Preclinical evaluation of a new potent immunosuppressive agent, rapamycin.
Preclinical evaluation of a new potent immunosuppressive agent, rapamycin.
复制标题
新型强效免疫抑制剂雷帕霉素的临床前评估。
DOI：
10.1097/00007890-199108000-00001
复制
发表时间：
1991
期刊：
影响因子：
6.2
通讯作者：
Sehgal,SN
中科院分区：
文献类型：
--
作者：
Kahan,BD;Chang,JY;Sehgal,SN
雷帕霉素 (RAPA) 是一种由吸水链霉菌产生的大环内酯类抗生素，吸水链霉菌是一种放线菌，从复活节岛 Rapa-Nui Vai Atore 地区的土壤样本中分离出来 (1, 2)。 RAPA 是一种 31 元大环内酯（分子量 914.2，C51H79N013），含有不寻常的半缩酮掩蔽 α,β-二酮酰胺部分（与 FK506 中的相似）以及具有独特三烯链段的较大环结构（图 1 [3]）。 RAPA 的碱和酸水解产生独特结构的片段，包括 FK506 中也存在的 L (-) 哌啶酸（哌啶-2-羧酸），以及独特的源自莽草酸的三取代环己烷部分 C39-C45 (4)。溶液中 RAPA 的高场 1H 和 13C 核磁共振谱显示，存在两种构象异构体（比例约为 4:1），由 C-15 处酰胺键的反式-顺式旋转产生 (4)。
Rapamycin (RAPA) is a macrolide antibiotic produced by Streptomyces hygroscopicus, an actinomycete that was isolated from a soil sample obtained from the Vai Atore region of Rapa-Nui, the Easter Island (1, 2). RAPA is a 31-membered macrocyclic lactone (molecular weight 914.2, C51H79N013) containing the unusual hemiketal masked [alpha],[beta]-diketo amide moiety (similar to that present in FK506) as well as a larger ring structure with a unique triene segment (Fig. 1 [3]). Alkaline and acid hydrolysis of RAPA yield fragments of unique structure, including L (-) pipecolic acid (piperidine-2-carboxylic acid), which is also present in FK506, and a distinctive, shikimic acid-derived trisubstituted cyclohexane moiety C39-C45 (4). High-field 1H and 13C nuclear magnetic resonance spectra of RAPA in solution show two conformational isomers (present in an approximate ratio of 4: 1), produced by trans-cis rotation of an amidic bond at C-15 (4).