Lopes Sílvia C D N, Soares Cláudio M, Baptista António M, Goormaghtigh Erik, Cabral Benedito J Costa, Castanho Miguel A R B
Centro de Química-Física Molecular, Instituto Superior Técnico, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.
J Phys Chem B. 2006 Feb 23;110(7):3385-94. doi: 10.1021/jp053651w.
The analgesic dipeptide kyotorphin (L-Tyr-L-Arg) and an acylated kyotorphin derivative were studied by a combination of theoretical (molecular dynamics simulation and quantum mechanics methods) and experimental (fluorescence and infrared spectroscopies) approaches both in solution and in model systems of membranes. At biological pH the peptides have a neutral net charge. Nevertheless, their phenolic rings interact with phospholipid molecules (partition coefficient varies from 6 x 10(2) to 2 x 10(4), depending on the lipid and pH used) despite being exposed to the aqueous bulk medium. The lowest energy transition dipole moment is displaced from the normal to the lipid bilayer by 20 degrees on average. The observed extensive interaction, pK(a), precise location, and well-defined orientation in membranes combined with the ability to discriminate rigid raftlike membrane domains suggest that kyotorphin meets the structural constraints needed for receptor-ligand interaction. The acylated kyotorphin derivative mimics kyotorphin properties and represents a promising way for entrapment in a drug carrier and transport across the blood-brain barrier.
通过理论方法（分子动力学模拟和量子力学方法）与实验方法（荧光光谱和红外光谱）相结合，在溶液和膜模型系统中对镇痛二肽京都啡肽（L-酪氨酸-L-精氨酸）及其酰化京都啡肽衍生物进行了研究。在生理pH值下，这些肽具有中性净电荷。然而，尽管它们暴露于大量水性介质中，但其酚环仍与磷脂分子相互作用（分配系数在6×10²至2×10⁴之间变化，具体取决于所用的脂质和pH值）。最低能量跃迁偶极矩平均偏离脂质双层法线20度。在膜中观察到的广泛相互作用、pK(a)、精确位置和明确取向，以及区分刚性筏状膜结构域的能力，表明京都啡肽满足受体-配体相互作用所需的结构限制。酰化京都啡肽衍生物模拟了京都啡肽的性质，是一种有前景的被药物载体包裹并穿过血脑屏障的方式。
