Work

Effect of Pyridinecarboxaldehyde Functionalization on Reactivity and N-Terminal Protein Modification

Year: 2025

Type: article

Abstract: The site-selective modification of protein N-termini represents a powerful strategy for producing homogeneous bioconjugates. 2-Pyridinecarboxaldehydes have emerged as a leading reagent class in this area. However, these conjugations suffer from relatively slow rates and a degree of reversibility. In this work, we therefore studied the effects of pyridinecarboxaldehyde functionalization on N-terminal modification. This allowed us to provide insight into the factors governing relative contributions from competing reaction pathways and design criteria for second generation reagents for protein labeling. Importantly, 3-methoxy-2-pyridinecarboxaldehydes were identified as providing both accelerated and more stable protein labeling, enabling further applications of this powerful technology.

Source: JACS Au

DOI: 10.1021/jacsau.5c00238

Authors: Lydia J. Barber, Ksenia S. Stankevich, Christopher D. Spicer

Institution: University of York

Language: English

Topic: Click Chemistry and Applications

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: gold

Estimated APC paid: $3,500