Department of Materials Engineering, Graduate School of Engineering, and Center for NanoBio Integration, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
Bioconjug Chem. 2010 Feb 17;21(2):248-54. doi: 10.1021/bc900253p.
Versatile route for "click chemistry" compatible heterobifunctional PEGs was established through preparation of alpha-tetrahydropyranyloxy-omega-hydroxyl poly(ethylene glycol) (THP-PEG-OH) via ring-opening polymerization of ethylene oxide using 2-(tetrahydro-2H-pyran-2-yloxy)ethanol as an initiator, followed by the functionalization of omega-OH group to either the azido or alkyne group. Quantitative azidation of THP-PEG-OH was confirmed from the analysis of molecular functionality of the derivatives. While the conversion efficiency of omega-alkynation was appropriately 70%, the unreacted THP-PEG-OH fraction was successfully removed by ion-exchange chromatography after the carboxylation of the hydroxyl group with succinic anhydride. Then, the protecting group of the alpha-end, THP, was removed in mild acidic media, followed by two- or three-step modification of the resulting alpha-hydroxyl group to primary amino or thiol groups. Consequently, "click chemistry" compatible heterobifunctional PEG derivatives (X-PEG-Y; X = NH(2) and SH, Y =Azide and Alkyne) were synthesized with high efficiency and controlled molecular weight.
建立了一种通过使用 2-（四氢-2H-吡喃-2-基氧基）乙醇作为引发剂开环聚合环氧乙烷来制备α-四氢吡喃氧基-ω-羟基聚（乙二醇）（THP-PEG-OH）的方法，该方法适用于“点击化学”兼容的杂双功能 PEG。然后，通过将羟基与琥珀酸酐进行羧化反应，将 ω-OH 基团官能化至叠氮化物或炔基。THP-PEG-OH 的定量叠氮化反应从衍生物的分子官能度分析中得到证实。虽然 ω-炔基化的转化率适当为 70％，但在羟基用琥珀酸酐进行羧化后，通过离子交换色谱法可以成功地除去未反应的 THP-PEG-OH 部分。然后，在温和的酸性介质中除去α-末端的保护基团 THP，然后再对所得的α-羟基进行两步或三步修饰以得到伯氨基或巯基。因此，高效且可控分子量地合成了“点击化学”兼容的杂双功能 PEG 衍生物（X-PEG-Y；X = NH 2 和 SH，Y = 叠氮化物和炔基）。
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