Nachman R J, Holman G M, Haddon W F, Hayes T K
Laboratory for Invertebrate Neuroendocrinology, Texas A&M University.
Pept Res. 1989 Mar-Apr;2(2):171-7.
The sulfakinins constitute a family of real and putative peptide sequences characterized from the cockroach Leucophaea maderae (leucosulfakinin subfamily) and fruitfly Drosophila melanogaster (drosulfakinin subfamily) with homology to the sulfated mammalian hormones gastrin II and cholecystokinin (CCK). The leucosulfakinin (LSK) subfamily of neuropeptides stimulate contractions of the isolated cockroach hindgut. In this paper, we have ascertained some of the primary structural requirements of the sulfakinins for myotropic (muscle-contracting) activity. The myotropic "active core" of this family has been determined to be the C-terminal hexapeptide, though the C-terminal octapeptide (Glu-Asp-Tyr(SO3H)-Gly-His-Met-Arg-Phe-NH2) is required for full activity. The LSKs demonstrate considerable tolerance to Ala substitution in positions 7 and 9 within the active core without complete loss of activity. Conversely, Ala substitution in positions 8, 10 and 11 led to inactive compounds. Basicity is a critical feature of LSK position 10, while aromatic character is an important characteristic for positions 8 and 11 for myotropic activity. Only trace activity could be observed upon replacement of the Tyr(SO3H) residue in LSK-position 6 with a Ser(SO3H). One analog ([3MeHis8] LSK) proved more active as a contractile stimulant than the natural product, while another ([7-11,Tyr(SO3H)7] LSK), conversely, demonstrated inhibition of spontaneous contractions of the cockroach hindgut.
速激肽构成了一类已确定和推测的肽序列家族，其来源于德国蜚蠊（亮氨酸速激肽亚家族）和黑腹果蝇（果蝇速激肽亚家族），与硫酸化的哺乳动物激素胃泌素II和胆囊收缩素（CCK）具有同源性。神经肽的亮氨酸速激肽（LSK）亚家族可刺激离体蟑螂后肠收缩。在本文中，我们确定了速激肽对促肌（肌肉收缩）活性的一些一级结构要求。尽管该家族的促肌“活性核心”已确定为C端六肽，但完整活性需要C端八肽（Glu-Asp-Tyr(SO3H)-Gly-His-Met-Arg-Phe-NH2）。LSK在活性核心的第7和第9位对丙氨酸取代表现出相当大的耐受性，而活性不会完全丧失。相反，在第8、10和11位进行丙氨酸取代会导致化合物无活性。碱性是LSK第10位的关键特征，而芳香性是第8和第11位对促肌活性的重要特征。用Ser(SO3H)取代LSK第6位的Tyr(SO3H)残基时，只能观察到微量活性。一种类似物（[3MeHis8]LSK）作为收缩刺激剂比天然产物更具活性，而另一种类似物（[7-11,Tyr(SO3H)7]LSK）则相反，表现出对蟑螂后肠自发收缩的抑制作用。
