Thioamide-based fluorescent sensors for dipeptidyl peptidase 4

Area of Science:

• Biochemistry
• Analytical Chemistry
• Biomedical Science

Background:

• Dipeptidyl peptidase 4 (DPP-4) is recognized as a significant biomarker.
• DPP-4 is implicated in both cancer and metabolic diseases.
• Accurate measurement of DPP-4 activity is crucial for diagnostic and research purposes.

Purpose of the Study:

• To design and synthesize novel fluorescent probes for Dipeptidyl peptidase 4 (DPP-4).
• To utilize a thioamide as a quencher in the probe design.
• To enable measurement of DPP-4 kinetics, inhibition, and activity in biological samples.

Main Methods:

• Development of fluorescent probes based on native protease substrates.
• Incorporation of a thioamide functional group as a quencher.
• In vitro assays for enzyme kinetics and inhibition studies.
• Measurement of DPP-4 activity in human saliva samples.

Main Results:

• Successful design and synthesis of novel DPP-4-specific fluorescent probes.
• Demonstration of probe utility in measuring enzyme kinetics.
• Validation of probe's ability to detect inhibition by sitagliptin.
• Quantification of DPP-4 activity in saliva samples using the developed probes.

Conclusions:

• The novel fluorescent probes are effective tools for studying DPP-4.
• These probes facilitate the assessment of DPP-4 activity and inhibition.
• The developed methodology shows potential for biomarker discovery in cancer and metabolic diseases.