Amino dermorphin

Montecucchi PC, de Castiglione R, Piani S, Gozzini L, Erspamer V. Amino acid composition and sequence of dermorphin, a novel opiate-like peptide from the skin of Phyllomedusa sauvagei. Int J Peptide Protein Res 1981 17 275-283. 

The screening of a cDNA library prepared from the skin of Ph. sauvagei established the amino acid sequence of several dermorphin precursors. The... 

Subsequently, two additional peptides with even higher affinity for the delta opiate receptor were isolated from the skin of Ph. bicolor [12], Like dermorphin, these peptides contain D-alanine as the second amino acid. They have been termed D-Ala-deltorphin-I and D-Ala-deltorphin-II. 

All the natural deltorphins, like the mu agonist dermorphins, contain the N-terminal sequence Tyr-D-Xaa-Phe, where the aromatic residues of Tyrl and Phe3 are of L configuration and the D-Xaa in the second position of the molecule is a D amino acid (D-Ala or D-Met or D-Leu). The D-enantiomer is encoded, however, by the codon for the L isomer in the precursor cDNA [8,13,15]. Thus, L-Xaa2 must be converted to D-Xaa2 by an unusual posttranslational reaction that presumably takes place in the precursor itself. 

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... 

Amino acid substitutions have been examined in every position of dermorphin (see Ref 663 for a review). An alanine scan of the peptide indicated that substitutions in positions 4, 6, and 7 are well tolerated, whereas substitution particularly in positions 1 or 2, but also in positions 3 or 5, results in large decreases in potency in the GPI (877). A o-amino acid in position 2 is important for activity, and the L-Ala peptide is virtually inactive (<0.1% the potency of dermorphin). Tetrapeptide analogs containing D-methionine sulfoxide in position 2 are also potent p-selective agonists (878). 

Kinetically controlled peptide synthesis synthesis ot bioactive peptides in organic solvent (dermorphin, enkephalin) amino acid oligomerization [22] di- and tripeptide synthesis with peptidomimetic leaving group [23-27]... 

The synthetic potential of papain in low water systems has been explored with acyl donors bearing the carbamoylmethyl (Cam) leaving group. Dipeptide synthesis proceeded in >80% yield, and yields up to 60% were obtain for the synthesis of bioactive peptides like dermorphin-(l-4) (Boc-Tyr-D-Ala-Phe-Gly-NH2). Papain is also used as a versatile protease in polymer chemistry for the synthesis of amino acid oligomers and cooligomers of a-hydroxy acids and amino acids [22]. 

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