Development of a DNP-MRI molecular probe for detecting dipeptidyl peptidase-4 activity in vivo based on the substrate recognition mechanism.

Motivation: Dipeptidyl peptidase-4 (DPP-4) is a biologically important peptidase known as a biomarker and therapeutic target for type 2 diabetes and cancers. Therefore, detection of DPP-4 activity can be a useful method for early diagnosis and treatment efficacy assessment. Goal(s): Development of a DNP-MRI molecular probe for detecting DPP-4 activity in vivo Approach: We performed molecular designs of DNP-MRI molecular probes for meeting physicochemical properties. For evaluation of enzymatic reactivity of the probes, enzymatic reaction parameters (Km, kcat) were measured. The optimized probe was applied for DNP-MRI experiments using mice. Results: We developed a DNP-MRI molecular probe to detect DPP-4 activity in vivo. Impact: With design strategy based on recognition mechanism, we have developed a DNP-MRI molecular probe against DPP-4, which has been difficult to develop so far. New probe enables detection of DPP-4 activity in vivo and will be useful for medical applications.