Activity probe for in vivo profiling of the specificity of proteasome inhibitor bortezomib.
Proteasome inhibitors, such as the dipeptide boronic acid bortezomib, are emerging as important tools in the treatment of the fatal hematologic malignancy multiple myeloma. Despite the recent US Food and Drug Administration approval of bortezomib (PS341, Velcade) for the treatment of refractory mult...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2005
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| _version_ | 1826276798658248704 |
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| author | Berkers, C Verdoes, M Lichtman, E Fiebiger, E Kessler, B Anderson, K Ploegh, H Ovaa, H Galardy, P |
| author_facet | Berkers, C Verdoes, M Lichtman, E Fiebiger, E Kessler, B Anderson, K Ploegh, H Ovaa, H Galardy, P |
| author_sort | Berkers, C |
| collection | OXFORD |
| description | Proteasome inhibitors, such as the dipeptide boronic acid bortezomib, are emerging as important tools in the treatment of the fatal hematologic malignancy multiple myeloma. Despite the recent US Food and Drug Administration approval of bortezomib (PS341, Velcade) for the treatment of refractory multiple myeloma, many of the basic pharmacologic parameters of bortezomib and its mode of action on myeloma cells remain to be determined. We describe the synthesis and use of a cell-permeant active site-directed probe, which allows profiling of proteasomal activities in living cells. When we compared proteasome activity patterns in cultured cells and crude cell extracts with this probe, we observed substantial differences, stressing the importance for bioassays compatible with live cells to ensure accuracy of such measurements. Using this probe, we investigated the in vivo subunit specificities of bortezomib and another inhibitor, MG132. |
| first_indexed | 2024-03-06T23:19:16Z |
| format | Journal article |
| id | oxford-uuid:682f406a-f96d-4878-8fee-48ea7b2cbe2f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:19:16Z |
| publishDate | 2005 |
| record_format | dspace |
| spelling | oxford-uuid:682f406a-f96d-4878-8fee-48ea7b2cbe2f2022-03-26T18:43:17ZActivity probe for in vivo profiling of the specificity of proteasome inhibitor bortezomib.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:682f406a-f96d-4878-8fee-48ea7b2cbe2fEnglishSymplectic Elements at Oxford2005Berkers, CVerdoes, MLichtman, EFiebiger, EKessler, BAnderson, KPloegh, HOvaa, HGalardy, PProteasome inhibitors, such as the dipeptide boronic acid bortezomib, are emerging as important tools in the treatment of the fatal hematologic malignancy multiple myeloma. Despite the recent US Food and Drug Administration approval of bortezomib (PS341, Velcade) for the treatment of refractory multiple myeloma, many of the basic pharmacologic parameters of bortezomib and its mode of action on myeloma cells remain to be determined. We describe the synthesis and use of a cell-permeant active site-directed probe, which allows profiling of proteasomal activities in living cells. When we compared proteasome activity patterns in cultured cells and crude cell extracts with this probe, we observed substantial differences, stressing the importance for bioassays compatible with live cells to ensure accuracy of such measurements. Using this probe, we investigated the in vivo subunit specificities of bortezomib and another inhibitor, MG132. |
| spellingShingle | Berkers, C Verdoes, M Lichtman, E Fiebiger, E Kessler, B Anderson, K Ploegh, H Ovaa, H Galardy, P Activity probe for in vivo profiling of the specificity of proteasome inhibitor bortezomib. |
| title | Activity probe for in vivo profiling of the specificity of proteasome inhibitor bortezomib. |
| title_full | Activity probe for in vivo profiling of the specificity of proteasome inhibitor bortezomib. |
| title_fullStr | Activity probe for in vivo profiling of the specificity of proteasome inhibitor bortezomib. |
| title_full_unstemmed | Activity probe for in vivo profiling of the specificity of proteasome inhibitor bortezomib. |
| title_short | Activity probe for in vivo profiling of the specificity of proteasome inhibitor bortezomib. |
| title_sort | activity probe for in vivo profiling of the specificity of proteasome inhibitor bortezomib |
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