PepDNA-4D · Four-dimensional self-assembly from peptides and DNA
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2019-07-29 → 2021-07-28
- EU contribution
- €224,934
- Participants
- 1
- Scheme
- MSCA-IF-EF-ST
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Results in brief
Four-dimensional self-assembly from peptides and DNA
1. Peptide-oligonucleotide conjugates are currently explored for applications in the applied biomedical field, but their nanoscale assembly has not yet been investigated to a significant extent. Our work focused on introducing new multiscale diversity to DNA and peptide nanotechnology through orthogonal hierarchical and emergent assembly. In this work, for the first time, peptide chain elongation was achieved from a DNA strand using enzymes. The N-terminus of a phenylalanine ester unit was linked to the DNA-fragment through a succinic acid linker. Enzymatic polymerisation was then carried out using papain under mild aqueous conditions. L-glutamic acid diethyl ester was used as a monomer for polymerisation reaction. The polymerisation reaction yielded mixture of peptides and DNA-peptide conjugates both containing up to 8-mer peptide units. The formation of DNA-peptide conjugates was confirmed by mass spectrometry, and the resulting emergent assembly studied by AFM, DLS, and SEM. In conclusion, we were able to achieve elongation of peptide chain from the DNA strand for the first time, and we have demonstrated that this process affected its self-assembly. 2. There are many reports of DNA-peptide conjugation, and these are potentially medically useful molecules, but there are no reports of DNA-peptide hybrids in which the peptide chain is built chemoenzymatically, which would be much more environmentally friendly. This work established an effective conjugation method to link DNA and peptide initiator. It established a new synthetic method of synthesising peptides from the DNA strand utilising enzymes under mild reaction conditions. It also gave an opportunity to learn novel self-assembled nanostructures formed during the reaction. This reaction is a sustainable approach to synthesize DNA-peptide conjugates. The reaction is free from all hazardous and toxic reagents which makes it eco-friendly synthetic approach. This work also gives an opportunity for the scientific community to further explore self-assembly behaviours of DNA-peptide conjugates by varying different parameters and to develop novel conjugates using this approach. 3. Overall objective of this project- Introduction of chemoenzymatic polymerisation to the DNA-peptide chemistry.
Data: CORDIS, © European Union
Project objective
Structural organisation in living systems is both dynamic (varies with time), and emergent (more than the sum of its parts). Different blends of these aspects can be said to contribute to all the uniquely impressive processes of cellular biology. In contrast, synthetic self-assembled chemical systems rarely express each of these properties, being largely based on single self-assembly systems (e.g. DNA hybridisation or metal coordination), and static (i.e. observed at its thermodynamic minimum). This Fellowship will combine the Fellow's skills in chemoenzymatic peptide synthesis with those of the Supervisor in combining complementary self-assembly systems to obtain emergent superstructures. These studies will result in the first instances of dynamic and emergent self-assembly in synthetic chemical systems.To achieve this aim, we will perform chemoenzymatic polymerisation of peptides from the end of DNA backbones. Both units are capable of their own self-assembly - DNA through hybridisation, and peptides via secondary structures. In any 'static' snapshot of the system, the indirect interplay of DNA and peptide assembly will lead to highly unusual nanostructures. However, this work will go beyond, to measure the type and extent of self-assembly during the enzymatic polymerisation process using cutting edge techniques such as liquid-cell electron microscopy. The resultant systems will recapitulate the properties of living matter in these respects.In the course of these studies, the Fellow's professional skills will be honed through mentorship, the practice of taking a leading role in research, and through training courses offered by the Host Institution. At the end of the Fellowship, he will be ideally placed to assume an independent academic position.
Original text from CORDIS.
Participants
- UNIVERSITY OF KENT · Canterbury, KentCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union