Peripherally restricted PICK1 inhibitor mPD5 ameliorates pain behaviors in murine inflammatory and neuropathic pain models

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Peripherally restricted PICK1 inhibitor mPD5 ameliorates pain behaviors in murine inflammatory and neuropathic pain models

JCI Insight 2024
Jensen, Lindegaard Madsen, et.al.

This study developed and characterized mPD5, a myristoylated bivalent peptide inhibitor of the scaffold protein PICK1, showing that subcutaneous dosing relieved mechanical and thermal hypersensitivity, ongoing pain and anxio-depressive symptoms in mouse models of inflammatory and neuropathic pain without central side effects. Flow Induced Dispersion Analysis (FIDA) was used to characterize the peptide in solution and plasma — determining it self-assembles into micelles (critical micelle concentration ~12 µM, hydrodynamic radius ~30 Å) and measuring its binding to human serum albumin (KD 787 nM), indicating albumin binding is favored over micelle formation in plasma. It is an example of using FIDA to measure peptide self-assembly, size and binding affinity in solution.

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Peripherally restricted PICK1 inhibitor mPD5 ameliorates pain behaviors in murine inflammatory and neuropathic pain models
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