A novel optimised sample preparation method enables high-sensitivity chemical proteomics

A newly developed free sample handling protocol for chemical proteomics from the Tate and Barnard groups dramatically boosts peptide recovery, promising up to 90-fold improvements for high-sensitivity chemical proteomics.

Chemical proteomics is a powerful tool for discovering new drug targets, but researchers often struggle with low peptide recovery when trying to enrich low-abundance proteins. A major culprit is poor sample handling: peptides frequently stick to plastic surfaces or are lost during routine vacuum evaporation, particularly when working with very low sample inputs (under 200 ng) or larger volumes.

In this latest study published in Proteomics, losses were systematically mapped across different buffers, volumes, plastics, and pH levels. In turn, a streamlined, Evotip-compatible handling protocol was developed. By directly acidifying peptides and loading them straight onto Evotips, allowing for intermediate frozen storage if needed, the new method entirely removes the need for traditional, loss-heavy vacuum evaporation steps. When peptide input was limited to just 10 nanograms, the optimized workflow delivered up to 90-fold gains in recovery compared to standard workflows that rely on vacuum evaporation.

By significantly reducing manual handling steps and mitigating plastic adsorption, this optimised method paves the way for high-throughput and high-sensitivity chemical proteomics. Crucially, it will allow researchers to characterise vital, low-abundance proteins that were previously lost during standard sample preparation.

Congratulations to Amrita, Anne, Jianan, Dasha, Ed, Anna, and Jack!