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脱氧催产素是一种异二元环状肽，是肽激素催产素的合成类似物，具有延长的活性。

Demoxytocin, a heterodetic cyclic peptide, is the synthetic analog of the peptide hormone oxytocin with prolonged activity.

二硫键广泛存在与蛋白结构中，对稳定蛋白结构具有非常重要的意义，二硫键一般是通过序列中的2个Cys的巯基，经氧化形成。
 

形成二硫键的方法很多：空气氧化法，DMSO氧化法，过氧化氢氧化法等。
 

二硫键的合成过程，  可以通过Ellman检测以及HPLC检测方法对其反应进程进行监测。  
   

如果多肽中只含有1对Cys，那二硫键的形成是简单的。多肽经固相或液相合成，然后在pH8-9的溶液中进行氧化。      
 

当需要形成2对或2对以上的二硫键时，合成过程则相对复杂。尽管二硫键的形成通常是在合成方案的最后阶段完成，但有时引入预先形成的二硫化物是有利于连合或延长肽链的。通常采用的巯基保护基有trt, Acm, Mmt, tBu, Bzl, Mob, Tmob等多种基团。我们分别列出两种以2-Cl树脂和Rink树脂为载体合成的多肽上多对二硫键形成路线：
 

二硫键反应条件选择    
 

 二硫键即为蛋白质或多肽分子中两个不同位点Cys的巯基（-SH）被氧化形成的S-S共价键。 一条肽链上不同位置的氨基酸之间形成的二硫键，可以将肽链折叠成特定的空间结构。多肽分 子通常分子量较大，空间结构复杂，结构中形成二硫键时要求两个半胱氨酸在空间距离上接近。 此外，多肽结构中还原态的巯基化学性质活泼，容易发生其他的副反应，而且肽链上其他侧链 也可能会发生一系列修饰，因此，肽链进行修饰所选取的氧化剂和氧化条件是反应的关键因素， 反应机理也比较复杂，既可能是自由基反应，也可能是离子反应。      

反应条件有多种选择，比如空气氧化，DMSO氧化等温和的氧化过程，也可以采用H2O2，I2， 汞盐等激烈的反应条件。
 

空气氧化法： 空气氧化法形成二硫键是多肽合成中最经典的方法，通常是将巯基处于还原态的多肽溶于水中，在近中性或弱碱性条件下（PH值6.5-10），反应24小时以上。为了降低分子之间二硫键形成的可能，该方法通常需要在低浓度条件下进行。
 

碘氧化法：将多肽溶于25%的甲醇水溶液或30%的醋酸水溶液中，逐滴滴加10-15mol/L的碘进行氧化，反应15-40min。当肽链中含有对碘比较敏感的Tyr、Trp、Met和His的残基时，氧化条件要控制的更精确，氧化完后，立即加入维生素C或硫代硫酸钠除去过量的碘。 当序列中有两对或多对二硫键需要成环时，通常有两种情况：
 

自然随机成环:       序列中的Cys之间随机成环，与一对二硫键成环条件相似；
 

定点成环：       定点成环即序列中的Cys按照设计要求形成二硫键，反应过程相对复杂。在 固相合成多肽之前，需要提前设计几对二硫键形成的顺序和方法路线，选择不同的侧链 巯基保护基，利用其性质差异，分步氧化形成两对或多对二硫键。       通常采用的巯基保护 基有trt, Acm, Mmt, tBu, Bzl, Mob, Tmob等多种基团。

1. Induction of labor and cervical ripening by intracervical prostaglandin E2

C Lenstrup, S S Sørensen, V Brocks Obstet Gynecol . 1985 Jan;65(1):110-4.

