Edwards J V, Spatola A F, Lemieux C, Schiller P W
Biochem Biophys Res Commun. 1986 Apr 29;136(2):730-6. doi: 10.1016/0006-291x(86)90500-0.
The peptide bond in the 4-5 position of the cyclic and linear enkephalin analogs H-Tyr-cyclo[-D-Lys-Gly-Phe-L(or D)-Leu-] and H-Tyr-D-Ala-Gly-Phe-L(or D)-Leu-OH was replaced by a thiomethylene ether linkage. Each of the configurational isomers of the cyclic pseudopeptide H-Tyr-cyclo[-D-Lys-Gly-Phe psi [CH2S]L(or D)-Leu-] showed high potency in both the guinea pig ileum and the mouse vas deferens assay and, therefore, had no preference for either mu- or delta-opioid receptors, in contrast to the cyclic parent peptides H-Tyr-cyclo[-D-Lys-Gly-Phe-L(or D)-Leu-] which are mu-receptor selective. The loss of selectivity observed with the cyclic pseudopeptides may be due to the greater flexibility of their 18-membered ring structures as a consequence of the peptide bond substitution. The linear pseudopeptide analogs were both less potent and less delta-receptor selective than their parent compounds. These results indicate that thiomethylene ether peptide bond replacements can have a pronounced effect on the activity profile of peptide hormones and neurotransmitters.
环型和线型脑啡肽类似物H-Tyr-环[ -D-Lys-Gly-Phe-L（或D）-Leu- ]及H-Tyr-D-Ala-Gly-Phe-L（或D）-Leu-OH中4-5位的肽键被硫亚甲基醚键取代。环型假肽H-Tyr-环[ -D-Lys-Gly-Phe ψ [CH2S]L（或D）-Leu- ]的每种构型异构体在豚鼠回肠和小鼠输精管试验中均显示出高效能，因此，与选择性作用于μ-阿片受体的环型母体肽H-Tyr-环[ -D-Lys-Gly-Phe-L（或D）-Leu- ]不同，该假肽对μ-或δ-阿片受体均无偏好性。环型假肽选择性的丧失可能是由于肽键取代导致其18元环结构具有更大的灵活性。线型假肽类似物与其母体化合物相比，效能更低且对δ-受体的选择性更弱。这些结果表明，硫亚甲基醚肽键取代可对肽类激素和神经递质的活性特征产生显著影响。
