p‐Azidophenylarsenoxide: An Arsenical “Bait” for the In Situ Capture and Identification of Cellular Arsenic‐Binding Proteins

Abstract

Identification of arsenic-binding proteins is important for understanding arsenic health effects and for developing arsenic-based therapeutics.W er eport here as trategy for the capture and identification of arsenic-binding proteins in living cells.W ed esigned an azide-labeled arsenical, p-azidophenylarsenoxide (PAzPAO), to serve bio-orthogonal functions:t he trivalent arsenical group binds to cellular proteins in situ, and the azide group facilitates click chemistry with dibenzylcyclooctyne.T he selective and efficient capture of arsenicbinding proteins enables subsequent enrichmenta nd identification by shotgun proteomics.A pplications of the technique are demonstrated using the A549 human lung carcinoma cells and two in vitro model systems.T he techniquee nables the capture and identification of 48 arsenic-binding proteins in A549 cells incubated with PAzPAO.A mong the identified proteins are aseries of antioxidant proteins (e.g., thioredoxin, peroxiredoxin, peroxide reductase,g lutathione reductase,a nd protein disulfide isomerase) and glyceraldehyde-3-phosphate dehydrogenase.I dentification of these functional proteins, along with studies of arsenic binding and enzymatic inhibition, points to these proteins as potential molecular targets that play important roles in arsenic-induced health effects and in cancer treatment.

Chemical Institute of Canada and Canadian Society for Chemistry Awards

“…Li is interested in studying the occurrence, human exposure, and toxicological effects of environmental contaminants. She is co‐author of a report in Angewandte Chemie on arsenic‐binding proteins …”

Preise des Chemical Institute of Canada und der Canadian Society for Chemistry

“…Li interessiert sich für das Auftreten von Umweltverunreinigungen, deren Kontakt mit Menschen und deren toxikologische Wirkungen. Sie ist Coautorin einer Veröffentlichung in der Angewandten Chemie über arsenbindende Proteine …”