Spicer Lab (@spicerlab.bsky.social)

Our latest paper from Lydia and @kstankevich.bsky.social is out in JACS Au! We wanted better reagents for selectively labelling protein N-termini, so looked at how functionalisation affected each step of the complex equilibrium, leading to faster and more stable probes. pubs.acs.org/doi/10.1021/...

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Effect of Pyridinecarboxaldehyde Functionalization on Reactivity and N-Terminal Protein Modification 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. https://pubs.acs.org/doi/10.1021/jacsau.5c00238