大鼠心房肽Ⅲ及其小分子类似物的合成与生物活性

以逐步合成法固相合成了大鼠心房肽Ⅲ(APⅢ)及22肽的小分子类似物。用无水氟化氢将肽从树脂上切下,同时脱除所有侧链保护基。还原产物在30%乙酸高度稀释下用碘作氧化剂,使分子内2个半胱氨酸氧化形成二硫键。经SephadexG-l5柱层析、透析和高效液相层析分离纯化,获得在反相高效液相层析(分析柱)为单一峰的高纯度产物。酸水解后氨基酸组成分析证实与理论值相符,生物活性测定表明,合成的APⅢ有强利尿、利尿钠、降血压和舒张血管乎滑肌作用。化学修饰后的小分子APⅢ类似物有APⅢ的全部生物活性,且作用时间延长。

SYNTHESIS AND BIOLOGICAL ACTIVITY OF ATRIOPEPTIN Ⅲ AND ITS SMALL MOLECULAR ANALOG

Atriopeptin Ⅲ(AP Ⅲ)and its small molecular analog were synthesizedmanually by stepwise solid-phase method. The peptides were oxidized with iodine in 30%acetic acid at very high dilution to form intramolecular disulfide bridge and purified tohomogeneity by conventional means, including Sephadex G15,dialysis and reversed-phaseHPLC. Bioassay study demonstrated that the synthetic AP Ⅲpossesses potent bioactivitiesidenticaI to those of the same product of Peninsula Lab both in vitro and in vivo;whereas thelinear peptide,having the same primary structure as AP Ⅲ,showed very limitedbioactivity. The small analog, with Ser-Ser-residue deleted from the N-terminal of AP Ⅲ.was equipotent as AP Ⅲ while exhibiting a longer half-life in vivo resulting from the peptidemodification.