The guanidiniocarbonylpyrrole–fluorophore conjugates as theragnostic tools for dipeptidyl peptidase III monitoring and inhibition

Abstract

Study of seven new guanidiniocarbonylpyrrole (GCP)–fluorophore conjugates interactions with dipeptidyl peptidase III (DPP III) showed that all compounds bind strongly (K_s ≈ µM) to enzyme active site, but with very different fluorimetric response (varying from quenching to strong increase), dependent on the fluorophore type and intramolecular pre-organisation of molecule. Positively charged lysine side chain improved significantly compound solubility but diminished fluorescence increase upon DPP III binding and completely abolished inhibitory effect on DPP III activity, whereas linker-neutral analogues showed stronger emission increase and were efficient enzyme inhibitors. By far the best fluorimetric response and inhibitive properties showed cyanine–GCP analogue, thus being promising lead compound for both enzyme sensing and bio-activity inhibiting (theragnostic) studies of DPP III in the future.

Communicated by Ramaswamy H. Sarma

Keywords:

• DPP III inhibitor
• fluorescence
• pyrene
• cyanine
• guanidiniocarbonyl-pyrrole

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Acknowledgements

We thank Peter Macheroux team (TU-Graz, Austria) for valuable support and discussions and Marko Tomin for his help with AutoDock program.

Additional information

Funding

The work has been supported by Croatian Science Foundation projects: IP-2018-01-2936 and IP-2018-01-5475.