Stüber W, Knolle J, Breipohl G
Research Laboratories of Behringwerke AG, Marburg, Federal Republic of Germany.
Int J Pept Protein Res. 1989 Sep;34(3):215-21. doi: 10.1111/j.1399-3011.1989.tb00233.x.
The preparation and use of new anchor groups for the synthesis of peptide amides by solid-phase peptide synthesis employing the Fmoc-method is described. Based on the structure of the 4,4'-dimethoxybenzhydryl group (Mbh) handles were developed, which could be cleaved by mild acid treatment to give carboxamides. The syntheses and application of Fmoc-amino-acid-(4-carboxylatomethyloxyphenyl-4'-methoxyphenyl) methyl amide and Fmoc-(4-carboxylatopropyloxyphenyl-4'-methoxyphenyl) methyl amide are described in detail. These handles were coupled to resins and a stepwise elongation of peptide chains proceeded smoothly with N alpha-9-fluorenylmethoxycarbonyl (Fmoc) amino acid derivatives using a carbodiimide/HOBt mediated reaction. The final cleavage of side-chain protecting groups and the release of the C-terminal amide moiety was achieved by the treatment with trifluoroacetic acid, dichloromethane in the presence of scavengers. Various peptides, such as the Leu-enkephalin amide and Leu-Gly-Gly-Gly-Gln-Gly-Lys-Val-Leu-Gly-NH2, which is a good substrate for F XIII, were prepared in high yields and purities.
描述了通过采用Fmoc方法的固相肽合成制备和使用新的锚定基团来合成肽酰胺。基于4,4'-二甲氧基二苯甲基（Mbh）的结构开发了处理方法，其可通过温和的酸处理裂解得到羧酰胺。详细描述了Fmoc-氨基酸-（4-羧基甲基氧基苯基-4'-甲氧基苯基）甲基酰胺和Fmoc-（4-羧基丙氧基苯基-4'-甲氧基苯基）甲基酰胺的合成及应用。这些处理方法与树脂偶联，使用碳二亚胺/HOBt介导的反应，肽链与Nα-9-芴甲氧羰基（Fmoc）氨基酸衍生物逐步顺利延长。通过在清除剂存在下用三氟乙酸、二氯甲烷处理实现侧链保护基团的最终裂解和C端酰胺部分的释放。以高产率和高纯度制备了各种肽，如亮脑啡肽酰胺和Leu-Gly-Gly-Gly-Gln-Gly-Lys-Val-Leu-Gly-NH2（它是F XIII的良好底物）。
