@article{todorov_calhoun_mccarty_sombers_2024, title={Electrochemical Quantification of Enkephalin Peptides Using Fast-Scan Cyclic Voltammetry}, volume={8}, ISSN={["1520-6882"]}, DOI={10.1021/acs.analchem.4c02418}, abstractNote={Endogenous opioid neuropeptides serve as important chemical signaling molecules in both the central and peripheral nervous systems, but there are few analytical tools for directly monitoring these molecules in situ. The opioid peptides share the amino acid motif, Tyr-Gly-Gly-Phe-, at the N-terminus. Met-enkephalin is a small opioid peptide comprised of only five amino acids with methionine (Met) incorporated at the C-terminus. Tyrosine (Tyr) and Met are electroactive, and their distinct electrochemical signatures can be utilized for quantitative molecular monitoring. This work encompasses a thorough voltammetric characterization of Tyr and Met redox chemistry as individual amino acids and when incorporated into small peptide fragments containing the shared Tyr-Gly-Gly-Phe- motif. NMR spectroscopy was used to determine the structure and conformation at near-physiological conditions. Voltammetric data demonstrate how the peak oxidation potential and the rate of electron transfer are dependent on the local chemical environment. Both the proximity of the electroactive residue to the C- or N-terminus and the hydrophobicity of the additional nonelectroactive amino acids profoundly affect sensitivity. Finally, the work uses the electrochemical signal for individual amino acids in a "training set", with a combination of principal component analysis and least-squares regression to accurately predict the voltammetric signal for short peptides comprising different combinations of those amino acids. Overall, this study demonstrates how fast-scan cyclic voltammetry can be utilized to discriminate between peptides with small differences in the chemical structure, thus establishing a framework for reliable quantification of small peptides in a complex signal, broadly speaking.}, journal={ANALYTICAL CHEMISTRY}, author={Todorov, Jovica and Calhoun, Sarah E. and Mccarty, Gregory S. and Sombers, Leslie A.}, year={2024}, month={Aug} }
 @article{calhoun_meunier_lee_mccarty_sombers_2018, title={Characterization of a Multiple-Scan-Rate Voltammetric Waveform for Real-Time Detection of Met-Enkephalin}, volume={10}, ISSN={1948-7193 1948-7193}, url={http://dx.doi.org/10.1021/acschemneuro.8b00351}, DOI={10.1021/acschemneuro.8b00351}, abstractNote={Opioid peptides are critically involved in a variety of physiological functions necessary for adaptation and survival, and as such, understanding the precise actions of endogenous opioid peptides will aid in identification of potential therapeutic strategies to treat a variety of disorders. However, few analytical tools are currently available that offer both the sensitivity and spatial resolution required to monitor peptidergic concentration fluctuations in situ on a time scale commensurate with that of neuronal communication. Our group has developed a multiple-scan-rate waveform to enable real-time voltammetric detection of tyrosine containing neuropeptides. Herein, we have evaluated the waveform parameters to increase sensitivity to methionine-enkephalin (M-ENK), an endogenous opioid neuropeptide implicated in pain, stress, and reward circuits. M-ENK dynamics were monitored in adrenal gland tissue, as well as in the dorsal striatum of anesthetized and freely behaving animals. The data reveal cofluctuations of catecholamine and M-ENK in both locations and provide measurements of M-ENK dynamics in the brain with subsecond temporal resolution. Importantly, this work also demonstrates how voltammetric waveforms can be customized to enhance detection of specific target analytes, broadly speaking.}, number={4}, journal={ACS Chemical Neuroscience}, publisher={American Chemical Society (ACS)}, author={Calhoun, S. E. and Meunier, C. J. and Lee, C. A. and McCarty, G. S. and Sombers, L. A.}, year={2018}, month={Dec}, pages={2022–2032} }