Single-Trigger Molecular Amplifiers

Invention Dendrimers were synthesized, whereby a single specific cleavage event releases all the functional groups at the tips of the dendrimer, via spontaneous fragmentation of the dendrimer to its building blocks. These dendrimers, with the capacity to self destruct, have been termed Self-Immolative Dendrimers (SIDs). SIDs can be used to amplify chemical or biological signals depending upon the specific trigger, which may be cleavage by a specific enzyme, specific photo-activation of a photo-labile bond or specific chemically induced cleavage Potential Applications Dendrimers are branched, highly defined, synthetic macromolecules characterized by a large number of functional groups at the tips of their branches - the pay-load. The dendrimer is a repetitive branching structure; with the number of branching units defining the dendrimer. This structural precision makes these molecules an ideal platform for biological applications such as the amplification of molecular effects for pharmaceutical and diagnostic purposes.
Advantages
· Versatility

o The specific cleavage or trigger that initiates dendrimer fragmentation is specifically designed to suit the application.

o The degree of amplification (reflected in the final pay-load size) may be varied according to the degree of dendrimer branching.

· Wide applicability

o Suitable for both biological and chemical end uses - including drug delivery and diagnostics.

· Good solubility & stability Profiles
Stage Proof of principle has been achieved in vitro, with a number of different SIDs with various branching levels, functional pay-loads and triggers. Self-Immolative-Dendrimers with up to three branching levels were synthesized such that eight functional groups may be released per molecule with the expected first order kinetics.
References
§ Shamis, M. Lode, H.H. and Shabat, D. (2003) Activation of dendritic prodrug platform by a single enzymatic cleavage using catalytic antibody 38C2. Angewandte Chemie International Edition 42, 4494

§ Alir, R.J., Pessah, N., Shamis, M. and Shabat, D. (****) Self-Immolative-Dendrimers. *****
Patent Pending
Tech Transfer Officer Dr. Nissim Chen Office: +972-3-6406121 Fax: +972-3-6406675 Mail: [email protected]

Inventor(s): Doron Shabat

Type of Offer: Licensing



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