Synthesis of leucine enkephalin derivatives: Structure-function studies

The solid phase synthesis of highly purified [Leu⁵] enkephalin and of seven derivatives including [Ala²,Leu⁵]-, [Ser²,Leu⁵]-, [Ser³,Leu⁵]-, [Aba²,Leu⁵]-, and [des-Gly²⁽³⁾,Leu⁵]enkephalins are reported, and their morphine-like activities in neuroblastoma x glioma cell homogenates were measured. Changes at the 2, 3, and 5 positions of the enkephalin provided analogues which were all less active than [Leu⁵] enkephalin. The results are discussed in terms of recently suggested conformational structures for the enkephalin peptides. No melanocyte stimulating activity was observed for [Leu⁵] enkephalin, [Ala²,Leu⁵]enkephalin, or [Ser²,Leu⁵] enkephalin.