期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 136, 期 43, 页码 15422-15437出版社
AMER CHEMICAL SOC
DOI: 10.1021/ja5088216
关键词
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资金
- AFOSR through PECASE [FA9550-11-1-0105]
- BRI grant [FA99550-12-1-0414]
- NIH [1DP2OD008724]
- NIH through NIBIB [1R01EB011633]
- ARO [W911NF-14-1-0169]
- American Cancer Society - North Texans Creating Tomorrow's Miracles Postdoctoral Fellowship
- CRIN program, UCSD
- UCSD Light Microscopy Facility (P30 Grant) [NS047101]
- [NHLBI R01HL117326]
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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