Herein, we describe the synthesis and structure–activity relationships of cyclic peptides designed to target heat shock protein 90 (Hsp90). Generating 19 compounds and evaluating their binding affinity reveals that increasing electrostatic interactions allows the compounds to bind more effectively with Hsp90 compared to the lead structure. Exchanging specific residues for lysine improves binding affinity for Hsp90, indicating some residues are not critical for interacting with the target, whereas others are essential. Replacing l- for d-amino acids produced compounds with decreased binding affinity compared to the parent structure, confirming the importance of conformation and identifying key residues most important for binding. Thus, a specific conformation and electrostatic interactions are required in order for these inhibitors to bind to Hsp90.

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Fusobacterium nucleatum may be implicated in cases of emphysematous cholecystitis (EC) and carries a high mortality risk, especially in individuals with heart disease, renal insufficiency, and underlying malignancy. Fusobacterium infections are rarely detected in the setting of cholecystitis possibly due to the difficulty with properly culturing the bacteria. We describe a case of a patient with EC in whom blood cultures were positive for growth of F. nucleatum in one of two samples. The patient was treated with empiric antibiotic therapy consisting of metronidazole and cefepime. In patients with EC and negative cultures, it is possible that they may have an undetected infection with fusobacteria, which carries a high mortality risk. As such, clinicians should maintain a high degree of suspicion of obligate anaerobic infection in patients who have negative blood culture for growth in the setting of EC and consider continuation of adequate antimicrobial coverage.