The structure of an endomorphin analogue incorporating 1-aminocyclohexane-1-carboxlylic acid for proline is similar to the beta-turn of Leu-enkephalin.

Endomorphin (EM2, Tyr-Pro-Phe-Phe-NH(2)) can assume various conformations related to cis/trans-rotamers of the amide linkage of Tyr-Pro. To control isomerization, restricted or flexible components have been introduced at the Pro position. We focused on [Chx(2)]EM2, an EM2 analogue substituting 1-aminocyclohexane-1-carboxlylic acid (Chx) for Pro. X-ray diffraction analysis revealed that [Chx(2)]EM2 is folded into the trans-form of Tyr-Chx. The manner of folding resembled that seen in D-TIPP, an EM analogue incorporating tetrahydroisoquinoline carboxylic acid, as well as the beta-turn of Leu-enkephalin. Selectivity for the opioid mu-receptor was fairly well conserved by [Chx(2)]EM, suggesting that the folded form is important for mu-selectivity.