Spatola A F, Saneii H, Edwards J V, Bettag A L, Anwer M K, Rowell P, Browne B, Lahti R, Von Voigtlander P
Life Sci. 1986 Apr 7;38(14):1243-9. doi: 10.1016/0024-3205(86)90416-9.
An isomeric series of four leucine-enkephalin analogs containing the thiomethylene ether unit as an amide bond replacement in all positions have been prepared by solid phase methods. The resulting pseudopeptides divulged widely differing retentive behaviors on reversed phase high performance liquid chromatography (HPLC). An analog containing the Phe psi[CH2S]Leu dipeptide replacement at the 4-5 position exhibited binding close to the parent, leucine enkephalin; its guinea pig ileum (GPI) activity was the highest of the analogs tested. Another compound, Tyr psi[CH2S]Gly1-2]-Leu-enkephalin, also displaced 3H-etorphine well in the binding assay, but caused increased contractions in the GPI assay at low concentrations. The Phe psi[CH2S]Leu results are not compatible with the necessity of a beta-turn structure for agonist activity in the GPI assay.
通过固相法制备了一个由四个亮氨酸脑啡肽类似物组成的异构体系列，这些类似物在所有位置都含有硫亚甲基醚单元作为酰胺键替代物。所得的拟肽在反相高效液相色谱（HPLC）上表现出广泛不同的保留行为。在4-5位含有Phe ψ[CH2S]Leu二肽替代物的类似物表现出与母体亮氨酸脑啡肽接近的结合；其豚鼠回肠（GPI）活性是所测试类似物中最高的。另一种化合物，Tyr ψ[CH2S]Gly1-2]-Leu-脑啡肽，在结合试验中也能很好地取代3H-埃托啡，但在低浓度的GPI试验中会引起收缩增加。Phe ψ[CH2S]Leu的结果与GPI试验中激动剂活性需要β-转角结构的观点不一致。
