Peptides displayed as high density brush polymers resist proteolysis and retain bioactivity.
Peptides displayed as high density brush polymers resist proteolysis and retain bioactivity.
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肽显示为高密度刷聚合物抗蛋白水解并保留生物活性。
DOI：
10.1021/ja5088216
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发表时间：
2014-10-29
影响因子：
15
通讯作者：
Gianneschi, Nathan C.
中科院分区：
文献类型：
--
作者：
Blum, Angela P.;Kammeyer, Jacquelin K.;Yin, Jian;Crystal, Dustin T.;Rush, Anthony M.;Gilson, Michael K.;Gianneschi, Nathan C.
我们描述了一种策略，使肽抗蛋白水解，制定高密度刷聚合物。这种方法的实用性是通过聚合良好建立的细胞穿透肽（CPP），并显示所得的聚合物不仅耐蛋白水解，但也保持其进入细胞的能力。通过研究由作为凝血酶或金属蛋白酶底物的肽组成的刷状聚合物的抗蛋白水解性来探索这种设计概念的范围。最后，我们证明了肽刷聚合物的蛋白水解敏感性可以通过调整聚合物刷的密度来调整，并提供计算机模型来合理化这一发现。我们认为，这种策略提供了一个合理的方法，在体内使用的肽，蛋白酶的快速消化传统上限制了他们的效用。
We describe a strategy for rendering peptides resistant to proteolysis by formulating them as high-density brush polymers. The utility of this approach is demonstrated by polymerizing well-established cell-penetrating peptides (CPPs) and showing that the resulting polymers are not only resistant to proteolysis but also maintain their ability to enter cells. The scope of this design concept is explored by studying the proteolytic resistance of brush polymers composed of peptides that are substrates for either thrombin or a metalloprotease. Finally, we demonstrate that the proteolytic susceptibility of peptide brush polymers can be tuned by adjusting the density of the polymer brush and offer in silico models to rationalize this finding. We contend that this strategy offers a plausible method of preparing peptides for in vivo use, where rapid digestion by proteases has traditionally restricted their utility.
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影响因子：
29.4
作者：
Chien, Miao-Ping;Thompson, Matthew P.;Barback, Christopher V.;Ku, Ti-Hsuan;Hall, David J.;Gianneschi, Nathan C.
通讯作者：
Gianneschi, Nathan C.
DOI：
10.1016/j.jconrel.2011.10.016
发表时间：
2012-02-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Chu DS;Johnson RN;Pun SH
通讯作者：
Pun SH
影响因子：
7.3
作者：
Heitz F;Morris MC;Divita G
通讯作者：
Divita G
影响因子：
15
作者：
James, Carrie R.;Rush, Anthony M.;Gianneschi, Nathan C.
通讯作者：
Gianneschi, Nathan C.
影响因子：
3.5
作者：
Belitsky, JM;Leslie, SJ;Dervan, PB
通讯作者：
Dervan, PB