首页    期刊浏览 2024年10月06日 星期日
登录注册

文章基本信息

  • 标题:Contractile activities of structural analogs of leukotrienes C and D: role of the polar substituents
  • 本地全文:下载
  • 作者:R A Lewis ; J M Drazen ; K F Austen
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:1981
  • 卷号:78
  • 期号:7
  • 页码:4579-4583
  • DOI:10.1073/pnas.78.7.4579
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:Twenty-three structural analogs of the leukotriene components of slow reacting substance of anaphylaxis (SRS-A), in which the polar regions of the leukotriene were systematically modified, were tested for their contractile activities on guinea pig pulmonary parenchymal strips and guinea pig ileum. The structural modifications allowed evaluation of the separate contributions of the four polar units in the C-1 to C-6 region of the SRS-A leukotrienes to smooth muscle spasmogenic activity. The free NH2-terminal amino group of the S-linked peptide was necessary for full activity, and its deletion or substitution reduced activity by more than one but less than two orders of magnitude. A similar level of importance was apparent for the free glycine carboxyl group. In contrast, a free eicosanoid carboxyl at C-1 is not required for full activity on the airway and for substantial activity on the ileum. A role for the C-5 hydroxyl is indicated by the inactivity of the one available 5-desoxy analog. Nucleophilic, divalent sulfur is not critical to leukotriene D (LTD) activity, in that one sulfoxide had substantial function. The conformational relationship between the eicosanoid and peptide moieties of LTD is of considerable importance in that epimers at the C-5 or C-6 position were less active than LTD by more than two orders of magnitude. Several lines of evidence suggest that the relative geometrical arrangement of the C20 chain and the peptide unit is important to activity, consistent with the existence of a true receptor for LTD.
国家哲学社会科学文献中心版权所有