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Phospholipid-Based Prodrugs for Drug Targeting in Inflammatory Bowel Disease: Computational Optimization and In-Vitro Correlation

[ Vol. 16 , Issue. 23 ]


Arik Dahan, Shimon Ben-Shabat, Noa Cohen, Shahar Keinan, Igor Kurnikov, Aaron Aponick and Ellen M. Zimmermann   Pages 2543 - 2548 ( 6 )


In inflammatory bowel disease (IBD) patients, the enzyme phospholipase A2 (PLA2) is overexpressed in the inflamed intestinal tissue, and hence may be exploited as a prodrug-activating enzyme allowing drug targeting to the site(s) of gut inflammation. The purpose of this work was to develop powerful modern computational approaches, to allow optimized a-priori design of phospholipid (PL) based prodrugs for IBD drug targeting. We performed simulations that predict the activation of PL-drug conjugates by PLA2 with both human and bee venom PLA2. The calculated results correlated well with in-vitro experimental data. In conclusion, a-priori drug design using a computational approach complements and extends experimentally derived data, and may improve resource utilization and speed drug development.


Drug targeting, Inflammatory bowel disease (IBD), Molecular Dynamics, Phospholipase A2 (PLA2), Prodrugactivating enzyme, Thermodynamic integration, Umbrella Sampling/WHAM methods.


Department of Clinical Pharmacology, School of Pharmacy, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel., Department of Medicine, University of Florida, Gainesville, FL 32608, USA.

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