Bungart D, Kegel G, Burdzik S, Keller R
Institut für Zoophysiologie, Universität Bonn, Germany.
Peptides. 1995;16(2):199-204. doi: 10.1016/0196-9781(94)00187-1.
Orcokinin (OK, NFDEIDRSGFGFN) was recently identified from the crayfish, Orconectes limosus, as a potent hindgut-stimulating factor (14). To assess the importance of structural features of the peptide involved in effective ligand-receptor interactions, synthetic analogues of orcokinin were tested in the hindgut bioassay. Tests with N- and C-terminal-truncated analogues and the C-terminal-amidated analogue (OK-NH2) demonstrate that changes at the C-terminus interfere less with biological activity than changes at the N-terminus. Removal of more than one amino acid at the N-terminus resulted in a complete loss of activity, whereas the C-terminal deletion of three amino acids still produced an analogue with full intrinsic activity but with a drastic shift in threshold concentration of activity from 1 x 10(-10) to 1 x 10(-7) M. Deletion of four amino acids at the C-terminus resulted in a completely inactive analogue. The C-terminal hydroxyl group does not seem to be important because amidation (OK-NH2) resulted in almost no loss of activity. Replacing Arg7 with Ala produced an analogue almost equipotent to orcokinin. Replacement of Phe2 by Tyr resulted in considerable loss of activity. An important role of Phe2 is further suggested by the steep drop of activity after removal of this residue in the N-terminal-deleted analogues.
最近从小龙虾奥氏螯虾中鉴定出一种名为奥虫激肽（OK，NFDEIDRSGFGFN）的强力后肠刺激因子（14）。为了评估该肽参与有效配体 - 受体相互作用的结构特征的重要性，在小龙虾后肠生物测定中对奥虫激肽的合成类似物进行了测试。对N端和C端截短类似物以及C端酰胺化类似物（OK - NH2）的测试表明，C端的变化对生物活性的干扰小于N端的变化。N端去除一个以上氨基酸会导致活性完全丧失，而C端缺失三个氨基酸仍能产生具有完全内在活性的类似物，但活性阈值浓度从1×10（-10）急剧转变为1×10（-7）M。C端缺失四个氨基酸会产生完全无活性的类似物。C端羟基似乎并不重要，因为酰胺化（OK - NH2）几乎不会导致活性丧失。用丙氨酸取代精氨酸7产生的类似物与奥虫激肽几乎等效。用酪氨酸取代苯丙氨酸2会导致活性大幅丧失。在N端缺失的类似物中去除该残基后活性急剧下降，进一步表明苯丙氨酸2具有重要作用。
