Federal Grant Award Summary

Brandeis University received a $398,904 Project Grant from the National Institute of General Medical Sciences (NIGMS) under the Biomedical Research and Research Training program (CFDA 93.859), awarded July 8, 2026, with completion targeted for February 28, 2031. The award supports research to synthesize thioaminoketal antimicrobial peptides—a class of cyclic, sulfur-to-alpha-carbon thioether crosslinked peptides (sactipeptides) with antibiotic properties—and to elucidate their mechanism of action against resistant bacterial strains. The research will employ novel selective thiolation methods to convert linear peptides to sactipeptides, enabling the first chemical synthesis of this peptide class and facilitating the preparation of simpler natural products and analogs for targeted molecular studies.

The project will deliver four classes of bioactive cyclic peptides of increasing structural complexity, with particular focus on candidates demonstrating potent broad-spectrum antimicrobial activity and efficacy against drug-resistant pathogens including vancomycin-resistant Enterococcus and Clostridium difficile. Deliverables include detailed structure-activity relationship data derived from testing synthetic linear sactipeptides and oxygen analogs to evaluate the effects of ketal structure on bioactivity, culminating in the design and synthesis of new sactipeptide analogs optimized for antibiotic development. These research outputs aim to overcome existing synthesis limitations and knowledge gaps regarding stereochemical configuration and bacterial mechanisms of action that have historically impeded development of this peptide class as next-generation antibiotics.