Deltorphins from frog skin

Current evidence indicates that analgesia mediated by agonist activation of 8-opioid receptors [44] produces less marked side-effects than analgesia mediated by p-opioid receptors [18]. Deltorphins which represent the potent family of opioid peptides originally isolated from frog skin [45] are the most selective 8-opioid receptor peptides. Thus, they have served as parent peptide in the synthesis of numerous 8 active peptide analogues. 

Another class of 5-selective peptides, isolated from extracts of frog skin, is the deltorphins. These compounds are based on the stmcture... 

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... 

Deltorphins are endogenous linear heptapeptides, isolated from skin extracts of frogs belonging to the genus Phyllomedusa, that have a higher affinity and selectivity for delta opioid-binding sites than any other natural compound known [36]. Two deltorphins with the sequence Tyr-Ala-Phe-Asp (or Glu)-Val-Val-Gly-NH2 have been identified and well characterized [36]. 

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