Prof. SHABAT Doron
Self-immolative dendrimers are unique structural molecules that can release all of their tail units, through a domino-like chain fragmentation, which is initiated by a single cleavage at the dendrimer's core. Incorporation of drug molecules as the tail units and an enzyme substrate as the trigger, can generate a multi-prodrug unit that is activated with a single enzymatic cleavage. Dendritic prodrugs, activated through a single catalytic reaction by a specific enzyme, were shown to present significant advantages in the inhibition of tumor growth, especially if the targeted or secreted enzyme exists at relatively low levels in the malignant tissue. Self-immolative dendrimers were also applied as a general platform for biosensor molecules, which are used to detect/amplify enzymatic activity.
Smart polymers are special kinds of polymeric molecules that respond to external stimuli. We have developed a novel smart polymer designed to sequentially disassemble into its building blocks upon initiation by a triggering event at the polymer head. The polymer structure is based on a polycarbamate backbone that disassembles through a domino-like, 1,6-elimination and decarboxylation reactions. To demonstrate the concept, we synthesized a self-immolative polymer that amplifies a single cleavage reaction into multiple-release of fluorogenic molecules and confirmed the head to tail disassembly concept. These polymers can be used to prepare highly sensitive molecular sensors with large signal-to-noise ratios. The sensors should be useful for the detection of a wide range of biological and chemical activities through use of the appropriate trigger at the polymer-head.