本論文主要係以分子動力學模擬方法，並搭配量子化學半經驗方法中的AM1計算，來研究類鴉片系統中的配體結構與活性關係，藉以探討其與受體間的結合交互作用機制。對於嚴重的疼痛而言，嗎啡是最廣泛使用的止痛劑，但其在使用過程中會伴隨產生一些副作用。且自從發現人體內存在符合類鴉片受體的內源性物質─「腦啡」後，開發新鎮痛藥物一直以朝向尋找成癮性小且副作用少為努力的目標。由於人體中存在的類鴉片系統，除了具有止痛、鎮靜與欣快的作用外，還會影響情緒、記憶與認知等心理或生理層面。而這些作用便是起源於類鴉片配體與受體結合後所導致的一連串生化調控機制。由於受體本身是一個巨大的膜蛋白，要直接研究胜分子與受體間的交互作用是非常困難的。因此，直至目前為止，對於藥物設計與間接推測受體的選擇性來說，胜分子的結構研究至今仍是一個相當重要的課題。因此，本論文首先於第二章對類鴉片受體與配體的背景做一介紹，接著，第三章至第五章則分別介紹δ、κ、μ三種類鴉片配體的結構與活性研究。希冀藉由這三種不同屬性之類鴉片配體的藥效基團研究，使我們更能了解及釐清整個類鴉片系統中配體與受體結合時的活性關係。綜合本論文之研究內容，我們分別定義出κ-以及μ-藥效基團模型，並與Shenderovich等人所提出的δ藥效基團模型做一比較。最後，希望透過研究三種不同屬性的類鴉片配體之結構穩定特性與藥理活性，能進而做為爾後在藥物設計與醫療上的參考。

The dissertation directs on studying the structure-activity relationships of the various opioid ligands using molecular dynamics simulations and AM1 calculations in order to understand the mechanisms of the active binding interactions between opioid receptors and ligands. It is clear known that morphine is widely used in medicine as strong analgesics for relief of severe pain. Yet, it may cause addiction and withdrawal symptoms as well as other harmful effects. Therefore, since the endogenous opioid peptide of the enkephalin was discovered corresponding to the opioid receptor, the efforts of developing the new analgesic drugs have been toward minimizing a risk of addiction and reducing adverse side effects. Due to the existence of the opioid system in humans, in terms of its functions not only possess analgesia, sedation, and euphoria, but influence of the psychological and physiological levels involve the emotion, memory, and recognition. All of the above-mentioned functions result from a series of biochemical regulations after the binding interactions between opioid receptors and their ligands. Because opioid receptors are large membrane proteins, difficult to study by standard structural techniques. Thus, conformational studies of opioid peptides are still important for drug design and also for indirect receptor mapping. We first introduce a number of backgrounds for opioid receptors and opioid ligands. Subsequently, the structure-activity relationships of δ-, κ- and μ-selective opioid ligands are studied. We hope such investigations can let us more understand the structure-activity relationships of opioid system. In this dissertation, we have well defined the pharmacophore model of κ- and μ-opioid receptor, respectively. These significant results have compared to δ pharmacophore model. Finally, the results of this dissertation will provide some valuable information for drug design and clinical therapy.

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