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双降解响应性自组装多价树状大分子 - 树突与 DNA 之间的临时纳米级识别。

Double-degradable responsive self-assembled multivalent arrays--temporary nanoscale recognition between dendrons and DNA.

机构信息

Department of Chemistry, University of York, Heslington, York YO10 5DD, UK.

出版信息

Org Biomol Chem. 2014 Jan 21;12(3):446-55. doi: 10.1039/c3ob42202j. Epub 2013 Nov 22.

Abstract

This article reports self-assembling dendrons which bind DNA in a multivalent manner. The molecular design directly impacts on self-assembly which subsequently controls the way these multivalent nanostructures bind DNA--this can be simulated by multiscale modelling. Incorporation of an S-S linkage between the multivalent hydrophilic dendron and the hydrophobic units responsible for self-assembly allows these structures to undergo triggered reductive cleavage, with dithiothreitol (DTT) inducing controlled breakdown, enabling the release of bound DNA. As such, the high-affinity self-assembled multivalent binding is temporary. Furthermore, because the multivalent dendrons are constructed from esters, a second slow degradation step causes further breakdown of these structures. This two-step double-degradation mechanism converts a large self-assembling unit with high affinity for DNA into small units with no measurable binding affinity--demonstrating the advantage of self-assembled multivalency (SAMul) in achieving highly responsive nanoscale binding of biological targets.

摘要

本文报道了通过多价方式结合 DNA 的自组装树状大分子。分子设计直接影响自组装,进而控制这些多价纳米结构与 DNA 结合的方式——这可以通过多尺度建模进行模拟。在多价亲水树状大分子和负责自组装的疏水性单元之间引入 S-S 键合,允许这些结构进行触发还原裂解,二硫苏糖醇 (DTT) 诱导可控断裂,从而释放结合的 DNA。因此,高亲和力的自组装多价结合是暂时的。此外,由于多价树状大分子由酯构成,第二个缓慢的降解步骤会导致这些结构进一步分解。这种两步双重降解机制将具有高 DNA亲和力的大自组装单元转化为没有可测量结合亲和力的小单元——证明了自组装多价性 (SAMul) 在实现生物靶标高度响应性纳米级结合方面的优势。

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