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Melphalan potently substitutes the N‐terminal Tyr of D‐Ala 2 ‐Leu 5 ‐enkephalin methyl ester
Author(s) -
Szücs Mária,
Di Gleria Katalin,
Medzihradszky Kálmán
Publication year - 1985
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(85)80197-6
Subject(s) - terminal (telecommunication) , enkephalin , chemistry , stereochemistry , biochemistry , opioid , receptor , computer science , telecommunications
In search of an affinity label of the opioid receptor, the nitrogen mustard melphalan, Mel, was built into the peptide chain of D‐Ala 2 ‐Leu 5 ‐enkephalin (DALE) methyl ester in different positions. We report now that in contrast to the previous observations that an intact Tyr in position 1 is essential for opioid activity [(1980) Annu. Rev. Pharmacol. Toxicol. 20, 81‐110], substitution of Tyr by Mel did not result in a loss of the binding affinity. Mel 1 , Leu 5 ‐enkephalin‐OMe competed for the binding sites of [ 3 H]naloxone as potently as DALE did; IC 50 values for both compounds were 50 nM. Mel substitution has led to one order potency decrease in binding to the δ‐sites. 0.5–1 μM of the compound irreversibly inactivates 50% of the binding sites of [ 3 H]naloxone, and 5–10 μM of that of [ 3 H]DALE. These results shed new light on the structural requirements established for opioid peptides. In addition, the new derivative can be used as an affinity label of the opioid receptor.