Department of Chemistry, University of Oxford, Oxford, UK.
Kyoto Pharmaceutical University, Kyoto, Japan.
Nat Nanotechnol. 2019 Dec;14(12):1135-1142. doi: 10.1038/s41565-019-0579-7. Epub 2019 Nov 18.
Chemists have long sought the ability to modify molecules precisely when presented with several sites of similar reactivity. We reasoned that the confinement of substrates within nanostructures might permit site-selective reactions unachievable in bulk solution, even with sophisticated reagents. In particular, the stretching and alignment of polymers within nanotubes might allow site-specific cleavage or modification. To explore this proposition, macromolecular disulfide substrates were elongated within members of a collection of tubular protein nanoreactors, which contained cysteine residues positioned at different locations along the length of each tube. For each nanoreactor, we defined the reactive location by using a set of polymer substrates (site-selectivity) and which of the two sulfur atoms was attacked (regioselectivity), and found that disulfide interchange occurs with atomic precision. Our strategy has potential for the selective processing of a wide variety of biomacromolecules, and the chemistry and substrates might be generalized yet further by using alternative nanotubes.
化学家们长期以来一直希望能够在多个具有相似反应活性的位点上精确地修饰分子。我们推断，将底物限制在纳米结构内可能允许在本体溶液中无法实现的选择性反应，即使使用复杂的试剂也是如此。特别是，聚合物在纳米管内的拉伸和排列可能允许进行特定位置的切割或修饰。为了探索这一假设，大分子二硫键底物在一组管状蛋白纳米反应器的成员中伸长，其中包含半胱氨酸残基，它们位于每个管的不同位置。对于每个纳米反应器，我们通过使用一组聚合物底物（选择性）和两个硫原子中的哪一个被攻击（区域选择性）来定义反应位置，并发现二硫键交换具有原子精度。我们的策略有可能对各种生物大分子进行选择性加工，并且通过使用替代的纳米管，化学和底物可能会进一步推广。
