Moroder L, Gemeiner M, Göhring W, Jaeger E, Musiol J, Scharf R, Stocker H, Wünsch E, Pradayrol L, Vaysse N, Ribet A
Hoppe Seylers Z Physiol Chem. 1981 Jun;362(6):697-716.
The total synthesis of the octacosapeptide corresponding to the proposed primary structure of porcine somatostatin-28 is described. The synthesis has been performed using a protection scheme of maximum selectivity (acid labile side chain protection based on tert-butyl alcohol and 1-adamantol derived protecting groups in combination with the S-tert-butylthio group for reversible and selective blocking of the cysteine thiol functions and the 2-nitrophenylthio group for the temporary protection of the alpha-amino functions of intermediate segments) and of carefully selected fragments. Upon assembly in sequence order of the four suitably protected fragments related to sequences 18-28, 15-17, 8-14 and 1-7, the asymmetric disulfides were reduced by exposure of the fully protected octacosapeptide to phosphines. Subsequently, the final deprotection was performed with trifluoroacetic acid and the resulting dihydrosomatostatin-28 was then converted by air oxidation into the "cyclic peptide". Gel filtration on Biogel P-6 and ion-exchange chromatography on Biogel CM-2 produced somatostatin-28 at a high degree of purity. Comparative analysis of the synthetic and natural product by means of chromatographic, immunological and biological assays confirmed the structure proposed for this putative precursor of somatostatin-14.
本文描述了与猪生长抑素-28推测的一级结构相对应的二十八肽的全合成。合成过程采用了具有最大选择性的保护策略（基于叔丁醇和1-金刚烷醇衍生的保护基团对酸不稳定的侧链进行保护，同时结合S-叔丁基硫醇基团对半胱氨酸硫醇功能进行可逆和选择性阻断，以及2-硝基苯硫醇基团对中间片段的α-氨基功能进行临时保护），并使用了精心挑选的片段。将与序列18-28、15-17、8-14和1-7相关的四个适当保护的片段按顺序组装后，通过将完全保护的二十八肽暴露于膦来还原不对称二硫键。随后，用三氟乙酸进行最终脱保护，然后通过空气氧化将所得的二氢生长抑素-28转化为“环肽”。在Biogel P-6上进行凝胶过滤和在Biogel CM-2上进行离子交换色谱，得到了高纯度的生长抑素-28。通过色谱、免疫和生物学分析对合成产物和天然产物进行比较分析，证实了为这种推测的生长抑素-14前体所提出的结构。
