دورية أكاديمية
Broadening the Utility of Farnesyltransferase-Catalyzed Protein Labeling Using Norbornene-Tetrazine Click Chemistry.
| العنوان: | Broadening the Utility of Farnesyltransferase-Catalyzed Protein Labeling Using Norbornene-Tetrazine Click Chemistry. |
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| المؤلفون: | Auger SA; Department of Chemistry, University of Minnesota─Twin Cities, 207 Pleasant Street, Minneapolis, Minnesota 55455, United States., Venkatachalapathy S; Department of Chemistry, University of Minnesota─Twin Cities, 207 Pleasant Street, Minneapolis, Minnesota 55455, United States., Suazo KFG; Department of Chemistry, University of Minnesota─Twin Cities, 207 Pleasant Street, Minneapolis, Minnesota 55455, United States., Wang Y; Department of Chemistry, University of Minnesota─Twin Cities, 207 Pleasant Street, Minneapolis, Minnesota 55455, United States., Sarkis AW; Department of Chemistry, University of Minnesota─Twin Cities, 207 Pleasant Street, Minneapolis, Minnesota 55455, United States., Bernhagen K; Department of Chemistry, University of Minnesota─Twin Cities, 207 Pleasant Street, Minneapolis, Minnesota 55455, United States., Justyna K; Department of Chemistry, University of Minnesota─Twin Cities, 207 Pleasant Street, Minneapolis, Minnesota 55455, United States., Schaefer JV; Department of Biochemistry, University of Zurich, Zurich CH-8057, Switzerland., Wollack JW; Department of Chemistry and Biochemistry, St. Catherine University, 2004 Randolph Avenue, St. Paul, Minnesota 55105, United States., Plückthun A; Department of Biochemistry, University of Zurich, Zurich CH-8057, Switzerland., Li L; Department of Experimental and Clinical Pharmacology, University of Minnesota─Twin Cities, 2001 6th Street SE, Minneapolis, Minnesota 55455, United States., Distefano MD; Department of Chemistry, University of Minnesota─Twin Cities, 207 Pleasant Street, Minneapolis, Minnesota 55455, United States. |
| المصدر: | Bioconjugate chemistry [Bioconjug Chem] 2024 Jul 17; Vol. 35 (7), pp. 922-933. Date of Electronic Publication: 2024 Apr 24. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Chemical Society Country of Publication: United States NLM ID: 9010319 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-4812 (Electronic) Linking ISSN: 10431802 NLM ISO Abbreviation: Bioconjug Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : American Chemical Society, c1990- |
| مواضيع طبية MeSH: | Norbornanes*/chemistry , Click Chemistry* , Farnesyltranstransferase*/metabolism , Protein Prenylation*, Humans ; Animals |
| مستخلص: | Bioorthogonal chemistry has gained widespread use in the study of many biological systems of interest, including protein prenylation. Prenylation is a post-translational modification, in which one or two 15- or 20-carbon isoprenoid chains are transferred onto cysteine residues near the C-terminus of a target protein. The three main enzymes─protein farnesyltransferase (FTase), geranylgeranyl transferase I (GGTase I), and geranylgeranyl transferase II (GGTase II)─that catalyze this process have been shown to tolerate numerous structural modifications in the isoprenoid substrate. This feature has previously been exploited to transfer an array of farnesyl diphosphate analogues with a range of functionalities, including an alkyne-containing analogue for copper-catalyzed bioconjugation reactions. Reported here is the synthesis of an analogue of the isoprenoid substrate embedded with norbornene functionality (C10NorOPP) that can be used for an array of applications, ranging from metabolic labeling to selective protein modification. The probe was synthesized in seven steps with an overall yield of 7% and underwent an inverse electron demand Diels-Alder (IEDDA) reaction with tetrazine-containing tags, allowing for copper-free labeling of proteins. The use of C10NorOPP for the study of prenylation was explored in the metabolic labeling of prenylated proteins in HeLa, COS-7, and astrocyte cells. Furthermore, in HeLa cells, these modified prenylated proteins were identified and quantified using label-free quantification (LFQ) proteomics with 25 enriched prenylated proteins. Additionally, the unique chemistry of C10NorOPP was utilized for the construction of a multiprotein-polymer conjugate for the targeted labeling of cancer cells. That construct was prepared using a combination of norbornene-tetrazine conjugation and azide-alkyne cycloaddition, highlighting the utility of the additional degree of orthogonality for the facile assembly of new protein conjugates with novel structures and functions. |
| معلومات مُعتمدة: | RF1 AG056976 United States AG NIA NIH HHS |
| المشرفين على المادة: | 0 (Norbornanes) EC 2.5.1.29 (Farnesyltranstransferase) |
| تواريخ الأحداث: | Date Created: 20240424 Date Completed: 20240717 Latest Revision: 20240717 |
| رمز التحديث: | 20240717 |
| DOI: | 10.1021/acs.bioconjchem.4c00072 |
| PMID: | 38654427 |
| قاعدة البيانات: | MEDLINE |
Find this issue from the American Chemical Society | تدمد: | 1520-4812 |
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| DOI: | 10.1021/acs.bioconjchem.4c00072 |