Inhibiting S100B(ββ) for activating wild-type p53 : design of stapled peptides
S100B(ββ) is a member of the S100B protein family and is distributed in a cell-specific manner. Its levels are elevated in several cancers such as malignant melanoma and correlate directly with poor prognosis in patients. S100B(ββ) directly interacts with the tumor suppressor p53, inhibiting tetrame...
| Main Authors: | , , , |
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| Format: | Journal Article |
| Language: | English |
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2020
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| Online Access: | https://hdl.handle.net/10356/137422 |
| _version_ | 1826110045608214528 |
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| author | Kannan, Srinivasaraghavan Aronica, Pietro G. A. Tan, Yaw Sing Verma, Chandra Shekhar |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Kannan, Srinivasaraghavan Aronica, Pietro G. A. Tan, Yaw Sing Verma, Chandra Shekhar |
| author_sort | Kannan, Srinivasaraghavan |
| collection | NTU |
| description | S100B(ββ) is a member of the S100B protein family and is distributed in a cell-specific manner. Its levels are elevated in several cancers such as malignant melanoma and correlate directly with poor prognosis in patients. S100B(ββ) directly interacts with the tumor suppressor p53, inhibiting tetramerization and protein kinase C-dependent phosphorylation, consequently decreasing p53 DNA binding and transcriptional activity, and preventing apoptosis. Thus, S100B(ββ) is being pursued as a target for therapeutic inhibition. However, development of small molecule inhibitors targeting p53-interactions has met with limited success. In this work, we present a set of designed stapled peptide inhibitors of S100B(ββ), guided by the structure of the C-terminal domain of p53 complexed with S100B(ββ). We further modified a tightly binding stapled peptide with imaging agents and propose these as potential diagnostic agents to detect S100B(ββ) as a biomarker. |
| first_indexed | 2024-10-01T02:28:03Z |
| format | Journal Article |
| id | ntu-10356/137422 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T02:28:03Z |
| publishDate | 2020 |
| record_format | dspace |
| spelling | ntu-10356/1374222023-02-28T16:57:30Z Inhibiting S100B(ββ) for activating wild-type p53 : design of stapled peptides Kannan, Srinivasaraghavan Aronica, Pietro G. A. Tan, Yaw Sing Verma, Chandra Shekhar School of Biological Sciences Science::Biological sciences S100B Protein Cancer S100B(ββ) is a member of the S100B protein family and is distributed in a cell-specific manner. Its levels are elevated in several cancers such as malignant melanoma and correlate directly with poor prognosis in patients. S100B(ββ) directly interacts with the tumor suppressor p53, inhibiting tetramerization and protein kinase C-dependent phosphorylation, consequently decreasing p53 DNA binding and transcriptional activity, and preventing apoptosis. Thus, S100B(ββ) is being pursued as a target for therapeutic inhibition. However, development of small molecule inhibitors targeting p53-interactions has met with limited success. In this work, we present a set of designed stapled peptide inhibitors of S100B(ββ), guided by the structure of the C-terminal domain of p53 complexed with S100B(ββ). We further modified a tightly binding stapled peptide with imaging agents and propose these as potential diagnostic agents to detect S100B(ββ) as a biomarker. NRF (Natl Research Foundation, S’pore) ASTAR (Agency for Sci., Tech. and Research, S’pore) EDB (Economic Devt. Board, S’pore) Published version 2020-03-25T03:54:02Z 2020-03-25T03:54:02Z 2019 Journal Article Kannan, S., Aronica, P. G. A., Tan, Y. S., & Verma, C. S. (2019). Inhibiting S100B(ββ) for activating wild-type p53 : design of stapled peptides. ACS Omega, 4(3), 5335-5344. doi:10.1021/acsomega.9b00097 2470-1343 https://hdl.handle.net/10356/137422 10.1021/acsomega.9b00097 2-s2.0-85062880662 3 4 5335 5344 en ACS Omega © 2019 American Chemical Society. This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes. application/pdf |
| spellingShingle | Science::Biological sciences S100B Protein Cancer Kannan, Srinivasaraghavan Aronica, Pietro G. A. Tan, Yaw Sing Verma, Chandra Shekhar Inhibiting S100B(ββ) for activating wild-type p53 : design of stapled peptides |
| title | Inhibiting S100B(ββ) for activating wild-type p53 : design of stapled peptides |
| title_full | Inhibiting S100B(ββ) for activating wild-type p53 : design of stapled peptides |
| title_fullStr | Inhibiting S100B(ββ) for activating wild-type p53 : design of stapled peptides |
| title_full_unstemmed | Inhibiting S100B(ββ) for activating wild-type p53 : design of stapled peptides |
| title_short | Inhibiting S100B(ββ) for activating wild-type p53 : design of stapled peptides |
| title_sort | inhibiting s100b ββ for activating wild type p53 design of stapled peptides |
| topic | Science::Biological sciences S100B Protein Cancer |
| url | https://hdl.handle.net/10356/137422 |
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