IMMUNOLOGICAL AND BIOLOGICAL-ACTIVITIES OF FRAGMENTS AND ANALOGS OF BRADYKININ
IMMUNOLOGICAL AND BIOLOGICAL-ACTIVITIES OF FRAGMENTS AND ANALOGS OF BRADYKININ
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DOI：
10.1139/o79-067
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发表时间：
1979-01-01
期刊：
影响因子：
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通讯作者：
TUSTANOFF, ER
中科院分区：
文献类型：
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作者：
REDMAN, LW;REGOLI, D;TUSTANOFF, ER
使用一些类似物和片段的短链肽缓激肽，进行了一系列的实验，以评估其亲肌性和免疫反应性的性质的母体分子的基本结构的修改的效果。结合动力学的抗体提出了真正的九肽和它的特定的生物受体中发现的豚鼠回肠被用来研究这些改变的影响。缓激肽的肽衍生物与延伸在N-末端（赖氨酸和蛋氨酸-赖氨酸-缓激肽）交叉反应的抗体提出缓激肽59和70%，分别。具有完整C-末端的内部片段（2-9和3-9缓激肽）与该相同抗体的反应程度分别为250%和875%，表明它们是比血管加压素分子本身更有效的抗原。其他内部片段以及9-取代的类似物有效地不相互作用。缓激肽的C末端Arg在与其抗体的结合机制中确实是必不可少的。这反过来又说明了载体卵清蛋白在卵清蛋白-甲苯-二异氰酸酯-缓激肽复合物抗血清开发中的作用。豚鼠生物测定制剂的生理学实验得出了类似的结论。缓激肽的大多数内部片段没有活性，而N-末端片段（2-9、3-9和5-9缓激肽）保留了一些活性，再次表明在分子的C-末端需要完整的Arg残基。位置9的任何修饰都会导致生物活性的严重损害。因此，缓激肽的C-末端残基必须是保守的分子，以保持其免疫和生理活性。本网站的任何扩展、删除或修改都将严重影响这些功能。
Using a number of analogs and fragments of a short-chain peptide bradykinin, a series of experiments were carried out to assess the effect of modifications to the basic structure of the parent molecule on its myotropic and immunoreactive properties. Binding kinetics of both an antibody raised against the authentic nonapeptide and its specific biological receptor found in the guinea pig ileum were used to study these alteration effects. Peptide derivatives of bradykinin with an extension at the N-terminal (Lys- and Met-Lys-bradykinin) cross-reacted with the antibody raised to bradykinin 59 and 70%, respectively. Internal fragments with intact C-termini (2-9 and 3-9 bradykinin) react with this same antibody to an extent of 250 and 875%, respectively, indicating that they are more potent antigens than the vasopressor molecule itself. Other internal fragments, as well as 9-substituted analogs effectively did not interact. The C terminal Arg of bradykinin is indeed essential in the binding mechanism with its antibody. This in turn illustrates the role of the carrier ovalbumin in the development of antiserum to the ovalbumim-toluene-diisocyanate-bradykinin complex. The physiological experiments with the guinea pig bioassay preparations led to similar conclusions. Most internal fragments of bradykinin were devoid of activity, whereas N-terminal fragments (2-9, 3-9, and 5-9 bradykinin) retained some activity again indicating a need for an intact Arg residue at the C-terminus of the molecule. Any modification in position 9 results in severe impairment of biological activity. Thus, the C-terminal residue of bradykinin must be conserved for the molecule to retain its immunological and physiological activities. Any extensions, deletions or modifications of this site will severely retard these functions.