ChemBio e-seminar by Prof. Justin Kim (Harvard Med School) - CH-635
Event details
| Date | 09.05.2023 |
| Hour | 16:15 › 17:15 |
| Speaker | Prof. Justin Kim |
| Location | Online |
| Category | Conferences - Seminars |
| Event Language | English |
Title: Bioorthogonal click and release: A general, rapid, reversible bioconjugation strategy employing enamine N-oxides
Abstract:
A functionally reversible bioconjugation strategy employing a new bioorthogonal dissociative reaction has been designed using enamine N-oxides. The reaction is rapid, complete, directional, traceless, and displays broad substrate scope. Reaction rates for cleavage of small molecules from proteins are fast, and the reaction is insensitive to common aqueous buffers, pHs between 4 and 10, complex tissue homogenates, and cells. Diboron reagents with bidentate and tridentate ligands also effectively reduce the enamine N-oxide to induce dissociation and compound release. This reaction can be paired with the corresponding bioorthogonal hydroamination reaction between N,N-dialkylhydroxylamines and strained or push-pull-activated alkynes to afford an integrated system of bioorthogonal click and release via an enamine N-oxide linchpin with a minimal footprint. The tandem associative and dissociative reactions are useful for the traceless and transient attachment of proteins and small molecules with access to a discrete, isolable intermediate. The effectiveness of this reversible transformation is demonstrated through several applications.
Speaker's biography:
Justin Kim received his AB in Chemistry and Physics and AM in Chemistry from Harvard College in 2007. He completed his PhD on the total synthesis of cyclotryptamine and diketopiperazine alkaloids with Prof. Mohammad Movassaghi at MIT in 2013 then pursued postdoctoral studies in chemical biology with Prof. Carolyn Bertozzi at UC Berkeley and Stanford University as a Miller Institute Fellow. In 2016, he started his faculty appointment as an assistant professor of Biological Chemistry and Molecular Pharmacology at Harvard Medical School and the Department of Cancer Biology at Dana-Farber Cancer Institute. Research in his laboratory focuses on developing biologically compatible chemistries that facilitate the study and manipulation of biomacromolecules and biomaterials.
Lab website: https://kimlab.dana-farber.org/
Abstract:
A functionally reversible bioconjugation strategy employing a new bioorthogonal dissociative reaction has been designed using enamine N-oxides. The reaction is rapid, complete, directional, traceless, and displays broad substrate scope. Reaction rates for cleavage of small molecules from proteins are fast, and the reaction is insensitive to common aqueous buffers, pHs between 4 and 10, complex tissue homogenates, and cells. Diboron reagents with bidentate and tridentate ligands also effectively reduce the enamine N-oxide to induce dissociation and compound release. This reaction can be paired with the corresponding bioorthogonal hydroamination reaction between N,N-dialkylhydroxylamines and strained or push-pull-activated alkynes to afford an integrated system of bioorthogonal click and release via an enamine N-oxide linchpin with a minimal footprint. The tandem associative and dissociative reactions are useful for the traceless and transient attachment of proteins and small molecules with access to a discrete, isolable intermediate. The effectiveness of this reversible transformation is demonstrated through several applications.
Speaker's biography:
Justin Kim received his AB in Chemistry and Physics and AM in Chemistry from Harvard College in 2007. He completed his PhD on the total synthesis of cyclotryptamine and diketopiperazine alkaloids with Prof. Mohammad Movassaghi at MIT in 2013 then pursued postdoctoral studies in chemical biology with Prof. Carolyn Bertozzi at UC Berkeley and Stanford University as a Miller Institute Fellow. In 2016, he started his faculty appointment as an assistant professor of Biological Chemistry and Molecular Pharmacology at Harvard Medical School and the Department of Cancer Biology at Dana-Farber Cancer Institute. Research in his laboratory focuses on developing biologically compatible chemistries that facilitate the study and manipulation of biomacromolecules and biomaterials.
Lab website: https://kimlab.dana-farber.org/
Practical information
- Informed public
- Free