Tufts University

Department of Chemistry

62 Talbot Avenue
Medford, MA 02155
(617) 627-3441


Tufts University, Department of Chemistry

The Kritzer lab uses peptides to solve vital chemical and biomedical problems.  Peptides are discovered, developed and applied using cross-disciplinary approaches including genetics, cell biology, organic synthesis, structural biology and biophysical chemistry.

The last half-century has seen a revolution in how we understand and treat disease.  The modern plan of attack is to understand disease at the molecular level, then judiciously target key proteins in the disease process using small-molecule drugs.  However, most existing drugs target only a few types of cellular proteins such as kinases and signaling receptors.  There are many diseases that could be more effectively treated by targeting other proteins.  Such diseases include auto-immune disorders, diabetes, neurodegenerative diseases, and many currently untreatable cancers.

The Kritzer lab uses peptides and peptidomimetics (peptide-like synthetic molecules) to inhibit disease-associated proteins that would be difficult or impossible to target using traditional approaches. These molecules are an exciting and rapidly expanding area of drug development because they can target protein surfaces in ways small molecules rarely do.  In one project, we are exploring novel approaches for screening these compounds:  we use genetics to generate large libraries of cyclic peptides in living yeast cells and to screen them for those that target specific proteins or disease processes of interest.  In this manner, yeast are recruited as a virtual army of medicinal chemists capable of synthesizing and screening millions of compounds in a single week.

Discovering new bioactive peptides is only the first step, however.  In several other projects, the Kritzer lab is exploring how these powerful molecules can be modified to promote greater utility as tools for biology and chemistry.  We are exploring how intramolecular “staples” can be used to tune the reactivity of peptide-metal complexes to enable their use as chiral catalysts for important organic transformations.  We are also exploring how larger peptides can be locked into their bioactive conformation via successive application of covalent bonds as “staples.”  These bonds must be carefully designed, but when applied effectively they can make certain classes of peptides more potent, more selective, and more cell-penetrant.  This strategy is being applied to inhibitors of diverse signaling proteins involved in human cancers.  Through in-lab expertise and collaborations with biomedical scientists at Tufts University School of Medicine and other institutions in the area, the Kritzer lab simultaneously explores peptide structure, function, and anti-cancer activity.  This represents a truly multidisciplinary effort to bring these molecules to bear on intractable human diseases.