Chemical glycoproteomics

Mucins are heavily glycosylated proteins that have been known to play roles in inflammation and cancer with potential to be therapeutic targets for future treatments1. Probing the mucinome is something that the Bertozzi lab has worked towards since 2002 in the form of mucin-type O-glycoproteomics technology development. To build upon these accomplishments, I will work towards the development of a new mucin-selective enrichment strategy for mass spectrometry analysis of the “mucinome” by utilizing a novel proximity labeling approach6. To do this, I will develop a StcE[E447D] mucinase with an iridium photocatalyst conjugate which will catalyze the labeling of mucin domain containing proteins with a biotin probe which can then be enriched. The conjugated StcE[E447D] mucinase will be validated utilizing mass spectrometry glycoproteomics in prostate cancer cell models. Finally, I will also expand upon the existing library of inactive mucinases by adding inactive mucinases with photocatalyst conjugates.