Tel Aviv University (TAU)- Research Group
Prof. Doron Shabat
The Raymond and Beverly Sackler School of Chemistry
The Faculty of Exact Sciences
Prof. Doron Shabat, Ph.D.
Office phone: 972-3-6408340
Lab phone: 972-3-6406548
Office fax: 972-3-6406517
School of Chemistry
Tel-Aviv 69978, Israel
Self-Immolative Molecular Systems for: Drug delivery, Diagnostic assays, Signal amplification and NIR imaging.
During the course of our work at Tel-Aviv University, we have developed novel molecular systems with self-immolative capabilities. The ability of a molecule to undergo spontaneous domino-like disassembly upon a stimulus event is referred as a self-immolative feature. Initially, we developed a chemical adaptor system for targeted prodrug approach. The prodrug is disassembled of the targeting moiety to release the active drug upon a triggering event. Next, we developed dendrimers with self-immolative capabilities and later, we extended this approach to linear polymers and comb polymers. We also introduced a novel technique for exponential amplification of diagnostic signals. This technique is based on a distinctive dendritic chain reaction (DCR) and has the potential to detect a single molecule activity. Recently, we become interested in the field of Near-Infrared imaging. We developed a novel paradigm for obtaining a Turn-ON mechanism in cyanine dyes and demonstrated this concept for noninvasive optical imaging of inflammation in animal-model.
Self-immolative dendrimers, as shown in the picture, spontaneously release all the end-group molecules (drug or diagnostic units) following a single activation event at the focal point. This triggering event induces a cascade of self-eliminations, which leads to complete dissociation of the dendrimer into its separate building blocks.
Redy O, Shabat D. Modular theranostic prodrug based on a FRET-activated self-immolative linker. (2012) J Control Release.
Redy O, Kisin-Finfer E, Sella E, Shabat D. A simple FRET-based modular design for diagnostic probes. (2012) Org Biomol Chem. 10:710-715.
Perry-Feigenbaum R, Sella E, Shabat D. Autoinductive exponential signal amplification: a diagnostic probe for direct detection of fluoride. (2011) Chemistry. 17:12123-12128.
Karton-Lifshin, N., Segal, E., Omer, L., Portnoy, M., Satchi-Fainaro, R., Shabat, D. A Unique Paradigm for a Turn-ON Near-Infrared Cyanine-Based Probe: Non-Invasive Intravital Optical Imaging of Hydrogen Peroxide. (2011) J. Am. Chem. Soc. 133:10960-10965.
Sella, E., Lubelski, A., Klafter, J., Shabat, D., Two-Component Dendritic Chain Reactions: Experiment and Theory. (2010) J. Am. Chem. Soc. 132, 3945-3952.
Weinstain, R., Segal, E., Satchi-Fainaro, R., Shabat, D., Real-Time Monitoring of Drug Release, (2010), Chem. Commun. 46, 553-555.
Sella, E., Shabat, D., Dendritic Chain Reaction. (2009) J. Am. Chem. Soc. 131, 9934-9936.
Sagi, A., Weinstain, R., Karton, N., Shabat, D., Self-Immolative Polymers. (2008) J. Am. Chem. Soc. 130, 5434-5435.
Weinstain, R., Lerner, R. A., Barbas C. F. III., Shabat, D., Antibody-Catalyzed Asymmetric Intramolecular Michael Addition of Aldehydes and Ketones to Yield the disfavoured Cis-Product. (2005) J. Am. Chem. Soc., 127, 13104-13105.
Amir R. J., Popkov, M., Lerner, R. A., Barbas C. F. III., Shabat, D., Prodrug Activation Gated by a Molecular OR Logic Trigger. (2005) Angew. Chem. Int. Ed. Engl. 44, 4378-4381.
Haba, K., Popkov, M., Shamis, M., Lerner, R. A., Barbas C. F. III., Shabat, D. Single-Triggered Trimeric Prodrugs. (2005) Angew. Chem. Int. Ed. Engl. 44, 716-720.
Shamis, M., Lode, H.N., Shabat, D. Bioactivation of Self-Immolative Dendritic Prodrugs by Catalytic Antibody 38C2. (2004) J. Am. Chem. Soc. 126, 1726-1731. Amir, R.J., Pessah, N., Shamis, M., Shabat, D., Self-Immolative Dendrimers. (2003) Angew. Chem. Int. Ed. Engl. 42, 4494-4499.
Gopin, A., Pessah, N., Shamis, M., Rader, C., and Shabat, D. A chemical adaptor system designed to link a tumor-targeting device with a prodrug and an enzymatic trigger. (2003) Angew. Chem. Int. Ed. Engl. 42, 327-332.
Tel Aviv University (TAU)
Ben-Gurion University of the Negev (BGU)
The Hebrew University of Jerusalem (HUJI)
Bar-Ilan University (BIU)