Stüber W, Kosina H, Heimburger N
Research Laboratories of Behringwerke AG, Marburg, Federal Republic of Germany.
Int J Pept Protein Res. 1988 Jan;31(1):63-70. doi: 10.1111/j.1399-3011.1988.tb00007.x.
The synthesis of the tripeptide D-Phe-Pro-Arg with the nitrile group instead of the carboxylgroup is described. Initially, the corresponding peptide amide was synthesized by conventional methods in solution using Boc and Fmoc as the protecting group for D-Phe. The dehydration in order to create the nitrile moiety was achieved by treating the peptide amide with phosphorus oxichloride or trifluoroacetic anhydride. Best results were obtained by the use of phosphorus oxichloride in pyridine as the solvent in the presence of imidazole. After deprotection of the N-terminal amino acid the crude product was purified by chromatography on Butyl-Fractogel HW-40 (S). The purity of the final product was checked on a RP18 phase by hplc. The existence of the nitrile group was demonstrated by i.r. and 13C-n.m.r. spectra. The peptide nitrile exhibited a strong inhibition of thrombin compared to the tripeptide amide.
描述了具有腈基而非羧基的三肽D-苯丙氨酸-脯氨酸-精氨酸的合成。最初，使用Boc和Fmoc作为D-苯丙氨酸的保护基团，通过常规溶液法合成了相应的肽酰胺。通过用三氯氧磷或三氟乙酸酐处理肽酰胺来实现脱水以形成腈部分。在咪唑存在下，以吡啶为溶剂使用三氯氧磷可获得最佳结果。在对N端氨基酸进行脱保护后，粗产物通过在丁基-弗拉克托凝胶HW-40(S)上进行色谱纯化。通过hplc在RP18相上检查最终产物的纯度。通过红外光谱和13C核磁共振光谱证明了腈基的存在。与三肽酰胺相比，该肽腈对凝血酶表现出强烈的抑制作用。
