Post-translational site-specific protein azidolation with an azido pyridoxal derivative

Abstract

An azido pyridoxal derivative (PLAA) was developed as a protein azidolation reagent, with selectivity towards N-terminal glycine. Successful PLAA modification was achieved with small peptide, natural proteins and lab-expressed protein...

Chemical technology principles for selective bioconjugation of proteins and antibodies

“…For example, the azido pyridoxal derivatives could offer N-Gly-specific azidolation of proteins. 238…”

“…It is an anti-inflammatory drug used to treat rheumatoid arthritis, Crohn's disease, and psoriatic arthritis. 238 Approaches utilizing PLP-mediated transamination introduce an aldehyde or a ketone at the N-terminus followed by PEGylation using the aminooxy PEG derivative in pH 6.5. 235 A single-step site-directed PEGylation can be obtained using a 2-PCA derivative which forms an imidazolidinone ring at the N-terminus (except penultimate N-Pro).…”

“…For example, the azido pyridoxal derivatives could offer N-Gly-specific azidolation of proteins. 238 These examples emphasize how multi-equilibrium processes can harness a specific combination of N a -NH 2 and proximal C a -H as a unique signature to drive the irreversible transformation. Engaging other C-H groups in reversible pathways could create opportunities for new targetome-based residue-specificity in the coming years.…”

Disintegrate (DIN) Theory Enabling Precision Engineering of Proteins

“…In another report, the Gly tag technology inspired azido pyridoxal derivatives that delivered residue-specific azidolation. 118 Engaging a unique combination of functionalities for an irreversible transformation can offer new gateways for precisely engineered bioconjugates. It would be interesting to see if chemical transformations can harness a C α -H pK a of another unique If extended to an internal residue, these approaches will likely encounter multiple solvent-accessible copies.…”

“…It also enables protein selectivity by distinguishing N -Gly from all the other N-terminal amino acids in a complex mixture of proteins. In another report, the Gly tag technology inspired azido pyridoxal derivatives that delivered residue-specific azidolation . Engaging a unique combination of functionalities for an irreversible transformation can offer new gateways for precisely engineered bioconjugates.…”