Ultraviolet Resonance Raman Spectroscopic Study on the Conformation of Enkephalin and Binding Mode to Receptors

我们研究了加入到二脲酰胆碱脂质体中的Met-enkephalin、Leu-enkephalin和[Trp^4] Met-enkephalin的紫外（213和240 nm）共振拉曼（UVRR）光谱。基于先前获得的模型化合物数据的光谱分析为脑啡肽与脂质双分子层的结合方式提供了几条重要信息。从大鼠脑中提取并纯化了一种δ型阿片受体。用UVRR和圆二色光谱研究了受体的结构。得到的结果如下：1。上述提到的每一种脑啡肽在水溶液中都以各种扩展构象的集合形式存在，而在脂质结合状态下则呈折叠构象。Tyr侧链插入到膜疏水内部，但Phe侧链位于极性表面区域或暴露于水相。Leu-enkephalin的Tyr插入膜的程度比其他两种要小。Tyr埋得越深，肽的亲和力和活性越高。膜环境被认为对组织中n端Tyr形式的降解起保护作用。阿片受体的主链主要位于β -片结构中，该蛋白不含很多芳香残基，特别是Tyr和Typ。

We have studied the ultraviolet (213- and 240-nm) resonance Raman (UVRR) spectra of Met-enkephalin, Leu-enkephalin, and [Trp^4] Met-enkephalin incorporated into dilauroylphatidylcholine liposomes. The analysis of the spectra based on the data of model compounds obtained previously has provided several pieces of important information on the binding mode of enkephalin to the lipid bilayers. A delta-type opioid receptor has been extracted from rat brain and purified. The structure of the receptor has been investigated by UVRR and circular dichroism spectroscopy. The results obtained are as follows :1. Every enkephalin mentioned above exists as an ensemble of various extended conformers in aqueous solution, whereas it takes a folded conformation in the lipid-bound state.2. The Tyr side chain is inserted into the membrane hydrophobic interior, but the Phe side chain is located in the polar surface region or exposed to the aqueous phase.3. The degree of insertion of Tyr into the membrane is smaller for Leu-enkephalin than the other two.4. The deeper the Tyr is buried, the higher the affinity and activity of the peptide.5. The membrane environment is considered to play a role in protecting the N-terminal Tyr form degradation in tissues.6. The mainchain of the delta-opioid receptor is largely in the beta-sheet structure and the protein does not contain many aromatic residues, particularly Tyr and Typ.