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J Am Chem Soc. 2017 Aug 9;139(31):10605-10608. doi: 10.1021/jacs.7b05064. Epub 2017 Jul 26.

Depth-Profiling the Nuclease Stability and the Gene Silencing Efficacy of Brush-Architectured Poly(ethylene glycol)-DNA Conjugates.

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1
Department of Chemistry and Chemical Biology, Northeastern University , Boston, Massachusetts 02115, United States.

Abstract

PEGylation of an oligonucleotide using a brush polymer can improve its biopharmaceutical characteristics, including enzymatic stability and biodistribution. Herein, we quantitatively explore the nuclease accessibility of the nucleic acid as a function of "depth" toward the backbone of the brush polymer. It is found that protein accessibility decreases as the nucleotide is located closer to the backbone. Thus, by moving the conjugation point from the terminus of the nucleic acid strand to an internal position, much smaller brushes can be used to achieve the same level of steric shielding. This finding also makes it possible to assess antisense gene regulation efficiency of these brush-DNA conjugates as a function of their nuclease stability.

PMID:
28737410
DOI:
10.1021/jacs.7b05064
[Indexed for MEDLINE]

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