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.
Doi
Mitsunobu
M
Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan. doit@gly.oups.ac.jp
Asano
Akiko
A
Komura
Eri
E
Ueda
Yoko
Y
D000598:Amino Acids, Cyclic / Q000737:chemistry*; D003509:Cyclohexanecarboxylic Acids / Q000737:chemistry*; D004743:Enkephalin, Leucine / Q000737:chemistry*; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry*; D011392:Proline / Q000737:chemistry; D017433:Protein Structure, Secondary
D000598:Amino Acids, Cyclic; D003509:Cyclohexanecarboxylic Acids; D009842:Oligopeptides; C105293:endomorphin 1; C014966:1-aminocyclohexanecarboxylic acid; D004743:Enkephalin, Leucine; D011392:Proline