دورية أكاديمية
Structure-activity relationships of N-terminal variants of peptidomimetic tissue transglutaminase inhibitors.
| العنوان: | Structure-activity relationships of N-terminal variants of peptidomimetic tissue transglutaminase inhibitors. |
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| المؤلفون: | McNeil NMR; Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada., Gates EWJ; Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada., Firoozi N; Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada., Cundy NJ; Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada., Leccese J; Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada., Eisinga S; Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada., Tyndall JDA; School of Pharmacy, University of Otago, Dunedin, 9054, New Zealand., Adhikary G; Department of Biochemistry and Molecular Biology, and the Greenebaum Comprehensive Cancer Center, The University of Maryland School of Medicine, Baltimore, MD, 21021, USA., Eckert RL; Department of Biochemistry and Molecular Biology, and the Greenebaum Comprehensive Cancer Center, The University of Maryland School of Medicine, Baltimore, MD, 21021, USA., Keillor JW; Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada. Electronic address: jkeillor@uottawa.ca. |
| المصدر: | European journal of medicinal chemistry [Eur J Med Chem] 2022 Mar 15; Vol. 232, pp. 114172. Date of Electronic Publication: 2022 Feb 03. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Editions Scientifiques Elsevier Country of Publication: France NLM ID: 0420510 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1768-3254 (Electronic) Linking ISSN: 02235234 NLM ISO Abbreviation: Eur J Med Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Paris : Editions Scientifiques Elsevier Original Publication: Paris, S.E.C.T. [etc.] |
| مواضيع طبية MeSH: | Peptidomimetics*/pharmacology , Transglutaminases*/chemistry , Transglutaminases*/genetics , Transglutaminases*/metabolism, Enzyme Inhibitors/chemistry ; Protein Glutamine gamma Glutamyltransferase 2 ; Structure-Activity Relationship |
| مستخلص: | Tissue transglutaminase (TG2) is a multifunctional protein that catalyses protein crosslinking in the extracellular matrix, and functions as an intracellular G-protein. While both activities have been associated with human diseases, its role as a G-protein has been linked to cancer stem cell survival and maintenance of a metastatic phenotype. Recently we have shown that targeted covalent inhibitors (TCIs) can react selectively with the enzyme active site of TG2, to allosterically abolish its ability to bind GTP. In the present work, we focused on the variation of the N-terminal group of these peptidomimetic inhibitors, in order to enhance efficiency, while reducing log P and the number of rotatable bonds. This approach led to the synthesis and evaluation of 41 novel inhibitors, some of which had greatly improved efficiency and affinity for TG2 (e.g. TCI 72: K Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2022 Elsevier Masson SAS. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Acrylamide; Cancer; Irreversible inhibitors; Targeted covalent inhibitors; Tissue transglutaminase |
| المشرفين على المادة: | 0 (Enzyme Inhibitors) 0 (Peptidomimetics) EC 2.3.2.13 (Protein Glutamine gamma Glutamyltransferase 2) EC 2.3.2.13 (Transglutaminases) |
| تواريخ الأحداث: | Date Created: 20220214 Date Completed: 20220316 Latest Revision: 20220316 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1016/j.ejmech.2022.114172 |
| PMID: | 35158154 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1768-3254 |
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| DOI: | 10.1016/j.ejmech.2022.114172 |