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  • Based on our finding that TFA modulates GlyR function and

    2021-10-12

    Based on our finding that TFA modulates GlyR function and reports that TFA-bound pd0332991 synthesis can differ markedly from those synthesized without TFA, we retested a previously published dodecapeptide (D12-116) that also enhanced GlyR function but this time as a chloride salt (Tipps et al., 2010). No differences were seen in the abilities of the TFA-bound peptide or the chloride salt-bound peptide to enhance α1 GlyR function (Fig. 5), suggesting that the unknown amount of TFA present at a peptide concentration of 30μM was, in this case, too low to affect the glycine receptor. However, future studies will be required to evaluate the impact of these two peptide formulations in vivo.
    Conclusions The results of this study demonstrate that pd0332991 synthesis TFA, a major metabolite of fluorinated volatile anesthetics and a contaminant in synthesized peptides, acts as an allosteric modulator at the GlyR, but not at the closely-related GABAA or 5-HT3A receptors. The specificity of this effect is highly surprising, given that other GlyR modulators, such as ethanol, inhaled anesthetics and metals such as zinc, do not show this degree of specificity. Our studies also suggest that TFA contamination in HPLC-purified peptides is potentially an important source of experimental variability or error that requires control in vitro and may have unexpected effects when peptide drugs are administered in vivo.
    Acknowledgements This research was supported by National Institute on Alcohol Abuse & Alcoholism grant R03 AA018197.