DPI-125 / Mount Cook Biosciences - LARVOL DELTA

Insights into Chemoreceptor MCP2201-Sensing D-Malate. (PubMed, Int J Mol Sci) - "Differences in attractant-bound LBD oligomerization, such as citrate-bound wildtype LBD monomer and D-malate-bound T105A dimer, indicated that LBD oligomerization is a consequence of signal transduction instead of a trigger. Our study expands our knowledge of chemoreceptor-sensing ligands and provides insight into the evolution of bacterial chemoreceptors."

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Attractant and repellent induce opposing changes in the four-helix bundle ligand-binding domain of a bacterial chemoreceptor. (PubMed, PLoS Biol) - "Here, we identified malate as a repellent recognized by the MCP2201 chemoreceptor in a bacterium Comamonas testosteroni and showed that it binds to the same site as an attractant citrate...We also observed opposing effects of repellent and attractant binding on the orientation of an alpha helix connecting the sensory domain to the transmembrane helix. We propose a model to illustrate how positive and negative signals might be generated."

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Effect of DPI-125 on opioid withdrawal behaviors in rats: a comparison study with methadone and buprenorphine (Neuroscience 2023) - "To assess the comparative effects of DPI-125 on withdrawal-like symptoms, 48 rats were implanted subcutaneously with 2 x 75mg morphine pellets to induce opioid dependence with pellets then removed 8 days later. 5mg/kg methadone treatment. These data suggest that DPI-125 might be a potentially useful MOUD to help improve outcomes in opioid use disorder."

Preclinical • Addiction (Opioid and Alcohol) • CNS Disorders • Depression • Pain • Psychiatry • Substance Abuse

The ligand-binding domain of a chemoreceptor from Comamonas testosteroni has a previously unknown homotrimeric structure. (PubMed, Mol Microbiol) - "Here, we report the structure of the periplasmic ligand-binding domain (LBD) of the transmembrane chemoreceptor MCP2201, which governs chemotaxis to citrate and other organic compounds in Comamonas testosteroni...This homotrimer was further confirmed with size-exclusion chromatography, analytical ultracentrifugation and cross-linking experiments. The physiological importance of the homotrimer for chemotaxis was demonstrated with site-directed mutations of key amino acid residues in C. testosteroni mutants."

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