N-hydroxy amides. Part 5. Synthesis and properties of N-hydroxypeptides having leucine enkephalin sequences

Abstract

In order to study the effects of the N-hydroxy amide group, N-hydroxyenkephalin analogues with the H-Tyr-(HO)X-Gly-Phe-Leu-OH sequence, where X = Gly, L-Ala, or β-Ala, have been synthesized. A ¹H n.m.r. study indicates that the N-hydroxyenkephalins have a type I β-turn structure in dimethyl sulphoxide solution. From the interaction of (HO)Gly- and β-(HO)Ala-analogues with Cu^II it is suggested that the hydroxyamide function exerts a definite influence on the complexation. These N-hydroxy enkephalins are resistant to aminopeptidase M. A qualitative analgesia test shows that the (HO)Ala-analogue possesses a more lasting potency than that of Leu⁵-enkephalin, while having a comparable activity.