Synthesis of a Hydrogen Isotope-Labeled SGLT1 <i>C</i>-Glucoside Ligand for Distribution and Metabolic Fate Studies
Over the last decades, a novel immunological function was established for the sodium–glucose co-transporter 1 (SGLT1), a protein involved in sugar absorption in the small intestine. High-glucose dosage and pharmacological concentrations of a <i>C</i>-glucoside analog showed a protective...
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2025-03-01
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| author | Giuseppe D’Orazio Barbara La Ferla |
| author_facet | Giuseppe D’Orazio Barbara La Ferla |
| author_sort | Giuseppe D’Orazio |
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| description | Over the last decades, a novel immunological function was established for the sodium–glucose co-transporter 1 (SGLT1), a protein involved in sugar absorption in the small intestine. High-glucose dosage and pharmacological concentrations of a <i>C</i>-glucoside analog showed a protective role in in vitro and in vivo models of severe inflammation states; experimental evidence suggests the engagement of SGLT1 in these processes. The mechanism of action underlying the protection is still unclear. To enhance our understanding of the molecular mechanisms responsible for this protection, we have developed a synthesis for the preparation of hydrogen isotope-labeled versions of the <i>C</i>-glucoside hit compound. Specifically, we report the synthesis of the deuterium-labeled derivative, which can be utilized for mass spectrometry-based research to examine the compound’s metabolic pathway, distribution, and cellular/tissue localization. The synthetic method developed can be extended to produce the tritiated analog, serving as a radioactive tracer. |
| format | Article |
| id | doaj-art-df1a8223637e4f60bcc41fc79f5d8707 |
| institution | DOAJ |
| issn | 1422-8599 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molbank |
| spelling | doaj-art-df1a8223637e4f60bcc41fc79f5d87072025-08-20T02:42:22ZengMDPI AGMolbank1422-85992025-03-0120251M198210.3390/M1982Synthesis of a Hydrogen Isotope-Labeled SGLT1 <i>C</i>-Glucoside Ligand for Distribution and Metabolic Fate StudiesGiuseppe D’Orazio0Barbara La Ferla1Department of Chemistry, Università degli Studi di Milano, Via C. Golgi 19, 20133 Milan, ItalyDepartment of Earth and Environmental Sciences DISAT, Università degli Studi di Milano-Bicocca, Piazza della Scienza 1, 20126 Milan, ItalyOver the last decades, a novel immunological function was established for the sodium–glucose co-transporter 1 (SGLT1), a protein involved in sugar absorption in the small intestine. High-glucose dosage and pharmacological concentrations of a <i>C</i>-glucoside analog showed a protective role in in vitro and in vivo models of severe inflammation states; experimental evidence suggests the engagement of SGLT1 in these processes. The mechanism of action underlying the protection is still unclear. To enhance our understanding of the molecular mechanisms responsible for this protection, we have developed a synthesis for the preparation of hydrogen isotope-labeled versions of the <i>C</i>-glucoside hit compound. Specifically, we report the synthesis of the deuterium-labeled derivative, which can be utilized for mass spectrometry-based research to examine the compound’s metabolic pathway, distribution, and cellular/tissue localization. The synthetic method developed can be extended to produce the tritiated analog, serving as a radioactive tracer.https://www.mdpi.com/1422-8599/2025/1/M1982sodium–glucose co-transporter 1<i>C</i>-glycosidesglycomimeticshydrogen Isotopesdeuterium labelingtritium labeling |
| spellingShingle | Giuseppe D’Orazio Barbara La Ferla Synthesis of a Hydrogen Isotope-Labeled SGLT1 <i>C</i>-Glucoside Ligand for Distribution and Metabolic Fate Studies Molbank sodium–glucose co-transporter 1 <i>C</i>-glycosides glycomimetics hydrogen Isotopes deuterium labeling tritium labeling |
| title | Synthesis of a Hydrogen Isotope-Labeled SGLT1 <i>C</i>-Glucoside Ligand for Distribution and Metabolic Fate Studies |
| title_full | Synthesis of a Hydrogen Isotope-Labeled SGLT1 <i>C</i>-Glucoside Ligand for Distribution and Metabolic Fate Studies |
| title_fullStr | Synthesis of a Hydrogen Isotope-Labeled SGLT1 <i>C</i>-Glucoside Ligand for Distribution and Metabolic Fate Studies |
| title_full_unstemmed | Synthesis of a Hydrogen Isotope-Labeled SGLT1 <i>C</i>-Glucoside Ligand for Distribution and Metabolic Fate Studies |
| title_short | Synthesis of a Hydrogen Isotope-Labeled SGLT1 <i>C</i>-Glucoside Ligand for Distribution and Metabolic Fate Studies |
| title_sort | synthesis of a hydrogen isotope labeled sglt1 i c i glucoside ligand for distribution and metabolic fate studies |
| topic | sodium–glucose co-transporter 1 <i>C</i>-glycosides glycomimetics hydrogen Isotopes deuterium labeling tritium labeling |
| url | https://www.mdpi.com/1422-8599/2025/1/M1982 |
| work_keys_str_mv | AT giuseppedorazio synthesisofahydrogenisotopelabeledsglt1iciglucosideligandfordistributionandmetabolicfatestudies AT barbaralaferla synthesisofahydrogenisotopelabeledsglt1iciglucosideligandfordistributionandmetabolicfatestudies |