University of Groningen
Surface supported dynamic combinatorial chemistry for biomacromolecule recognition
Miao, Xiaoming
DOI:
10.33612/diss.99692802
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Publication date: 2019
Link to publication in University of Groningen/UMCG research database
Citation for published version (APA):
Miao, X. (2019). Surface supported dynamic combinatorial chemistry for biomacromolecule recognition. University of Groningen. https://doi.org/10.33612/diss.99692802
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Summary
122
Summary
In this thesis, DCC based selective chemical functionalization of nanomaterials is investigated. The thesis is divided into three main chapters dealing with the preparation of water-dispersed nanoparticles (chapter 2), dynamic hydrazone exchange on the surface of dendrimers (chapter 3) and specific functionalization of dendrimers by dynamic imine chemistry (chapter 4).
In chapter 2, SPIONs coated with zwitterionic ligands have been synthesized, which remained stable in aqueous solution over a long time span (> 60 days). Specifically, a choline phosphate based zwitterionic ligand carrying an aldehyde group enabled the surface functionalization by hydrazone chemistry, which demonstrates the potential of SPIONs as a new platform for surface supported DCC.
In chapter 3 we could demonstrate reversible hydrazone chemistry on zwitterionic dendrimers (PAMAM). The exchange behavior and thermodynamic equilibrium was first verified by NMR and UPLC, while after the addition of three DNA oligonucleotides templates, the amplification of the library members with higher affinities towards these DNA templates was observed. A positively charged hydrazone on the surface of PAMAM showed specifically strong amplification presumably due to its ability to bind to the negatively charged DNA.
In chapter 4, we have shown dynamic imine chemistry on the surface of zwitterionic dendrimers. Several different single and double stranded DNA oligonucleotides were applied as templates to direct the surface functionalization of the dendrimers. The synthesis of three DCLs, which were exposed to different DNA templates, was scaled-up to enable dendrimer isolation and determination of binding affinities by ITC. These binding studies indicated that the templated libraries had stronger binding affinities and better selectivity compared to the untemplated libraries. This illustrates that DCC provides a facile and efficient method to generate specific receptors to bind DNA, in one case even sequence-selectively. More in-depth studies in the future will show to which degree DCC based approaches are capable to distinguish DNA or peptide sequences in a more sequence specific manner. High selectivity would allow exciting down-stream applications, including the specific recognition of a broad array of relevant biological and medical targets.
