lective peptide (see Table 7.13), from the skin of South American Phyllemedusinae hylid frogs in the early 1980s (664). Inspection of the sequence of one of the cloned cDNAs for the precursor of dermorphin suggested the existence of another heptapeptide with a similar iV-terminal sequence (665). This then led to the isolation of deltorphin (alsocalled dermenkephalin or deltorphin A, 213, Fig. 7.41), the first S-selective amphibian opioid peptide, from these frogs (666, 667). Synthesis confirmed that the amino acid in position 2 of deltorphin was o-methionine rather than L-methionine (666,668, 669). Two additional peptides [o-Ala ldeltorphin I (also referred to as deltorphin C, 214, Fig. 7.41) and [o-Ala ]deltorphin II (also referred to as deltorphin B, 25, Fig. 7.5) were subsequently discovered (106) which exhibited even greater 8-receptor affinity and exceptional selectivity... 

The opioid peptides stem from a large precursor molecule in which several copies of the enkephalins are present, the ratio between Met-enkephalin and Leu-enkephalin being 6 1 [39]. The same precursor, pro-opiocortin, also contains a modified form of the enkephalin sequence in which the N-terminal tyrosine is present as the sulfate ester [40]. This kind of post-translational change has been discussed in connection with gastrin, cholecystokinin and caerulein (p. 165). The last mentioned peptide prompts us to recall dermorphin (p. 186), an opioid peptide found in the skin of an amphibian. 

---