Roy U, Gazis D, Dal Pan G, Schwartz I L, Roy J
Int J Pept Protein Res. 1983 Nov;22(5):525-38. doi: 10.1111/j.1399-3011.1983.tb02125.x.
In an attempt to see whether the C=O and the NH2 of CONH2 of asparagine5 and glycinamide9 are both essential for biological activity, [5-beta-cyanoalanine] oxytocin and [9-alpha-aminoacetonitrile] oxytocin have been synthesized. Each of these analogs contains a nitrile group in place of the carboxamide group of Asn5 and GlyNH92 respectively; the nitrile group can simulate the carbonyl portion of the carboxamide, but lacks the hydrogen-bond donating capacity of its NH2 portion. Substitution of a nitrile group produced opposite biological effects in the 5 and the 9 positions; the 5-substituted analog showed very low activities (less than 3% of those of oxytocin) while the 9-substituted analog showed extremely high activities (with an in vivo uterine activity of 906 U/mg almost twice that of oxytocin). The results clearly suggest that the mechanisms of interaction of the carboxamide groups with the receptor sites are different for residues 5 and 9.
为了探究天冬酰胺5的C=O和CONH2的NH2以及甘氨酰胺9是否对生物活性均至关重要，已合成了[5-β-氰基丙氨酸]催产素和[9-α-氨基乙腈]催产素。这些类似物中的每一个分别含有一个腈基，以取代Asn5和GlyNH92的羧酰胺基团；腈基可以模拟羧酰胺的羰基部分，但缺乏其NH2部分的氢键供体能力。腈基取代在5位和9位产生了相反的生物学效应；5-取代类似物显示出非常低的活性（低于催产素活性的3%），而9-取代类似物显示出极高的活性（体内子宫活性为906 U/mg，几乎是催产素的两倍）。结果清楚地表明，羧酰胺基团与受体位点相互作用的机制对于残基5和9是不同的。
