| Autor: |
H I, Mosberg, R K, Dua, I D, Pogozheva, A L, Lomize |
| Rok vydání: |
1996 |
| Předmět: |
|
| Zdroj: |
Biopolymers. 39(3) |
| ISSN: |
0006-3525 |
| Popis: |
We have previously proposed a model for the delta-opioid receptor binding conformation of the high affinity tetrapeptide Tyr-c[D-Cys-Phe-D-Pen]OH (JOM-13) based on experimental and theoretical conformational analysis of this peptide and a correlation of conformational preferences of further conformationally restricted analogues of this tetrapeptide with their receptor binding affinities. A key element of this model is the requirement that the Phe3 side chain exist in the chi 1 = -60 degrees conformation. Conformational calculations on the residue 3 dehydrophenylalanine analogues of JOM-13 suggest that while the dehydro (Z) phenylalanine analogue can be superimposed easily with the proposed binding conformer of JOM-13, the dehydro(E)phenylalanine analogue cannot. These results lead to the prediction that the dehydro(Z)phenylalanine analogue should display similar delta-receptor binding affinity as JOM-13 while the dehydro(E)phenylalanine analogue is expected to bind less avidly. Synthesis and subsequent opioid receptor binding analysis of the dehydrophenylalanine analogues of JOM-13 confirm these predictions, lending support to the delta-pharmacophore model. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
Plný text