Welcome to the Kritzer Lab!

The goal of the Kritzer lab is to discover novel bioactive molecules and to use them to understand the molecular biology of human disease.

Discovering a new bioactive molecule is not only the first step in drug discovery, but also a sudden chance to explore previously hidden biology. The post-genomic era has seen a rapid expansion in the scope of molecule discovery, and with it an expanded role for chemists. Now, chemists are called upon not only to synthesize large collections of molecules, but also to develop novel technologies and entirely new molecular classes. The field of chemical biology has evolved to exploit this unprecedented opportunity to explore biology by perturbing it with chemical agents.

Chemical biology thus promises greater understanding of biology and disease through discovery and characterization of novel bioactive molecules. The traditional mode of discovery, small molecule high-throughput screening, has proven powerful in many cases but relies on traditional modes of drug action. This limitation means that truly novel modes of action, such as inhibition of protein-protein interactions or pharmacological chaperoning, are seldom discovered using traditional methods. This also limits the ability of traditional drug screening to discover molecules that address previously hidden biology. In addition, small molecule screening is often arduous and expensive.

The Kritzer lab takes advantage of peptide and peptidomimetic libraries to bypass many of the disadvantages of small molecule screening. Peptides and their mimetics can target protein surfaces in ways small molecules rarely do, making peptide libraries attractive for screening for nontraditional modes of action. We also explore how modifications such as substitution of peptide bonds with isosteres, amide N-methylation, and head-to-tail cyclization affect the activities, specificities, and bioavailabilities of functional peptides. By combining powerful techniques from organic synthesis, biophysical chemistry, molecular biology and genetics, we are developing new molecules and new strategies to attack cancer, inflammation, autoimmune diseases, and obesity.