Chemistry
Tetrazine cyclized peptides for one-bead-one-compound library: Synthesis and sequencing
Document Type
Book Chapter
Abstract
While most FDA-approved peptide drugs are cyclic, robust cyclization chemistry of peptides and the deconvolution of the cyclic peptide sequences using tandem mass spectrometry render cyclic peptide drug discovery difficult. In this chapter, the protocol for the successful synthesis of tetrazine-linked cyclic peptide library in solid phase, which shows both robust cyclization and easy sequence deconvolution, is described. The protocol for the linearization and cleavage of cyclic peptides from the solid phase by simple UV light irradiation, followed by accurate sequencing using tandem mass spectrometry, is described. We describe the troubleshooting for this dithiol bis-arylation reaction and for the successful cleavage of the aryl cyclic peptide into linear form. This method for efficient solid-phase macrocyclization can be used for the rapid production of loop-based peptides and screening for inhibition of protein–protein interactions, by using the covalent inverse electron-demand Diels Alder reaction to supplement the non-covalent interaction between a protein and its peptide binder, isolating highly selective peptides in the process.
Publication Title
Methods in Enzymology
Publication Date
1-2024
Volume
698
First Page
141
Last Page
167
ISSN
0076-6879
ISBN
9780443218149
DOI
10.1016/bs.mie.2024.04.015
Keywords
Cyclic peptide, library, mass spectrometry, photocleavage, Tetrazine
Repository Citation
Das, Samir and Nag, Arundhati, "Tetrazine cyclized peptides for one-bead-one-compound library: Synthesis and sequencing" (2024). Chemistry. 36.
https://commons.clarku.edu/chemistry/36
