Oliver Torvald

Development of Auto-Immolative Spacers for Probes of Enzyme Activity
Oliver Torvald Thorn-Seshold

Key steps in biological processes and disease are often performed by specific enzymes. Molecular Imaging of the activity of target enzymes in cells and tissues is therefore important both for fundamental research and in applied medicine.[1] It is essential to develop probe technologies ensuring maximum detection sensitivity; and off ON enzyme-responsive probes, offering zero background signal plus catalytic activation by the target enzyme, are prime candidates to deliver it.[2]

We present three systems of intelligent spacers which are designed for use in off ON probes for hydrolases. Spacers of family 1 are applied to off ON aminopeptidase fluorescence probes which may give absolute signal-to-background sensitivity in vitro of over 1000:1 during a period of >24 hours.[3,4] Spacers of families 2 and 3 are under evaluation for off ON glycosidase magnetic probes. All these families of intelligent spacers may find other applications as general chemical adaptors[5] to achieve a variety of molecular logic-gating functions.

[1] E. Boonacker, C. J. F. Van Noorden, J. Histochem. Cytochem., 2001, 49, 1473-1486.
[2] M. Baker, Nature, 2010, 463, 977-980.
[3] J. Hasserodt, O. Thorn-Seshold; FR1158732, 2011.
[4] O. Thorn-Seshold, M. Vargas-Sanchez, S. McKeon, J. Hasserodt; Chem. Commun. 2012, 48, 6253-6255.
[5] D. Shabat, R. J. Amir, A. Gopin, N. Pessah, M. Shamis; Chem.–Eur. J 2004, 10, 2626-2634.