A randomized double-blind trial was conducted over 48 hours comparing the effectiveness of prostaglandin E2 gel administered intracervically with that of demoxytocin buccal tablets for induction of labor in 103 patients with unripe cervical status (Bishop score 5 or less). A statistically significant difference was found in success frequency between the two groups, both on the first day (54.7 and 34.0%, respectively) and on the second day (82.0 and 61.9%, respectively; P less than .05). Without being matched, variables influencing the course of labor in the two groups were comparable. There was no statistically significant difference in the induction-delivery interval between the two groups during the first and second days of the trial. In both the prostaglandin E2 and the demoxytocin groups, patients who had not gone into labor during the first day showed a statistically significant increment in the Bishop score on the morning of the second day (2.4 and 1.3, respectively; P less than .01). The frequency of instrumental deliveries and cesarean section was the same in both groups; neither hypertonic uterine contractions nor side effects were observed in any patient. It is concluded that prostaglandin E2 gel administered intracervically is particularly well suited for the induction of labor in patients with unripe cervical status because of its combined contraction-inducing and cervical-ripening properties.

2. A comparative study of labor induced by oral prostaglandin E2 and buccal tablets of demoxytocin

M Ulstein, S N Eikhom, N Sagen Int J Gynaecol Obstet . 1979 Nov-Dec;17(3):243-5. doi: 10.1002/j.1879-3479.1979.tb00158.x.

A comparative study of the efficacy of oral prostaglandin E2 and buccal tablets of demoxytocin for induction of labor in overdue pregnancies was made in groups of randomly selected patients. Labor was successfully induced in 95.7% of the women in the prostaglandin group and 92.1% of the women in the demoxytocin group. Although the operative delivery rate was low in both groups, it was significantly higher for the demoxytocin group. A low rate of perinatal distress was recorded and there were no serious side effects in either group. The time from start of induction until delivery, as well as the time from amniotomy until delivery, were compared for primiparae and multiparae separately. No significant differences were found. The blood loss during the third stage of labor was lower in the prostaglandin group. We find oral induction of labor in overdue pregnancies effective, safe and convenient.

3. Use of oral oxytocics for stimulation of labor in cases of premature rupture of the membranes at term. A randomized comparative study of prostaglandin E2 tablets and demoxytocin resoriblets

A P Lange, J G Westergaard, G T Pedersen, N J Secher Acta Obstet Gynecol Scand . 1983;62(2):111-6. doi: 10.3109/00016348309155773.

The efficacy of oral PGE2 tablets and buccal demoxytocin (resoriblets) for the induction of labor in cases of premature rupture of the membranes (PROM) after the 37th week of gestation has been evaluated in a prospective, randomized investigation of 193 women. PGE2 tablets (Prostin) were given to 109 parturients and demoxytocin resoriblets (Sandopart) to 84. The former were given in increasing doses from an initial 0.5 mg to a maximum of 1.5 mg every hour. The demoxytocin was administered at a constant dosage of 50 I.U. every 30 min. The treatment was unsuccessful in 10 of the women treated with PGE2 tablets and in 19 women receiving demoxytocin resoriblets. In addition, the treatment had to be discontinued in 5 women in the PGE2 group due to gastrointestinal side effects. This gives a total success rate of 86.3% for treatment with PGE2 against 77.4% in respect of demoxytocin. This difference is not significant. No difference was observed between the two treatment groups as regards: the stimulation-delivery interval, duration of the various stages of labor, efficacy in primiparae and multiparae, efficacy in patients with a high/low Bishop score. A significantly higher frequency of gastro-intestinal side effects was seen in those treated with PGE2 (21.7%) as compared with demoxytocin (3.6%). The frequency of surgical intervention was 17% in the PGE2 group and 10% in the demoxytocin group. In 4 cases where the stimulation was successful, cesarean section was carried out for reasons unrelated to the drug therapy. Despite the fact that demoxytocin treatment results in fewer side effects than PGE2, the efficacy of the drug is not superior. Based on experience from previous investigations carried out in this department, where intravenous oxytocin was found to be clearly better than oral PGE2 for the induction of labor in cases of PROM, intravenous oxytocin will remain the method of choice due to the shorter period of treatment, which must take priority.