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bioRxiv · 10.1101/2024.02.25.581963

A Fluorogenic Green Merocyanine-Based Probe to Detect Heparanase-1 Activity

Rabinowitz, Z. M.·Wang, Z.·Liu, J.·Zhang, Y.·Jimenez Ybargollin, A.·Saketkhou, M.·Cui, L.
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Abstract

Heparanase-1 (HPSE-1), an endo-{beta}-D-glucuronidase, is an extracellular matrix (ECM) remodeling enzyme that degrades heparan sulfate (HS) chains of heparan sulfate proteoglycans (HSPGs). HPSE-1 functions to remodel the ECM and thereby disseminate cells, liberate HS-bound bioactive molecules, and release biologically active HS fragments. Being the only known enzyme for the cleavage of HS, HPSE-1 regulates a number of fundamental cellular processes including cell migration, cytokine regulation, angiogenesis, and wound healing. Overexpression of HPSE-1 has been discovered in most cancers, inflammatory diseases, viral infections, among others. As an emerging therapeutic target, the biological role of HPSE-1 remains to be explored but is hampered by a lack of research tools. To expand the chemical tool-kit of fluorogenic probes to interrogate HPSE-1 activity, we design and synthesized a fluorogenic green disaccharide-based HPSE-1 probe using our design strategy of tuning the electronic effect of the aryl aglycon. The novel probe exhibits a highly sensitive 278-fold fluorescence turn-on response in the presence of recombinant human HPSE-1, while emitting green light at 560 nm, enabling the fluorescence imaging of HPSE-1 activity in cells.

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Rabinowitz, Z. M., Wang, Z., Liu, J., Zhang, Y., Jimenez Ybargollin, A., Saketkhou, M., Cui, L.. 2024-02-26. A Fluorogenic Green Merocyanine-Based Probe to Detect Heparanase-1 Activity. https://doi.org/10.1101/2024.02.25.581963

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