Enkephalins enzymatic degradation

Over 1000 enkephalin derivatives have now been synthesized, and in some of them it has been possible to increase the analgesic effect with respect to enkephalin 33 37). The enkephalin derivative 18 38) (Sandoz, FK 33-824), in which enzymatic degradation is blocked, has proved to be strongly analgesically active in animals. 

In contract to these eompoynds, the myre conformatlonally constrained [d Pen, D-Cys ]-, [D-Pen. Cys ]-, [0 -Pen, D -Pen ]-, and C)-Pen. Pen ]-enkephalins exhibit exceptional 6 receptor selectivity. Conformational differences associated with the Pen residues appear to be responsible for the high receptor selectivity. Finally, a series of cyclic retro-Inverso enkephalins have been designed to incorporate favorable conformational restriction and Increased resistance to enzymatic degradation. 

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