Redox Targets for Phosphine-Boranes

Understanding the complex mechanisms underlying redox-mediated biological processes is a fundamental pillar of cellular biology. We describe the identification and quantification of disulfide formation and reduction in response to phosphine-borane complexes. We illustrate the specific cysteine reduction effects of the novel phosphine-borane complex bis(3-propionic acid methyl ester) phenylphosphine-borane complex (PB1) on cultured 661W cells. A total of 1073 unique protein fragments from 628 unique proteins were identified and quantified, of which 13 were found to be statistically significant in comparison to control cells. Among the 13 identified proteins were Notch1, HDAC1, UBA1, USP7, and subunits L4 and L7 of the 60S ribosomal subunit, all of which are involved in redox or cell death-associated pathways. Leveraging the ability of tandem mass tagging mass spectrometry to provide quantitative data in an exploratory manner provides insight into the effect PB1 and other phosphine-borane compounds may have on the cysteine redoxome.