2012 DEC 31 (NewsRx) -- By a News Reporter-Staff News Editor at AIDS Weekly -- Investigators publish new report on Opportunistic Infections. According to news reporting originating in Indianapolis, Indiana, by NewsRx journalists, research stated, "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."
The news reporters obtained a quote from the research, "Nature Medicine 17:822-829 (2011)]. 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 CBD3 peptide. This mutant peptide, conjugated to the cell penetrating motif of the HIV transduction domain protein TAT, exhibited greater anti-nociception in a rodent model of AIDS therapy-induced peripheral neuropathy when compared to the parent TAT-CBD3 peptide. Remarkably, intraperitoneal administration of TAT-CBD3A6K produced none of the minor side effects (i.e. tail kinking, body contortion) observed with the parent peptide. Interestingly, excitability of dissociated small diameter sensory neurons isolated from rats was also reduced by TAT-CBD3A6K peptide suggesting that suppression of excitability may be due to inhibition of T- and R-type Ca2+ channels. TAT-CBD3A6K had no effect on depolarization-evoked calcitonin gene related peptide (CGRP) release compared to vehicle control. Collectively, these results establish TAT-CBD3A6K as a peptide therapeutic with greater efficacy in an AIDS therapy-induced model of peripheral neuropathy than its parent peptide, TAT-CBD3."
According to the news reporters, the research concluded: "Structural modifications of the CBD3 scaffold peptide may result in peptides with selectivity against a particular subset of voltage-gated calcium channels resulting in a multipharmacology of action on the target."
For more information on this research see: CRMP-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. Molecular Pain, 2012;8():2-19. Molecular Pain can be contacted at: Biomed Central Ltd, 236 Grays Inn Rd, Floor 6, London WC1X 8HL, England. (BioMed Central - www.biomedcentral.com/; Molecular Pain - www.molecularpain.com)
Our news correspondents report that additional information may be obtained by contacting A.D. Piekarz, Sophia Therapeut LLC, Indianapolis, IN 46202, United States (see also Opportunistic Infections).
Keywords for this news article include: Peptides, Proteomics, Nociceptors, Indianapolis, Ion Channels, United States, Calcium Channels, Carrier Proteins, Membrane Proteins, Peripheral Neuropathy, Sensory Receptor Cells, Opportunistic Infections, North and Central America
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