NMDA 受體的超活化，是造成中風以及許多?經退化性疾病(包括??癡呆症，帕?森氏或亨廷頓氏病) 的原因。 目前已開發出許多的NMDA 受體拮抗劑，但大多?具有可以使其穿透血腦屏障的生?特性。 可能解決此問題的一種方法為 - ?用某個能與腦血管內皮細胞表面作用、並且在?破壞細胞膜功能下卻能穿過膜的特定的配體(?如胜?), 經由化學偶?的方式將此配體結合上藥物，這些藥物?可望成功傳遞到大腦。在本提案中，我們將合成?用經由噬菌體篩選系統(Phage Display)篩選出能夠通過血腦屏障之胜?，並合成胜?與NMDA 受體拮抗劑之化合物，藉以評估?用這些胜?作為NMDA 受體拮抗劑通過血腦屏障之傳遞載體的潛在能?。 Hyperactivation of N-Methyl-D-aspartate (NMDA) receptors results in excitotoxicity, contributing to damage in stroke and neurodegenerative disorders including Alzheimer’s, Parkinson’s or Huntington’s diseases. Many NMDAR antagonists have been developed thus far, but majority of these antagonists have poor physicochemical properties for adequately penetrating the blood–brain barrier (BBB). One approach to solve this problem is to search for specific ligands (such as peptides) that are able to interact with the cell surface of the brain endothelial cells and across the plasma membrane without disrupting the membrane activity. By chemically conjugated to the drug, the drugs can hopefully be successfully delivered to the brain. In this proposal, we intended to synthesize BBB permeable peptides that were screened from phage display system and evaluate the potential of these peptides as NMDAR antagonists delivery vector through blood brain barrier.
