Velentza A, Spiliou S, Poulos C P, Goldsworthy G J
Department of Chemistry, University of Patras, 26500, Patras, Greece.
Peptides. 2000 May;21(5):631-7. doi: 10.1016/s0196-9781(00)00200-x.
Several structural characteristics in the molecule of the locust adipokinetic hormone, AKH-I, have been investigated in terms of their importance in determining biologic activity. All modifications tested in this study resulted in analogues with decreased potency in comparison with the parent molecule. However, all analogues that were found to be active gave a full response, although often only at very high doses of peptide. This study has highlighted for the locust receptor(s) the vital role of the side chain of Thr(5), and the importance of positions 4 and 8. For example, when Trp(8) and Phe(4) were exchanged, the resulting analogue (Trp(4),Phe(8)-AKH-I) was one of the least active analogues tested in this study. Although Trp is tolerated quite well as a substitute for Phe(4), with only a 10-fold loss of potency, Phe is not favored as a substitute for Trp(8) (>300 times decrease in potency). On the other hand, 3-[2-napthyl] alanine (Nal) is a better substitute for Trp(8) (only a 100-fold loss in potency). We conclude that position 4 requires a phenyl ring in the side chain, and position 8 an indole ring.
对蝗虫脂肪动激素AKH-I分子中的几个结构特征在决定生物活性方面的重要性进行了研究。本研究中测试的所有修饰都导致类似物与母体分子相比活性降低。然而，所有被发现有活性的类似物都能产生完全反应，尽管通常仅在非常高的肽剂量下。这项研究突出了苏氨酸（5）侧链对蝗虫受体的重要作用，以及第4位和第8位的重要性。例如，当色氨酸（8）和苯丙氨酸（4）交换时，得到的类似物（色氨酸（4），苯丙氨酸（8）-AKH-I）是本研究中测试的活性最低的类似物之一。虽然色氨酸作为苯丙氨酸（4）的替代物耐受性相当好，活性仅损失10倍，但苯丙氨酸作为色氨酸（8）的替代物则不受青睐（活性降低>300倍）。另一方面，3-[2-萘基]丙氨酸（Nal）是色氨酸（8）更好的替代物（活性仅损失100倍）。我们得出结论，第4位需要侧链中有一个苯环，第8位需要一个吲哚环。
