具有共价连接脂质的腺苷类似物在A1-腺苷受体上具有增强的效力。
Adenosine analogs with covalently attached lipids have enhanced potency at A1-adenosine receptors.
作者信息
Jacobson K A, Zimmet J, Schulick R, Barone S, Daly J W, Kirk K L
机构信息
Laboratory of Chemistry, NIDDK, Bethesda, MD 20892.
出版信息
FEBS Lett. 1987 Dec 10;225(1-2):97-102. doi: 10.1016/0014-5793(87)81138-9.
Abstract
Chemically functionalized congeners of N6-phenyladenosine and 1,3-dipropyl-8-phenylxanthine have been covalently coupled to fatty acids, diglycerides, and a phospholipid. The lipid-drug conjugates inhibit R-[3H]-phenylisopropyladenosine binding to A1-adenosine receptors in rat cerebral cortex membranes. A xanthine-phosphatidylethanolamine conjugate bound with a Ki value of 19 nM. Various xanthine esters of low potency are potential prodrugs. Amides of an adenosine amine congener (ADAC) with 18-carbon fatty acids exhibited Ki values at A1-adenosine receptors of 70 pM, representing a 130-fold enhancement over the affinity of the corresponding acetyl amide. The very high affinity of adenosine-lipid conjugates may be due to stabilization of these adducts in the phospholipid microenvironment of the receptor protein.
摘要
N6-苯基腺苷和1,3-二丙基-8-苯基黄嘌呤的化学官能化类似物已与脂肪酸、甘油二酯和磷脂共价偶联。脂质-药物缀合物抑制R-[3H]-苯基异丙基腺苷与大鼠大脑皮层膜中A1-腺苷受体的结合。一种黄嘌呤-磷脂酰乙醇胺缀合物的结合Ki值为19 nM。各种低效的黄嘌呤酯是潜在的前药。腺苷胺类似物（ADAC）与18碳脂肪酸的酰胺在A1-腺苷受体处的Ki值为70 pM，比相应乙酰酰胺的亲和力提高了130倍。腺苷-脂质缀合物的极高亲和力可能是由于这些加合物在受体蛋白的磷脂微环境中得到稳定。
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