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Depth-Profiling the Nuclease Stability and the Gene Silencing Efficacy of Brush-Architectured Poly(ethylene glycol)–DNA Conjugates
- Source :
- J Am Chem Soc
- Publication Year :
- 2017
- Publisher :
- American Chemical Society (ACS), 2017.
-
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” towards 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.
- Subjects :
- Biodistribution
Surface Properties
02 engineering and technology
010402 general chemistry
01 natural sciences
Biochemistry
Article
Catalysis
Polyethylene Glycols
chemistry.chemical_compound
Colloid and Surface Chemistry
Enzyme Stability
Nucleotide
Gene Silencing
chemistry.chemical_classification
Nuclease
Deoxyribonucleases
biology
Nucleotides
Oligonucleotide
Chemistry
Nucleic Acid Strand
DNA
General Chemistry
021001 nanoscience & nanotechnology
0104 chemical sciences
biology.protein
Biophysics
Nucleic acid
PEGylation
Biological Assay
0210 nano-technology
Subjects
Details
- ISSN :
- 15205126 and 00027863
- Volume :
- 139
- Database :
- OpenAIRE
- Journal :
- Journal of the American Chemical Society
- Accession number :
- edsair.doi.dedup.....e0a56bb293adabe22b7be1ce0c0a1dd6