THE SYNTHESIS OF OXYTOCIN
THE SYNTHESIS OF OXYTOCIN
复制标题
DOI：
10.1021/ja01641a004
复制
发表时间：
1954-01-01
影响因子：
15
通讯作者：
KATSOYANNIS, PG
中科院分区：
文献类型：
--
作者：
DUVIGNEAUD, V;RESSLER, C;KATSOYANNIS, PG
通过N-苄氧羰基-S-苄基-L-半胱氨酰-L-酪氨酸和七肽酰胺L-异亮氨酰-l-氨酰-L-天冬酰胺酰-S-苄基-l-半胱氨酰-L-脯氨酰-L-亮氨酰甘氨酰胺（IVa）的缩合，得到受保护的九肽酰胺VI，然后在液氨中用钠还原，并氧化所得的巯基九肽，合成了具有催产素激素活性的环状八肽酰胺（I）。IVa是由S-苄基-L-半胱氨酰-L-脯氨酰-L-亮氨酰甘氨酰胺与对甲苯磺酰-L-异亮氨酰-L-天冬酰胺缩合，除去缩合产物中的对甲苯磺酰基而制得。由此获得的生物活性合成材料已通过逆流分配纯化，并与天然催产素的效力、比旋光度、分配系数、氨基酸组成、电泳迁移率、红外图谱、分子量、酶和酸失活以及在树脂IRC-50上的层析进行比较。还比较了合成材料和天然催产素在人和大鼠离体子宫收缩中的排乳和引产作用。用合成材料和天然催产素制备的结晶黄酸酯具有相同的晶型、熔点和混合熔点。所有这些比较为合成产物与天然催产素的同一性提供了令人信服的证据。因此，这种合成构成了多肽激素的第一次合成。
A cyclic octapeptide amide (I) having the hormonal activity of oxytocin has been synthesized through the condensation of N-carbobenzoxy-S-benzyl-L-cysteinyl-L-tyrosine and the heptapeptide amide L-isoleucyl-L-glutaminyl-L-asparaginyl-S-benzyl-L-cysteinyl-L-prolyl-L-leucylglycinamide (IVa) to yield the protected nonapeptide amide VI followed by reduction with sodium in liquid ammonia and oxidation of the resulting sulfhydryl nonapeptide. IVa was prepared by the condensa-tion of S-benzyl-L-cysteinyl-L-prolyl-L-leucylglycinamide with tosyl-L-isoleucyl-L-glutaminyl-L-asparagine followed by re-moval of the tosyl group from the condensation product. The biologically active synthetic material thus obtained has been purified by countercurrent distribution and compared with natural oxytocin as to potency, specific rotation, partition coefficients, amino acid composition, electrophoretic mobility, infrared pattern, molecular weight, enzymatic and acid inactivation and chromatography on the resin IRC-50. The synthetic material and natural oxytocin were also compared with respect to milk ejection and induction of labor in the human as well as rat uterus contraction in vitro. The crystalline flavi-anates prepared from the synthetic material and from natural oxytocin were found to have the same crystalline form, melting point and mixedmelting point. All of these comparisons affordedconvincing evidence of the identity of the synthetic prod-uct with natural oxytocin. This synthesis thus constitutes the first synthesis of a polypeptide hormone.