基于底物的细胞穿透聚二硫键的合成。
Substrate-initiated synthesis of cell-penetrating poly(disulfide)s.
机构信息
School of Chemistry and Biochemistry, University of Geneva, Geneva, Switzerland.
出版信息
J Am Chem Soc. 2013 Feb 13;135(6):2088-2091. doi: 10.1021/ja311961k. Epub 2013 Feb 4.
Abstract
Lessons from surface-initiated polymerization are applied to grow cell-penetrating poly(disulfide)s directly on substrates of free choice. Reductive depolymerization after cellular uptake should then release the native substrates and minimize toxicity. In the presence of thiolated substrates, propagators containing a strained disulfide from asparagusic or, preferably, lipoic acid and a guanidinium cation polymerize into poly(disulfide)s in less than 5 min at room temperature at pH 7. Substrate-initiated polymerization of cationic poly(disulfide)s and their depolymerization with dithiothreitol causes the appearance and disappearance of transport activity in fluorogenic vesicles. The same process is further characterized by gel-permeation chromatography and fluorescence resonance energy transfer.
摘要
受表面引发聚合的启发，人们直接在各种自由选择的基底上生长穿膜聚（二硫键）。细胞摄取后，通过还原解聚，应该可以释放出原始的基底并将毒性降至最低。在巯基化底物存在的情况下，含有来自天门冬氨酸或更优选的脂环酸的张力二硫键和胍阳离子的引发剂在室温 pH 值为 7 下少于 5 分钟即可聚合形成聚（二硫键）。阳离子聚（二硫键）的底物引发聚合及其与二硫苏糖醇的解聚导致荧光囊泡中转运活性的出现和消失。同样的过程还可以通过凝胶渗透色谱法和荧光共振能量转移来进一步表征。
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