Synthesis and Characterization of Furoxan Incorporating Photoaffinity Labeling Probes

Abstract

Event Abstract Back to Event Synthesis and Characterization of Furoxan Incorporating Photoaffinity Labeling Probes Ethel N. Tackie-Yarboi1*, Anvitha R. Madhavaram1* and Isaac Schiefer1* 1 University of Toledo, United States Nitric oxide (NO) plays a critical role in neuronal function and synaptic plasticity. Molecules capable of enhancing NO signaling have shown promise as potential therapeutics for neurodegenerative disorders. We are engaged in the development of a novel class of NO mimetics known as furoxans (1,2,5 oxadiazole-N-oxides). Furoxans are commonly described as thiol-dependent NO mimetics, which must react with biological thiols to exhibit NO bioactivity. We have created a series of attenuated furoxans, which do not readily react with generic cellular thiols, such as glutathione or L-cysteine. Nevertheless, our furoxans display neuroprotection in cell culture and the ability to reverse scopolamine induced cognition deficits in a model of contextual fear memory. We have demonstrated that furoxan neuroprotection is reversed upon blockade of NO/sGC (soluble guanylyl cyclase) signaling. We hypothesize our attenuated furoxans react with a subset of yet to be identified relatively reactive protein thiols. The work presented focuses on the synthesis and characterization of novel furoxan probes containing, 1) a photoaffinity labeling group, either a diazirine or perfluoroarylazide, for transient covalent modification of interacting proteins; and 2) a terminal alkyne for conjugation with a fluorophore and subsequent visualization of protein modification by SDS-PAGE, to elucidate this hypothesis. We have observed distinct advantages and disadvantages of each photoaffinity labeling moiety with regards to stability and rate of photolysis. Efforts are ongoing to identify furoxan target proteins in primary cell culture. Keywords: Furoxan, Neuroprotection, Nitric Oxide, Photoaffimty labelling, PROBES Conference: National Organization for the Professional Advancement of Black Chemists and Chemical Engineers (NOBCChE) 45th Annual Conference , Orlando, Florida, United States, 17 Sep - 20 Sep, 2018. Presentation Type: Oral Presentation Topic: Medicinal Chemistry Citation: Tackie-Yarboi EN, Madhavaram AR and Schiefer I (2019). Synthesis and Characterization of Furoxan Incorporating Photoaffinity Labeling Probes. Front. Chem. Conference Abstract: National Organization for the Professional Advancement of Black Chemists and Chemical Engineers (NOBCChE) 45th Annual Conference . doi: 10.3389/conf.fchem.2018.01.00013 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 08 Oct 2018; Published Online: 17 Jan 2019. * Correspondence: Ms. Ethel N Tackie-Yarboi, University of Toledo, Toledo, United States, Ethel.Tackie-Yarboi@rockets.utoledo.edu Ms. Anvitha R Madhavaram, University of Toledo, Toledo, United States, anvitha.madhavaram@rockets.utoledo.edu Dr. Isaac Schiefer, University of Toledo, Toledo, United States, isaac.schiefer@utoledo.edu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Ethel N Tackie-Yarboi Anvitha R Madhavaram Isaac Schiefer Google Ethel N Tackie-Yarboi Anvitha R Madhavaram Isaac Schiefer Google Scholar Ethel N Tackie-Yarboi Anvitha R Madhavaram Isaac Schiefer PubMed Ethel N Tackie-Yarboi Anvitha R Madhavaram Isaac Schiefer Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.