biostudies-literaturePiekarz ADNCRR NIH HHSNIDA NIH HHSNINDS NIH HHS54https://www.ebi.ac.uk/biostudies/studies/S-EPMC3502107biostudies-literatureUnknown8<h4>Background</h4>The ubiquity of protein-protein interactions in biological signaling offers ample opportunities for therapeutic intervention. We previously identified a peptide, designated CBD3, that suppressed inflammatory and neuropathic behavioral hypersensitivity in rodents by inhibiting the ability of collapsin response mediator protein 2 (CRMP-2) to bind to N-type voltage-activated calcium channels (CaV2.2) [Brittain et al. Nature Medicine 17:822-829 (2011)].<h4>Results and discussion</h4>Here, we utilized SPOTScan analysis to identify an optimized variation of the CBD3 peptide (CBD3A6K) that bound with greater affinity to Ca²⁺ channels. Molecular dynamics simulations demonstrated that the CBD3A6K peptide was more stable and less prone to the unfolding observed with the parent CBDMolecular painCRMP-2 peptide mediated decrease of high and low voltage-activated calcium channels, attenuation of nociceptor excitability, and anti-nociception in a model of AIDS therapy-induced painful peripheral neuropathy.PMC3502107R01 NS049136NS049136-06DA026040-04RR025761Piekarz ADWang BWang RRipsch MSKhanna RDue MRVasko MRKhanna MWhite FAMeroueh SOfalseCRMP-2 peptide mediated decrease of high and low voltage-activated calcium channels, attenuation of nociceptor excitability, and anti-nociception in a model of AIDS therapy-induced painful peripheral neuropathy.<h4>Background</h4>The ubiquity of protein-protein interactions in biological signaling offers ample opportunities for therapeutic intervention. We previously identified a peptide, designated CBD3, that suppressed inflammatory and neuropathic behavioral hypersensitivity in rodents by inhibiting the ability of collapsin response mediator protein 2 (CRMP-2) to bind to N-type voltage-activated calcium channels (CaV2.2) [Brittain et al. Nature Medicine 17:822-829 (2011)].<h4>Results and discussion</h4>Here, we utilized SPOTScan analysis to identify an optimized variation of the CBD3 peptide (CBD3A6K) that bound with greater affinity to Ca²⁺ channels. Molecular dynamics simulations demonstrated that the CBD3A6K peptide was more stable and less prone to the unfolding observed with the parent CBD2012-01-01T00:00:00Z2012 Jul2026-04-07T20:46:14.688Z2026-04-07T17:47:08.12ZS-EPMC35021072282836910.1186/1744-8069-8-54