Melphalan potently substitutes the N‐terminal Tyr of D‐Ala2‐Leu5‐enkephalin methyl ester

FEBS Letters

Di Gleria, Katalin¹  Szücs, Mária²  Medzihradszky, Kálmán¹ 

[1] Central Research Institute of Chemistry of the Hungarian Academy of Sciences, POB 17, Budapest, Hungary;Institute of Biochemistry, Biological Research Center of the Hungarian Academy of Sciences, POB 521, Szeged, Hungary

关键词: Opioid receptor;    New enkephalin analog;    Affinity labeling;   

DOI  :  10.1016/0014-5793(85)80197-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

In search of an affinity label of the opioid receptor, the nitrogen mustard melphalan, Mel, was built into the peptide chain of D-Ala²-Leu⁵-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. Mel¹, Leu⁵-enkephalin-OMe competed for the binding sites of [³H]naloxone as potently as DALE did; IC₅₀ 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 [³H]naloxone, and 5–10 μM of that of [³H]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.

【 授权许可】

Unknown