Lazarus L H, Perrin M H, Brown M R, Rivier J E
J Biol Chem. 1977 Oct 25;252(20):7180-3.
Systematic substitution of the natural L-amino acids in neurotensin by their D isomers reveals that the COOH-terminal portion of this tridecapeptide is required for binding to mast cell receptors: D-amino acid replacements from Pro10 through Leu13 substantially decrease that binding. Either blockage of the COOH-terminal carboxyl group as with N-methylamidation, or formation of a cyclic structure by the inclusion of a disulfide bond, a Cys2,13 substitution, markedly reduces the specific binding to mast cell receptor sites. Modifications in the NH2-terminal portion of neurotensin do not affect the binding to mast cells. However, D-Arg8 and D-Arg9 substitutions increase binding by factors of 5- to 6-fold. The hydroxyl group at position 3 or 11 is not essential for binding since Phe3 or Phe11 is equivalent to Tyr3 or Tyr11. The COOH-terminal penta- and hexapeptides are able to displace approximately 70% 125I-neurotensin relative to the intact peptide. Of 18 other biologically active peptides tested, only xenopsin, a naturally occurring COOH-terminal analog of neurotensin, and bradykinin effectively compete in the binding assay to an extent of 60 and 100%, respectively. Histamine, diphenhydramine, and noradrenaline are ineffective in this regard.
用神经降压素的D型异构体系统取代其天然L型氨基酸，结果显示该十三肽的COOH末端部分是与肥大细胞受体结合所必需的：从Pro10到Leu13的D型氨基酸取代显著降低了这种结合。与N-甲基酰胺化一样阻断COOH末端羧基，或通过引入二硫键（Cys2,13取代）形成环状结构，均会显著降低与肥大细胞受体位点的特异性结合。神经降压素NH2末端部分的修饰不影响与肥大细胞的结合。然而，D-Arg8和D-Arg9取代使结合增加了5至6倍。3位或11位的羟基对于结合并非必需，因为Phe3或Phe11等同于Tyr3或Tyr11。相对于完整肽，COOH末端五肽和六肽能够取代约70%的125I-神经降压素。在测试的18种其他生物活性肽中，只有异速激肽（神经降压素的一种天然存在的COOH末端类似物）和缓激肽在结合试验中能有效竞争，竞争程度分别为60%和100%。组胺、苯海拉明和去甲肾上腺素在这方面无效。
