Nawrocka-Bolewska E, Kubik A, Szewczuk Z, Siemion I Z, Obuchowicz E, Gołba K, Herman Z S
Institute of Chemistry, Wrocław University, Poland.
Pol J Pharmacol Pharm. 1991 Jul-Aug;43(4):281-8.
C-Terminal dipeptide fragment of tuftsin, Pro-Arg, substituted by D-amino acids, and tuftsin analogs with n-hexyl- and n-heptylamine coupled to their C-termini were synthesized by a classical method in solution and their antinociceptive activity was measured by tail flick immersion test (0.4 microM/icv). D-Pro-D-Arg and D-Pro-L-Arg showed an analgesic activity, with the duration of 60 and 40 min, respectively. The strong behavioral effects observed after injection of D-Pro-D-Arg were decreased by naloxone. L-Pro-D-Arg and Thr-Lys-Pro-Arg-HxA display no antinociceptive effect; the tetrapeptide amide showed some toxicity effects. Thr-Lys-Pro-Arg-HpA was very toxic and caused death of all experimental animals. This effect was not influenced by previous injection of naloxone.
合成了用D-氨基酸取代的促吞噬肽C末端二肽片段Pro-Arg，以及C末端偶联正己胺和正庚胺的促吞噬肽类似物，采用经典的溶液法合成，并通过甩尾浸没法（0.4微摩尔/脑室内注射）测定其抗伤害感受活性。D-脯氨酸-D-精氨酸和D-脯氨酸-L-精氨酸显示出镇痛活性，持续时间分别为60分钟和40分钟。注射D-脯氨酸-D-精氨酸后观察到的强烈行为效应被纳洛酮减弱。L-脯氨酸-D-精氨酸和苏氨酸-赖氨酸-脯氨酸-精氨酸-己胺没有抗伤害感受作用；四肽酰胺显示出一些毒性作用。苏氨酸-赖氨酸-脯氨酸-精氨酸-庚胺毒性很强，导致所有实验动物死亡。这种效应不受先前注射纳洛酮的影响。
