Synthesis and biological activity of (D)Ala2, Leu5-enkephalins containing hydrophilic or hydrophobic moieties

The synthesis in solution of some modified (D)Ala²,Leu⁵-enkephalins has been carried out. The lipophilic properties of the parent compound have been modified by amidation of the carboxyl function with alkylamines of increasing hydrophilicity to increase permeability of the blood-brain barrier. Attempts to reduce enzymatic degradation have been carried out either by reductive glucosamination or by amidation of the carboxyl function with 2-amino-2-deoxy-β-D-glucopyranose. Esterification of the carboxyl function of (D)Ala²,Leu⁵-enkephalin with polyethylenglycole 1000 has also been carried out. The effects induced by these modifications have been evaluated by in vitro and in vivo tests.