Ronald T. Raines

Ronald Raines

Firmenich Professor of Chemistry
Massachusetts Institute of Technology
Cambridge, MA


Ghost Proteins

The surface of mammalian cells is highly anionic. Accordingly, Coulombic repulsion prevents anionic molecules from entering cells. We have tuned the reactivity of a diazo compound to elicit the efficient O-alkylation of carboxylic acids in water. 1 Figure

Such esterification enables proteins to traverse the plasma membrane directly, like a small-molecule prodrug. 2, 3 As with prodrugs, the nascent esters are substrates for endogenous esterases that regenerate native proteins in the cytosol. The hydrolysis of nascent esters is necessary for membrane traversal. –This work was supported by grant R01 GM044783, NIH.


Ronald T. Raines


Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA


1. K. A. Mix. R. T. Raines, Org. Lett. 2015, 17, 2358–2361
2. K. A. Mix, J. E. Lomax, R. T. Raines, J. Am. Chem. Soc. 2017, 139, 14396–14398
3. V. T. Ressler, K. A. Mix, R. T. Raines, ACS Chem. Biol. 2019, In Press. doi:10.1021/acschembio.9b00033

Lecture Images

Ronald Raines presenting at APS2019 Ronald Raines presenting at APS2019 Ronald Raines presenting at APS2019