Mechanisms accelerating tachykinin's biological activities

天然和合成速激肽的生物活性在氨基酸序列中受到精心控制。尤其是末端氨基酸甲硫酰胺(M-NH2)和C端五肽中的苯丙氨酸(F)对于保持速激肽的活性和作为NK受体的地址域是必不可少的。然而，不仅在C-末端，在N-末端也有许多其他的调节机制。当C端七肽有较强的活性时，N端起抑制作用，副VISA。此外，生物活性的强弱在很大程度上取决于氨基酸序列中5、6和8位的三个氨基酸的结合方式。D型氨基酸也可被L型氨基酸取代。最近确定了具有最强唾液活性的九肽(QKQQFYGLM-NH2)，但它的二聚体对唾液没有任何效果。我们已经使用了许多合成的速激肽来寻找唾液的活性部位。但是，要阐明如何控制活性部位是非常复杂的。不幸的是，九肽太短，无法用高科技机器确定二级或三级结构。

The biological activities of natural and synthetic tachykinins are elaborately controlled in the amino acid sequence. Especially methionylamide (M-NH2), a terminal amino acid, and phenylalanine (F) including in a C-terminal pentapeptide are essential to keep tachykinin's activities and to work as an address domain for the NK receptors. However, there are many other regulatory mechanisms in not only C-terminals but N-terminals. When a C-terminal heptapeptide has strong activity, the N-terminals work inhibitedly and vice visa. In addition, the intensity of biological activities are drastically dependent on the combination mode of three amino acids in positions 5, 6 and 8 present in amino acid sequence. The D-type amino acids are also replaceable with L-type ones. The nonapeptide (QKQQFYGLM-NH2) with the strongest activities for salivation has newly been determined, but its dimmer does not show any effectiveness for salivation. We have carried out using many synthetic tachykinins to find out the active site for salivation. But, it is very complicated to elucidate how to control the active site. Unfortunately the nonapeptide was too short to determine the secondary or tertiary structure with a high technology machine.