Ivanova D M, Vilenskiĭ D A, Levitskaia N G, Andreeva L A, Alfeeva L Iu, Kamenskiĭ A A, Miasoedov N F
Izv Akad Nauk Ser Biol. 2006 Mar-Apr(2):204-10.
Melanocortins, peptides of the family of adrenocorticotropic (ACTH) and melanocyte-stimulating (MSH) hormones, have a wide range of physiological activity. Heptapeptide semax (MEHFPGP) is an analog of the ACTH4-10 fragment. Previously, pronounced nootropic and neuroprotective activities were shown for this peptide; in addition, it decreases pain sensitivity in animals. In this work, the relationship between analgesic activity of the peptide and its structure was studied. The following analogs of the N-terminal ACTH fragments were used: rMEHFPGP, where r is glucuronic acid, KEHFPGP, GEHFPGP, EHFPGP, HFPGP, and ERP. The peptides were administered intraperitoneally at doses of 0.015, 0.05 and 0.5 mg/kg. Rat pain sensitivity was assessed using the paw-withdrawal test. Truncations of the N-terminal residues eliminated the analgesic activity. The peptide analgesic effect was observed after the replacement of the N-terminal methionine with lysine or after the attachment of glucuronic acid to the methionine, while the peptide with glycine instead of the methionine had no effect on pain sensitivity. Hence, the amino acid at position 1 of semax analogs plays a key role in mediating the analgesic effects of the peptides.
促黑素皮质素是促肾上腺皮质激素（ACTH）和促黑素（MSH）家族的肽类，具有广泛的生理活性。七肽司美格鲁肽（MEHFPGP）是ACTH4 - 10片段的类似物。此前，已证明该肽具有显著的益智和神经保护活性；此外，它还能降低动物的痛觉敏感性。在这项研究中，研究了该肽的镇痛活性与其结构之间的关系。使用了以下N端ACTH片段的类似物：rMEHFPGP（其中r为葡萄糖醛酸）、KEHFPGP、GEHFPGP、EHFPGP、HFPGP和ERP。这些肽以0.015、0.05和0.5 mg/kg的剂量腹腔注射。使用足趾退缩试验评估大鼠的痛觉敏感性。N端残基的截断消除了镇痛活性。用赖氨酸取代N端甲硫氨酸或在甲硫氨酸上连接葡萄糖醛酸后观察到肽的镇痛作用，而用甘氨酸取代甲硫氨酸的肽对痛觉敏感性没有影响。因此，司美格鲁肽类似物第1位的氨基酸在介导肽的镇痛作用中起关键作用。
