التفاصيل البيبلوغرافية
| العنوان: |
Activity-Based Hydrazine Probes for Protein Profiling of Electrophilic Functionality in Therapeutic Targets |
| المؤلفون: |
Zongtao Lin (754056), Xie Wang (739483), Katelyn A. Bustin (11303009), Kyosuke Shishikura (11303012), Nate R. McKnight (11303015), Lin He (102807), Radu M. Suciu (3184680), Kai Hu (311882), Xian Han (8812265), Mina Ahmadi (14980), Erika J. Olson (11303018), William H. Parsons (1875712), Megan L. Matthews (2232757) |
| سنة النشر: |
2021 |
| المجموعة: |
Smithsonian Institution: Digital Repository |
| مصطلحات موضوعية: |
Biochemistry, Medicine, Genetics, Pharmacology, Evolutionary Biology, Environmental Sciences not elsewhere classified, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, reactivity underpins function, probe attachment occurs, pharmacologically important classes, nucleophilic amino acid, less charted hemisphere, labile regulatory modifications, identify specific inhibitors, electrophilic enzyme cofactors, multiple enzyme classes, based protein profiling, use electrophilic groups, based hydrazine probes, protein profiling, electrophilic functionality, rich hydrazine, inorganic cofactors, identify cases, versatile class, transient intermediates, therapeutic targets, single type, radicaloid mechanisms |
| الوصف: |
Most known probes for activity-based protein profiling (ABPP) use electrophilic groups that tag a single type of nucleophilic amino acid to identify cases in which its hyper-reactivity underpins function. Much important biochemistry derives from electrophilic enzyme cofactors, transient intermediates, and labile regulatory modifications, but ABPP probes for such species are underdeveloped. Here, we describe a versatile class of probes for this less charted hemisphere of the proteome. The use of an electron-rich hydrazine as the common chemical modifier enables covalent targeting of multiple, pharmacologically important classes of enzymes bearing diverse organic and inorganic cofactors. Probe attachment occurs by both polar and radicaloid mechanisms, can be blocked by molecules that occupy the active sites, and depends on the proper poise of the active site for turnover. These traits will enable the probes to be used to identify specific inhibitors of individual members of these multiple enzyme classes, making them uniquely versatile among known ABPP probes. |
| نوع الوثيقة: |
dataset |
| اللغة: |
unknown |
| Relation: |
https://figshare.com/articles/dataset/Activity-Based_Hydrazine_Probes_for_Protein_Profiling_of_Electrophilic_Functionality_in_Therapeutic_Targets/15505921 |
| DOI: |
10.1021/acscentsci.1c00616.s002 |
| الاتاحة: |
https://doi.org/10.1021/acscentsci.1c00616.s002 |
| Rights: |
CC BY-NC 4.0 |
| رقم الانضمام: |
edsbas.D3DBA5FB |
| قاعدة البيانات: |
BASE |