Prof. Shabat Doron

  
Affiliation:School of chemistry
Tel:  (972)-3-6408340
 
Fax: (972)-3-6406517
 
Email: chdoron@tau.ac.il
 
Personal Website:

 
Postal Address:School of chemistry
Tel Aviv University
Tel Aviv 69978

Research Interest

Self-Immolative Molecular Systems for: Drug delivery, Diagnostic assays, Signal amplification, 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 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 demonstrate 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.

Selected Publications


  • 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”, J. Am. Chem. Soc., 2011, DOI: 10.1021/ja203145v.
  • Sella, E., Lubelski, A., Klafter, J., Shabat, D., “Two-Component Dendritic Chain Reactions: Experiment and Theory”, J. Am. Chem. Soc., 2010, 132, 3945-52.
  • Weinstain, R., Segal, E., Satchi-Fainaro, R., Shabat, D., “Real-Time Monitoring of Drug Release”, 2010, Chem. Commun., 46, 553-5.
  • Sella, E., Shabat, D., “Dendritic Chain Reaction”, J. Am. Chem. Soc. 2009, 131, 9934-6.
  • Sagi, A., Weinstain, R., Karton, N., Shabat, D., “Self-Immolative Polymers” J. Am. Chem. Soc. 2008, 130, 5434-5.
  • 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” J. Am. Chem. Soc. 2005, 127, 13104-5.
  • Amir R. J., Popkov, M., Lerner, R. A., Barbas C. F. III., Shabat, D., “Prodrug Activation Gated by a Molecular OR Logic Trigger”, Angew. Chem. Int. Ed. Engl., 2005, 44, 4378-81.
  • Haba, K., Popkov, M., Shamis, M., Lerner, R. A., Barbas C. F. III., Shabat, D., “Single-Triggered Trimeric Prodrugs”, Angew. Chem. Int. Ed. Engl., 2005, 44, 716-20.
  • Shamis, M., Lode, H.N., Shabat, D. “Bioactivation of Self-Immolative Dendritic Prodrugs by Catalytic Antibody 38C2”, J. Am. Chem. Soc., 2004, 126, 1726-31.
  • Amir, R.J., Pessah, N., Shamis, M., Shabat, D., "Self-Immolative Dendrimers". Angew. Chem. Int. Ed. Engl., 2003, 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". Angew. Chem. Int. Ed. Engl., 2003, 42, 327-332.