2015 Beckman Symposium   

Ian Kline

Presentation Date:

Ian Kline

Development of a cyclooctyne-based photodynamic antibiotic for targeting Helicobacter pylori's sugars

Bowdoin College


Helicobacter pylori infects over 50% of people worldwide, causing gastric ulcers and even gastric cancer in some of these individuals. Due to the increasing prevalence of antibiotic resistant strains of H. pylori, the existing triple antibiotic treatments are becoming ineffective and successful treatment of H. pylori is increasingly challenging. We propose an antibiotic that will increase H. pylori's innate sensitivity to light by incorporating the photosensitizer protoporphyrin IX (PpIX) onto the cell membrane. Our two-step therapeutic approach involves first selectively labeling H. pylori's surface sugars with azides using a process known as metabolic oligosaccharide engineering. We then plan to covalently attach the PpIX to the H. pylori cell surface via the bioorthogonal reaction between cyclooctynes and azides. To realize this vision, we designed an antibiotic that contains three components: PpIX for photodynamic therapy, aza-dibenzocyclooctyne for reacting with azide-labeled H. pylori, and a C-FLAG peptide to increase hydrophilicity. Sucessful synthesis of the therapeutic compound has been achieved using Fmoc-based solid phase peptide synthesis and thiol-maleimide chemistry. Killing experiments are currently underway to determine the efficacy of the therapeutic at reacting with azide labeling surface sugars and inciting cell death upon exposure to light . Ultimately, this work has the potential to treat patients with antibiotic resistant strains of H. pylori with a minimally invasive endoscopic procedure that will deliver light to the photosensitized H. pylori.

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