02 Juillet 2024

Séminaire DMO et DON présenté par Prof. Pik Kwan Lo

Titre : "Design, Synthesis and Applications of Photoactivable Nucleic Acids in DNA technology"

orateur : Prof. Pik Kwan Lo
Department of Chemistry and State Key Laboratory of Marine Pollution, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong SAR, China
Key Laboratory of Biochip Technology, Biotech and Health Care, Shenzhen Research Institute of City University of Hong Kong, 518057, Shenzhen, China

Résumé : DNA is emerging as a powerful and versatile nanoscale building block for the construction of precisely self-assembled nanostructures due to its desirable molecular recognition property, precise nucleobase sequence control, ease of chemical functionalization, and sensitive stimuli responsiveness. Light is the most promising non-invasive regulating input because it enables remote control of reaction systems with high spatial and temporal precision and without causing pollution. However, the synthesis of many reported photon photoactive groups does not allow for oligonucleotide conjugation, as they are often restricted to mono-functionalization. Moreover, these groups face limitations due to experimental and synthetic complexities. In this talk, I will present my research divided into three parts: (1) Redesigning the synthetic pathways of these photoactive molecules and synthesizing a series of bi-functional two-photon photocleavable phosphoramidite molecules using typical chemical reactions. (2) Effectively introducing these molecules to DNA strands at any sequence position through standard solid-phase synthesis using well-established cyanoethylphosphoramidite chemistry. This will allow the formation of light-activatable nucleic acids. (3) Utilizing these photocleavable nucleic acids as building scaffolds for the construction of DNA-based nanocarriers, which can be used for light-triggered cargo release. Additionally, they can serve as light-cleavable linkers in the construction of DNA devices that mimic the functions of Boolean logic gates. These devices can perform logic operations such as AND, OR, NOR, and NAND gates in response to different wavelengths of light inputs.



References
1.    H. M. Leung, L. S. Liu, Y. Cai, X. Li, Y. Huang, H. C. Chu, Y R. Chin, P. K. Lo.* “Light-Activated Nanodiamond-Based Drug Delivery Systems for Spatiotemporal Release of Antisense Oligonucleotides” Bioconjugate Chem. 2024, In press. DOI: 10.1021/acs.bioconjchem.4c00087.
2.    L. S. Liu, H. M. Leung, C. Morville; H. C. Chu, J. Y. Tee, A. Specht*, F. Bolze*, P. K. Lo*. “Wavelength-Dependent, Orthogonal Photoregulation of DNA Liberation for Logic Operations” ACS Applied Material & Interfaces 2023, 15, 1, 1944–1957.
3.    D. Y. Tam, X. Zhuang, S. W. Wong, P. K. Lo. “Photo-Responsive Self-Assembled DNA Nanomaterials: Design, Working Principles and Applications” Small 2019, 15, 1805481
4.    Z. Dai, P. K. Lo. “Photo-switchable patterning of gold nanoparticles along 3D DNA nanotubes” Nanoscale 2018, 10, 5431-5435.
5.    Z. Dai, H. M. Leung, P. K. Lo. “Stimuli-Responsive Self-Assembled DNA Nanomaterials for Biomedical Applications” Small 2017, 13, 1602881.
6.    D. Y. Tam, Z. Dai, M. S. Chan, L. S. Liu, M. C. Cheung, F. Bolze, C. Tin, P. K. Lo. “A Reversible DNA Logic Gate Platform Operated by One- and Two-Photon Excitations” Angew. Chem. Int. Ed. 2016, 55, 1, 164-168.
7.    Z. Dai, D. Y. Tam, H. Xu, M. S. Chan, L. S. Liu, F, Bolze, X. H. Sun, P. K. Lo. “Conformational Change of Self-Assembled DNA Nanotubes Induced by Two-Photon Excitation” Small 2015, 11, 33, 4090-4096.


If you are interested to meet the speaker, please contact: stephane.mery@ipcms.unistra.fr

02 Juillet 2024, 10h3012h00
Auditorium de l'IPCMS

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