An Azidoribose Probe to Track Ketoamine Adducts in Histone Ribose Glycation

Igor Maksimovic, Igor Maksimovic, Qingfei Zheng, Marissa N. Trujillo, James J. Galligan, Yael David, Yael David, Yael David, Yael David

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Reactive cellular metabolites can modify macromolecules and form adducts known as nonenzymatic covalent modifications (NECMs). The dissection of the mechanisms, regulation, and consequences of NECMs, such as glycation, has been challenging due to the complex and often ambiguous nature of the adducts formed. Specific chemical tools are required to directly track the formation of these modifications on key targets in order to uncover their underlying physiological importance. Here, we present the novel chemoenzymatic synthesis of an active azido-modified ribose analog, 5-azidoribose (5-AR), as well as the synthesis of an inactive control derivative, 1-azidoribose (1-AR), and their application toward understanding protein ribose-glycation in vitro and in cellulo. With these new probes we found that, similar to methylglyoxal (MGO) glycation, ribose glycation specifically accumulates on histones. In addition to fluorescent labeling, we demonstrate the utility of the probe in enriching modified targets, which were identified by label-free quantitative proteomics and high-resolution MS/MS workflows. Finally, we establish that the known oncoprotein and hexose deglycase, fructosamine 3-kinase (FN3K), recognizes and facilitates the removal of 5-AR glycation adducts in live cells, supporting the dynamic regulation of ribose glycation as well as validating the probe as a new platform to monitor FN3K activity. Altogether, we demonstrate this probe's utilities to uncover ribose-glycation and deglycation events as well as track FN3K activity toward establishing its potential as a new cancer vulnerability.

Original languageEnglish (US)
Pages (from-to)9999-10007
Number of pages9
JournalJournal of the American Chemical Society
Issue number22
StatePublished - Jun 3 2020

ASJC Scopus subject areas

  • Catalysis
  • General Chemistry
  • Biochemistry
  • Colloid and Surface Chemistry


Dive into the research topics of 'An Azidoribose Probe to Track Ketoamine Adducts in Histone Ribose Glycation'. Together they form a unique fingerprint.

Cite this