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Modular Design Platform for Activatable Fluorescence Probes Targeting Carboxypeptidases Based on ProTide Chemistry.

Yugo Kuriki1, Mari Sogawa1, Toru Komatsu1

  • 1Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.

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|December 18, 2023
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Summary
This summary is machine-generated.

Researchers developed a new modular platform for creating tunable fluorescence probes targeting carboxypeptidases (CPs). This innovation allows for flexible probe design, aiding biological and medical research into CP functions.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Chemical Biology

Background:

  • Carboxypeptidases (CPs) are hydrolases crucial for physiological and pathological processes.
  • Existing fluorescence probes for CPs are limited, necessitating a versatile design platform.

Purpose of the Study:

  • To establish a modular design platform for carboxypeptidase-targeting fluorescence probes.
  • To enable flexible tuning of probe properties for diverse biological and medical applications.

Main Methods:

  • Utilized ProTide chemistry, adapting its prodrug activation mechanism for probe design.
  • Developed a four-module system (fluorophore, phosphorus substituent, P1 linker amino acid, P1' substrate amino acid) for customizable probes.
  • Optimized probe reactivity by modifying the P1 linker amino acid.

Main Results:

  • Successfully constructed and validated fluorescence probes for carboxypeptidase M (CPM) and prostate-specific membrane antigen (PSMA).
  • Demonstrated the probes' efficacy in imaging CP activity in live cells and patient clinical specimens.
  • Showcased the platform's ability to fine-tune probe properties, including reactivity and emission wavelength.

Conclusions:

  • The ProTide-based modular platform offers a flexible strategy for developing novel carboxypeptidase-targeting fluorescence probes.
  • This approach facilitates the study of CP-related biological functions and pathological conditions.
  • The developed probes are valuable tools for in vitro and in vivo imaging applications.