A peptidomimetic modulator of the Ca_V2.2 N-type calcium channel for chronic pain.

ABSTRACT: Transmembrane Ca_v2.2 (N-type) voltage-gated calcium channels are genetically and pharmacologically validated, clinically relevant pain targets. Clinical block of Ca_v2.2 (e.g., with Prialt/Ziconotide) or indirect modulation [e.g., with gabapentinoids such as Gabapentin (GBP)] mitigates chronic pain but is encumbered by side effects and abuse liability. The cytosolic auxiliary subunit collapsin response mediator protein 2 (CRMP2) targets Ca_v2.2 to the sensory neuron membrane and regulates their function via an intrinsically disordered motif. A CRMP2-derived peptide (CBD3) uncouples the Ca_v2.2-CRMP2 interaction to inhibit calcium influx, transmitter release, and pain. We developed and applied a molecular dynamics approach to identify the A_1<

SUBMITTER: Gomez K 

PROVIDER: S-EPMC10666126 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature