Lu Y A, Felix A M
Peptide Research Department, Roche Research Center, Hoffmann-La Roche Inc., Nutley, NJ 07110.
Pept Res. 1993 May-Jun;6(3):140-6.
The feasibility of pegylating peptides by the solid-phase procedure was examined. Although polyethyleneglycol (PEG) was shown to be partially degraded by HF, the use of TFA was fully compatible with the PEG system. Therefore, the Fmoc/tBu solid-phase strategy was utilized for the synthesis of a series of model tetra-, octa- and dodecapeptides, and the corresponding N alpha-pegylated peptides, which were prepared from common peptide-resin intermediates. PEG-OCH2-CO-Nle-OH, 3, proved to be an ideal reagent for N-terminal pegylation. This intermediate served as a diagnostic for the determination of the number of PEG units/mole of peptide. Solid-phase coupling reactions proceeded by standard procedures using BOP-activation. The authentic pegylated peptides (readily purified by conventional methods of preparative HPLC) were fully characterized by amino acid analysis, 1H-NMR spectroscopy, analytical HPLC and laser desorption ionization mass spectrometry, leading to the values that are identical with the expected structures.
研究了通过固相法对肽进行聚乙二醇化的可行性。尽管聚乙二醇（PEG）被证明会被HF部分降解，但TFA的使用与PEG系统完全兼容。因此，采用Fmoc/tBu固相策略合成了一系列模型四肽、八肽和十二肽，以及由常见肽树脂中间体制备的相应Nα-聚乙二醇化肽。PEG-OCH2-CO-Nle-OH（3）被证明是用于N端聚乙二醇化的理想试剂。该中间体可作为确定每摩尔肽中PEG单元数量的诊断试剂。固相偶联反应通过使用BOP活化的标准程序进行。通过氨基酸分析、1H-NMR光谱、分析型HPLC和激光解吸电离质谱对经常规制备型HPLC方法易于纯化的真实聚乙二醇化肽进行了全面表征，得到的值与预期结构一致。
