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Title: DNA origami protection and molecular interfacing through engineered sequence-defined peptoids

Abstract

DNA nanotechnology has established approaches for designing programmable and precisely controlled nanoscale architectures through specific Watson−Crick base-pairing, molecular plasticity, and intermolecular connectivity. In particular, superior control over DNA origami structures could be beneficial for biomedical applications, including biosensing, in vivo imaging, and drug and gene delivery. However, protecting DNA origami structures in complex biological fluids while preserving their structural characteristics remains a major challenge for enabling these applications. Here, we developed a class of structurally well-defined peptoids to protect DNA origamis in ionic and bioactive conditions and systematically explored the effects of peptoid architecture and sequence dependency on DNA origami stability. The applicability of this approach for drug delivery, bioimaging, and cell targeting was also demonstrated. A series of peptoids (PE1–9) with two types of architectures, termed as “brush” and “block,” were built from positively charged monomers and neutral oligo-ethyleneoxy monomers, where certain designs were found to greatly enhance the stability of DNA origami. Through experimental and molecular dynamics studies, we demonstrated the role of sequence-dependent electrostatic interactions of peptoids with the DNA backbone. We showed that octahedral DNA origamis coated with peptoid (PE2) can be used as carriers for anticancer drug and protein, where the peptoid modulated the ratemore » of drug release and prolonged protein stability against proteolytic hydrolysis. Finally, we synthesized two alkyne-modified peptoids (PE8 and PE9), conjugated with fluorophore and antibody, to make stable DNA origamis with imaging and cell-targeting capabilities. Our results demonstrate an approach toward functional and physiologically stable DNA origami for biomedical applications.« less

Authors:
; ; ORCiD logo; ; ; ; ORCiD logo; ; ORCiD logo; ORCiD logo;
Publication Date:
Research Org.:
Brookhaven National Lab. (BNL), Upton, NY (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES)
OSTI Identifier:
1604260
Alternate Identifier(s):
OSTI ID: 1607714
Report Number(s):
BNL-213757-2020-JAAM
Journal ID: ISSN 0027-8424
Grant/Contract Number:  
SC0012704; AC02-05CH11231; SC0008772; KP1605010
Resource Type:
Published Article
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Volume: 117 Journal Issue: 12; Journal ID: ISSN 0027-8424
Publisher:
National Academy of Sciences
Country of Publication:
United States
Language:
English
Subject:
36 MATERIALS SCIENCE; DNA Nanotechnology; Peptoid; Molecular Coating

Citation Formats

Wang, Shih-Ting, Gray, Melissa A., Xuan, Sunting, Lin, Yiyang, Byrnes, James, Nguyen, Andy I., Todorova, Nevena, Stevens, Molly M., Bertozzi, Carolyn R., Zuckermann, Ronald N., and Gang, Oleg. DNA origami protection and molecular interfacing through engineered sequence-defined peptoids. United States: N. p., 2020. Web. doi:10.1073/pnas.1919749117.
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Wang, Shih-Ting, Gray, Melissa A., Xuan, Sunting, Lin, Yiyang, Byrnes, James, Nguyen, Andy I., Todorova, Nevena, Stevens, Molly M., Bertozzi, Carolyn R., Zuckermann, Ronald N., & Gang, Oleg. DNA origami protection and molecular interfacing through engineered sequence-defined peptoids. United States. https://doi.org/10.1073/pnas.1919749117
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Wang, Shih-Ting, Gray, Melissa A., Xuan, Sunting, Lin, Yiyang, Byrnes, James, Nguyen, Andy I., Todorova, Nevena, Stevens, Molly M., Bertozzi, Carolyn R., Zuckermann, Ronald N., and Gang, Oleg. Thu . "DNA origami protection and molecular interfacing through engineered sequence-defined peptoids". United States. https://doi.org/10.1073/pnas.1919749117.
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@article{osti_1604260,
title = {DNA origami protection and molecular interfacing through engineered sequence-defined peptoids},
author = {Wang, Shih-Ting and Gray, Melissa A. and Xuan, Sunting and Lin, Yiyang and Byrnes, James and Nguyen, Andy I. and Todorova, Nevena and Stevens, Molly M. and Bertozzi, Carolyn R. and Zuckermann, Ronald N. and Gang, Oleg},
abstractNote = {DNA nanotechnology has established approaches for designing programmable and precisely controlled nanoscale architectures through specific Watson−Crick base-pairing, molecular plasticity, and intermolecular connectivity. In particular, superior control over DNA origami structures could be beneficial for biomedical applications, including biosensing, in vivo imaging, and drug and gene delivery. However, protecting DNA origami structures in complex biological fluids while preserving their structural characteristics remains a major challenge for enabling these applications. Here, we developed a class of structurally well-defined peptoids to protect DNA origamis in ionic and bioactive conditions and systematically explored the effects of peptoid architecture and sequence dependency on DNA origami stability. The applicability of this approach for drug delivery, bioimaging, and cell targeting was also demonstrated. A series of peptoids (PE1–9) with two types of architectures, termed as “brush” and “block,” were built from positively charged monomers and neutral oligo-ethyleneoxy monomers, where certain designs were found to greatly enhance the stability of DNA origami. Through experimental and molecular dynamics studies, we demonstrated the role of sequence-dependent electrostatic interactions of peptoids with the DNA backbone. We showed that octahedral DNA origamis coated with peptoid (PE2) can be used as carriers for anticancer drug and protein, where the peptoid modulated the rate of drug release and prolonged protein stability against proteolytic hydrolysis. Finally, we synthesized two alkyne-modified peptoids (PE8 and PE9), conjugated with fluorophore and antibody, to make stable DNA origamis with imaging and cell-targeting capabilities. Our results demonstrate an approach toward functional and physiologically stable DNA origami for biomedical applications.},
doi = {10.1073/pnas.1919749117},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 12,
volume = 117,
place = {United States},
year = {2020},
month = {3}
}
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https://doi.org/10.1073/pnas.1919749117
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