دورية أكاديمية
Novel irreversible peptidic inhibitors of transglutaminase 2.
| العنوان: | Novel irreversible peptidic inhibitors of transglutaminase 2. |
|---|---|
| المؤلفون: | Cundy NJ; Department of Chemistry and Biomolecular Sciences, University of Ottawa Ottawa Ontario K1N 6N5 Canada jkeillor@uottawa.ca., Arciszewski J; Department of Chemistry and Biomolecular Sciences, University of Ottawa Ottawa Ontario K1N 6N5 Canada jkeillor@uottawa.ca., Gates EWJ; Department of Chemistry and Biomolecular Sciences, University of Ottawa Ottawa Ontario K1N 6N5 Canada jkeillor@uottawa.ca., Acton SL; Department of Chemistry and Biomolecular Sciences, University of Ottawa Ottawa Ontario K1N 6N5 Canada jkeillor@uottawa.ca., Passley KD; Department of Chemistry and Biomolecular Sciences, University of Ottawa Ottawa Ontario K1N 6N5 Canada jkeillor@uottawa.ca., Awoonor-Williams E; Department of Chemistry and Biomolecular Sciences, University of Ottawa Ottawa Ontario K1N 6N5 Canada jkeillor@uottawa.ca., Boyd EK; Department of Chemistry and Biomolecular Sciences, University of Ottawa Ottawa Ontario K1N 6N5 Canada jkeillor@uottawa.ca., Xu N; Department of Chemistry and Biomolecular Sciences, University of Ottawa Ottawa Ontario K1N 6N5 Canada jkeillor@uottawa.ca., Pierson É; Department of Chemistry and Biomolecular Sciences, University of Ottawa Ottawa Ontario K1N 6N5 Canada jkeillor@uottawa.ca., Fernandez-Ansieta C; Department of Chemistry and Biomolecular Sciences, University of Ottawa Ottawa Ontario K1N 6N5 Canada jkeillor@uottawa.ca., Albert MR; Department of Chemistry and Biomolecular Sciences, University of Ottawa Ottawa Ontario K1N 6N5 Canada jkeillor@uottawa.ca., McNeil NMR; Department of Chemistry and Biomolecular Sciences, University of Ottawa Ottawa Ontario K1N 6N5 Canada jkeillor@uottawa.ca., Adhikary G; Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine Baltimore Maryland 21201 USA., Eckert RL; Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine Baltimore Maryland 21201 USA., Keillor JW; Department of Chemistry and Biomolecular Sciences, University of Ottawa Ottawa Ontario K1N 6N5 Canada jkeillor@uottawa.ca. |
| المصدر: | RSC medicinal chemistry [RSC Med Chem] 2022 Dec 28; Vol. 14 (2), pp. 378-385. Date of Electronic Publication: 2022 Dec 28 (Print Publication: 2023). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Royal Society of Chemistry Country of Publication: England NLM ID: 101759460 Publication Model: eCollection Cited Medium: Internet ISSN: 2632-8682 (Electronic) Linking ISSN: 26328682 NLM ISO Abbreviation: RSC Med Chem Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: Cambridge : Royal Society of Chemistry, [2020]- |
| مستخلص: | Transglutaminase 2 (TG2), also referred to as tissue transglutaminase, plays crucial roles in both protein crosslinking and cell signalling. It is capable of both catalysing transamidation and acting as a G-protein, these activities being conformation-dependent, mutually exclusive, and tightly regulated. The dysregulation of both activities has been implicated in numerous pathologies. TG2 is expressed ubiquitously in humans and is localized both intracellularly and extracellularly. Targeted TG2 therapies have been developed but have faced numerous hurdles including decreased efficacy in vivo . Our latest efforts in inhibitor optimization involve the modification of a previous lead compound's scaffold by insertion of various amino acid residues into the peptidomimetic backbone, and derivatization of the N -terminus with substituted phenylacetic acids, resulting in 28 novel irreversible inhibitors. These inhibitors were evaluated for their ability to inhibit TG2 in vitro and their pharmacokinetic properties, and the most promising candidate 35 ( k Competing Interests: There are no conflicts to declare. (This journal is © The Royal Society of Chemistry.) |
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| تواريخ الأحداث: | Date Created: 20230227 Latest Revision: 20231229 |
| رمز التحديث: | 20231229 |
| مُعرف محوري في PubMed: | PMC9945859 |
| DOI: | 10.1039/d2md00417h |
| PMID: | 36846375 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2632-8682 |
|---|---|
| DOI: | 10.1039/d2md00417h |