Synthesis and post-polymerisation ligations of PEG-based hyperbranched polymers for RNA conjugation via reversible disulfide linkage

Ardana, Aditya, Whittaker, Andrew K. and Thurecht, Kristofer J. (2017) Synthesis and post-polymerisation ligations of PEG-based hyperbranched polymers for RNA conjugation via reversible disulfide linkage. Macromolecular Research, 25 6: 599-614. doi:10.1007/s13233-017-5111-z


Author Ardana, Aditya
Whittaker, Andrew K.
Thurecht, Kristofer J.
Title Synthesis and post-polymerisation ligations of PEG-based hyperbranched polymers for RNA conjugation via reversible disulfide linkage
Formatted title
Synthesis and post-polymerisation ligations of PEG-based hyperbranched polymers for RNA conjugation via reversible disulfide linkage
Journal name Macromolecular Research   Check publisher's open access policy
ISSN 1598-5032
2092-7673
Publication date 2017-06-01
Sub-type Article (original research)
DOI 10.1007/s13233-017-5111-z
Open Access Status Not yet assessed
Volume 25
Issue 6
Start page 599
End page 614
Total pages 16
Place of publication Seoul, Republic of Korea
Publisher Polymer Society of Korea
Language eng
Abstract The synthesis of architectural polymers with multiple reactive functionalities offers significant promise as platform technologies for development of nano-medicines that require hybrid biomolecule-nanomaterial components. However, there can often be a mismatch in compatibility between the conditions required for the coupling chemistry, while maintaining stability of the biomolecule. This leads to decreased yields and poor functional fidelity. In this report, we describe the synthesis of hyperbranched polymers, where reversible addition fragmentation chaintransfer (RAFT) polymerization is used to control chain molecular weight, end group functionality and the final size of the hyperbranched polymer. Through optimization of the reaction conditions, we demonstrate that branched polymers with controlled size can be synthesized. The subsequent modification of the end-groups within the branched polymer through coupling to small oligonucleotides is then systematically investigated as a function of coupling chemistry. We demonstrate that to achieve the highest degree of coupling, chain extension of the end-group away from the sterically-hindered core of the polymer is required, and that the use of strained alkyne-azide coupling reactions appear to show the highest level of efficiency under the conditions studied. Indeed, when mixed attachment of both fluorescent dye molecules and oligos is attempted under these conditions, almost quantitative end-group modification is achieved. Overall, we highlight the importance of choosing compatible chemistries that allow efficient coupling of biomolecules to synthetic substrates under mild conditions to achieve optimal reaction performance.
Keyword Polymer-siRNA conjugate
Hyperbranched polymer
Reversible addition fragmentation chain transfer
Bionanomaterial
Living radical polymerization
Transfer raft polymerization
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Australian Institute for Bioengineering and Nanotechnology Publications
Centre for Advanced Imaging Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 0 times in Thomson Reuters Web of Science Article
Scopus Citation Count Cited 0 times in Scopus Article
Google Scholar Search Google Scholar
Created: Mon, 14 Aug 2017, 01:00:25 EST by System User on behalf of Learning and Research Services (UQ Library)