Selective Late-Stage Functionalization of Tryptophan-Containing Peptides To Facilitate Bioorthogonal Tetrazine Ligation
Document Type
Article
Publication Date
3-18-2024
Abstract
Site-selective modification of complex peptides and the functionalization of their C–H bonds hold great promise for expanding their use in therapeutics and biomedical research. Herein, we leverage the power of late-stage chemoenzymatic catalysis using an indole prenyltransferase (IPT) enzyme and alkyl diphosphates to specifically modify the indole ring of tryptophan in clinically relevant peptides. Furthermore, the installed handle enables bioorthogonal click chemistry through an inverse electron-demand Diels–Alder (IEDDA) reaction with a biotin-conjugated tetrazine probe.
Recommended Citation
Mupparapu N, Syed B, Nguyen DN, Vo TH, Trujillo A, Elshahawi SI. Selective Late-Stage Functionalization of Tryptophan-Containing Peptides To Facilitate Bioorthogonal Tetrazine Ligation. Org Lett. 2024;26(12):2489-2494. https://doi.org/10.1021/acs.orglett.4c00709
Copyright
American Chemical Society
Comments
This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Organic Letters, volume 26, issue 12, in 2024following peer review. This article may not exactly replicate the final published version. The definitive publisher-authenticated version is available online at https://doi.org/10.1021/acs.orglett.4c00709.