Contractile activities of structural analogs of leukotrienes C and D: necessity of a hydrophobic region.
Contractile activities of structural analogs of leukotrienes C and D: necessity of a hydrophobic region.
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白三烯 C 和 D 结构类似物的收缩活性：疏水区域的必要性。
DOI：
10.1073/pnas.78.5.3195
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发表时间：
1981
影响因子：
11.1
通讯作者：
E. J. COREYt
中科院分区：
文献类型：
--
作者：
J. M. Drazen;Robert A. LEWISt;K. F. AUSTENt;M. Toda;Francis BRIONf;Anthony MARFATf;E. J. COREYt
研究了白三烯C和D的16种结构类似物在豚鼠肺实质条和回肠上的收缩活性。这些类似物与天然结构的不同之处在于硫醚连接的肽侧链或羟基（或两者都有）的位置或乙烯键的数量和位置。在两种平滑肌制剂中，硫醚连接肽链而不是在C-6位置连接的类似物的活性都显著降低，而在两种试验中，各种乙烯键饱和的类似物保留了大量的收缩活性。这些观察结果表明，尽管类二十烷酸的疏水区域对于收缩活性是必要的，但该区域的长度比其精确的立体化学更为关键。以8-、11-和15-氢过氧二十碳四烯酸为前体，基于平行生物合成路线的白三烯类似物被发现影响相对较弱的收缩反应，因此它们在这方面作为生物制剂的作用似乎不太可能。
Sixteen structural analogs of leukotrienes C and D were tested for their contractile activities on guinea pig pulmonary parenchymal strip and ileum. The analogs differed from the native structures in the position of either the thioether-linked peptide side chain or the hydroxyl group (or both) or in the number and positions of ethylenic bonds. Analogs in which the thioether-linked peptide chain was attached other than at the C-6 position had substantial reductions in activity on both smooth muscle preparations, whereas analogs in which the various ethylenic bonds were saturated retained substantial contractile activity in both assays. These observations demonstrate that, although a hydrophobic region of the eicosinoid is necessary for contractile activity, the length of this segment is more critical than its precise stereochemistry. Analogs of leukotrienes based on the possibility of parallel biosynthetic routes deriving from 8-, 11-, and 15-hydroperoxyeicosatetraenoic acid as precursors were found to effect a comparatively weak contractile response so that their role as biological agents in this respect seems unlikely.