Ronald T Raines
Massachusetts Institute of Technology, MA·Chemistry
Nearly all drugs that act inside cells are small molecules, because large, charged proteins cannot slip across the fatty membrane that surrounds a cell. The handful of protein drugs in use, mostly antibodies, hormones and enzymes, work outside cells.
- Fields
Chemistry
Biochemistry
Pharmacology
- Topics
protein chemistry
protein esterification
diazo compounds
- Grants
- 1 known grant, through Jan 2028
What they work on
- Define the fundamentals of protein esterification, using tuned diazo compounds that esterify protein carboxyl groups in water, and determine how the resulting proteins are taken up by human cells.
- Characterize the enzymology of ester hydrolysis by intracellular esterases, testing whether removal of the ester groups is traceless and leaves protein function intact.
- Test the generality of esterification-based delivery by using it to carry proteins that cause cell death or suppress tumors, and proteins that control genome editing, into human cells.
- Extend the chemistry to anchor oligonucleotides and other beneficial groups on cell surfaces and to generalize the selective degradation of chosen cellular proteins.
More about the research
Giving proteins the ability to enter cells would open up targets inside them, and that is the goal of this research program.
Why it matters
If proteins can be chemically disguised to enter cells and then restored to full activity, whole classes of therapeutic proteins that currently work only outside cells could reach internal targets, including proteins that suppress tumors or control gene editing. The same chemistry could give biologists general tools for decorating cell surfaces and for selectively removing a chosen protein from a cell.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Qiaobing Xu
Tufts University, MA·Biomedical Engineering
Covalently attach a ligand that binds the target protein onto an E3 ligase-related protein, creating a two-part degrader that avoids the PROTAC hook effect.
Jaewon Chang
Emory University, GA·Chemistry
Design and synthesize covalent warheads that react with lysine, tyrosine and serine residues on E3 ubiquitin ligases, the enzymes that tag proteins for destruction, going beyond the cysteine-reactive chemistry used so far.
Weiping Tang
University of Wisconsin-Madison, WI·Chemistry
Synthesize conjugates that link folate, a ligand for the cancer-overexpressed folate receptor, to antibodies against PD-L1, and test how well they degrade PD-L1 in cancer cells.
The school
Massachusetts Institute of Technology: 25 labs on PI Pages, $1.1B a year on research, 692 research doctorates a year.
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