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NIH Funds Fasan Group’s Research on Macrocyclic Peptide Technologies

Professor Rudi Fasan and his group have been awarded a new 4-year, $1.3 million R01 grant by the National Institutes of Health (NIGMS) to develop new technologies for the discovery of selective macrocyclic peptide inhibitors of proteins and protein-mediated interactions.  The mission of the NIH program sponsoring this research is to support the development of highly innovative technologies that will address significant opportunities to enable the advancement of biomedical research.

Protein-mediated interactions with other proteins or nucleic acids control all processes inside a cell, ranging from gene regulation to cell proliferation and apoptosis. Many diseases, including various forms of cancer, arise from or depend upon aberrantly misregulated protein-mediated interactions. Chemical agents capable of targeting and disrupting these biomolecular interactions can provide invaluable tools for the study of cellular pathways as well as starting points for the development of new therapeutics, but the development of such compounds has represented a major challenge in chemical biology and drug discovery. The Fasan group has pioneered new methodologies for the synthesis and combinatorial diversification of macrocyclic peptides, a class of molecules well suited for disrupting protein-protein interactions. These strategies has recently enabled the discovery of a first-in-class potent inhibitor of a protein-protein interaction implicated in the activation of the Hedgehog signaling pathway, an achievement published in the Journal of the American Chemical Society and highlighted in the   and elsewhere. The newly NIH-funded research will aim at implementing efficient and broadly applicable high-throughput platforms for the discovery and optimization of macrocyclic peptide agents active against a variety of target proteins. These technologies are expected to provide powerful, new tools for the generation of chemical  probes for basic research and of lead compounds for drug development.

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