Triple, Mutually Orthogonal Bioorthogonal Pairs through the Design of Electronically Activated Sulfamate-Containing Cycloalkynes
Name
nihms-1635398.pdf
Description
Accepted version
Size
1.83 MB
Format
Adobe PDF
Checksum (MD5)
7e27affdafffd5b90e09bd7056a76923
Author(s)
Hu, Yun
Roberts, Jessica M
Kilgore, Henry R
Mat Lani, Amirah S
Raines, Ronald T
Schomaker, Jennifer M
Date Issued
2020
Journal
Journal of the American Chemical Society
Publisher
American Chemical Society (ACS)
Citation
Hu, Yun, Roberts, Jessica M, Kilgore, Henry R, Mat Lani, Amirah S, Raines, Ronald T et al. 2020. "Triple, Mutually Orthogonal Bioorthogonal Pairs through the Design of Electronically Activated Sulfamate-Containing Cycloalkynes." Journal of the American Chemical Society, 142 (44).
Version
Author's final manuscript
Abstract
© Interest in mutually exclusive pairs of bioorthogonal labeling reagents continues to drive the design of new compounds that are capable of fast and predictable reactions. The ability to easily modify S-, N-, and O-containing cyclooctynes (SNO-OCTs) enables electronic tuning of various SNO-OCTs to influence their cycloaddition rates with Type I-III dipoles. As opposed to optimizations based on just one specific dipole class, the electrophilicity of the alkynes in SNO-OCTs can be manipulated to achieve divergent reactivities and furnish mutually orthogonal dual ligation systems. Significant reaction rate enhancements of a difluorinated SNO-OCT derivative, as compared to the parent scaffold, were noted, with the second-order rate constant in cycloadditions with diazoacetamides exceeding 5.13 M-1 s-1. Computational and experimental studies were employed to inform the design of triple ligation systems that encompass three orthogonal reactivities. Finally, polar SNO-OCTs are rapidly internalized by mammalian cells and remain functional in the cytosol for live-cell labeling, highlighting their potential for diverse in vitro and in vivo applications.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1021/JACS.0C06725
