Matthew O'Reilly
Villanova University, PA·Chemistry·Early-career
Peptides, which are short chains of amino acids, are already used as medicines. More than 80 have been approved by the FDA, starting with insulin.
- Fields
Chemistry
Biochemistry
Pharmacology
- Topics
cyclic peptides
cyclic tetrapeptides
peptide cyclization
- Grants
- 1 known grant, through Aug 2029
What they work on
- Design arrays of cyclization reagents and screen many reaction conditions in parallel, using liquid chromatography-mass spectrometry for rapid analysis, to find reliable ways to close strained cyclic tetrapeptides.
- Use computational chemistry to evaluate how amino acid identity and stereochemistry (molecular handedness) affect the stability of strained cyclic peptides and the energy cost of ring closure, and combine the results with experimental data.
- Test auxiliary-mediated ligation, which first forms a larger, less strained ring intermediate, and test whether that intermediate contracts into the strained but more stable cyclic amide product.
- Validate the new cyclization methods by synthesizing biologically active strained cyclic peptide natural products.
More about the research
Straight-chain peptides, however, tend to break down quickly in the body and are poorly absorbed. Joining a peptide's ends into a ring (cyclizing it) often fixes these problems, but making rings by chemical synthesis is difficult. It is hardest for very short chains, because the small ring that forms is strained and the chain struggles to reach the right shape to close. This project is developing general, reproducible chemical methods for making these strained cyclic peptides so that other scientists can use them in medicine, materials and catalysis.
Why it matters
Short, strained cyclic peptides are hard to make, which limits their use despite the stability and absorption benefits that rings can give peptide drugs. Reliable synthetic methods could give chemists and chemical biologists better access to these molecules. That access could support work on new peptide-based therapeutics, materials and catalysts, and on biologically active natural products.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Gregory O'Neil
Western Washington University, WA·Chemistry
Develop stereoselective reactions using allyl organosamarium complexes, made from allylic benzoate esters or phenyl sulfones with samarium diiodide and water, to build stereogenic carbon atoms that are hard to make by other methods.
Kraig Wheeler
Whitworth University, WA·Chemistry
Synthesize families of acyclic and cyclic dipeptides and extended peptides by solid-phase peptide synthesis, systematically varying molecular shape and pendant functional groups.
Rovshan Sadygov
University of Texas Medical Branch at Galveston, TX·Biochemistry
Develop methods to estimate protein turnover from the deuterium labeling of fragment ions in tandem mass spectra, which are less distorted by space-charging, limited dynamic range and co-eluting contaminants than intact peptide ions.
The school
Villanova University: 4 labs on PI Pages, $33M a year on research, 32 research doctorates a year.
Reach out
A start for your email. Fill in the brackets.