Conformation of cyclic analogs of enkephalin. II. Analogs containing a cystine bridge

A systematic survey has been made, using molecular mechanics, of the conformation of the ring entity of the enkephalin analogs, [ D ‐Cys 2 ‐ L ‐Cys 5 ]‐enkephalinamide and [ D ‐Cys 2 ‐ D ‐Cys 5 ]enkephalinamide. These molecules are considerably more flexible than the analog Tyr‐ cyclo ( N γ ‐ D ‐A 2 bu‐Gly‐Phe‐Leu‐), but the favored conformations of all three are very similar. The results of these studies are compatible with a Gly 3 ‐Phe 4 type II′ bend in the active conformation of enkephalin.