Thymosin .alpha.1 and other peptide amides are synthesized in the solid phase using methylbenzhydrylamine resin as the support and hydrogen bromide as the deprotecting and cleaving agents. The N-terminal 14 amino acid partial sequence of thymosin .alpha.1, Ac-Ser-Asp-Ala-Ala-Val-Asp-Thr-Ser-Ser-Glu-Ile-Thr-Thr-Lys-OH is synthesized on benzyl ester resin. Using a mixture of hydrogen bromide, anisole and thioanisole as the cleavage and deprotection composition, the yields of the cleaved peptide and the selectivity of the deprotection is highly improved. For example, yields of thymosin .alpha.1 have been increased by about 90% as compared to the use of hydrogen bromide alone. By using hydrogen bromide rather than hydrogen fluoride, the synthesis can use conventional laboratory glassware and the synthesis can be easily scaled up to commercial production.
Thymosin .alpha.1和其他肽酰胺在固相合成中使用甲基苯甲酰胺
树脂作为支持和
氢溴酸作为去保护和裂解试剂。 Thymosin .alpha.1的N末端14个
氨基酸部分序列Ac-Ser-Asp-Ala-Ala-Val-Asp-Thr-Ser-Ser-Glu-Ile-Thr-Thr-Lys-OH在苄酯
树脂上合成。使用
氢溴酸,
苯甲醚和
硫代苯醚混合物作为裂解和去保护组合物,裂解肽的产率和去保护的选择性得到了极大的改善。例如,与仅使用
氢溴酸相比,Thymosin .alpha.1的产率提高了约90%。通过使用
氢溴酸而不是
氢氟酸,合成可以使用传统的实验室
玻璃器皿,并且可以轻松扩大到商业生产规模。