Sasaki Y, Ambo A, Suzuki K
Tohoku College of Pharmacy, Sendai, Japan.
Biochem Biophys Res Commun. 1991 Oct 31;180(2):822-7. doi: 10.1016/s0006-291x(05)81138-6.
Nine [D-Ala2]deltorphin II (DL-II:Tyr-D-Ala-Phe-Glu-Val-Val-Gly-NH2) analogs having various aliphatic amino acids at positions 5 and 6 were synthesized to gain more information about the role of hydrophobic Val5,6 residues for the delta-opioid receptor selectivity. Binding assays of analogs replaced by Ala demonstrated the importance of hydrophobic Val5,6 residues in DL-II for delta-affinity and selectivity, and especially critical importance of Val5 residue for higher delta-selectivity. By enhancing the hydrophobicity of residues at positions 5 and 6, we have developed analogs with very high delta-affinity and selectivity over those of DL-II, e.g., [Ile5,6], [norleucine5,6] and [gamma-methyl-leucine5,6]DL-II, which will be useful as delta-selective ligands for investigation of the physiological role of opioid receptors.
合成了9种在第5位和第6位具有不同脂肪族氨基酸的[D - Ala2]强啡肽II（DL - II：Tyr - D - Ala - Phe - Glu - Val - Val - Gly - NH2）类似物，以获取更多关于疏水的Val5,6残基对δ-阿片受体选择性作用的信息。用丙氨酸取代类似物的结合试验证明了DL - II中疏水的Val5,6残基对δ-亲和力和选择性的重要性，尤其是Val5残基对更高δ-选择性的至关重要性。通过增强第5位和第6位残基的疏水性，我们开发出了比DL - II具有更高δ-亲和力和选择性的类似物，例如[Ile5,6]、[正亮氨酸5,6]和[γ-甲基-亮氨酸5,6]DL - II，它们将作为δ-选择性配体用于研究阿片受体的生理作用。
