STIMULATION OF APOPTOSIS BY COMPUTATIONALLY DERIVED SMALL MOLECULES THAT BIND TO BCL-2
| Autor: | Cindy Fisher, Darryl Rideout, Kal Ramnarayan, Hengyi Zhu, Martha Mutomba, Sergei Mailiartchouk, Jing Wang, Christina Niemeyer, Seymour Mong, Thomas J. Brady |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
lcsh:T
Accession number (library science) lcsh:R Short Report Protein Data Bank (RCSB PDB) lcsh:Medicine Stimulation General Medicine Biology Ligand (biochemistry) lcsh:Technology Jurkat cells Small molecule General Biochemistry Genetics and Molecular Biology Cell biology Apoptosis Biophysics lcsh:Q lcsh:Science Intracellular General Environmental Science |
| Zdroj: | The Scientific World Journal The Scientific World Journal, Vol 1, Pp 107-107 (2001) |
| ISSN: | 1537-744X |
| DOI: | 10.1100/tsw.2001.23.124 |
| Popis: | METHODS. The NMR structure of Bcl-xL complexed with a portion of the BH3 region of its ligand Bak (PDB accession number 1BXL) (6) was used to generate a computational model of Bcl-2 complexed with a corresponding portion of its intracellular ligand Bax. The model was used in a 3-D computational search for non-peptide small molecules that disrupt Bcl-2/Bax interaction. Selected compounds were tested for their ability to inhibit binding of Eu 3+ -labelled Bax to Bcl-2 as measured by time-resolved fluorometry. Compounds with Ki values less than 50 µM were tested for their ability to induce apoptosis in Jurkat cells that overexpress Bcl-2 (Jurkat/Bcl-2 cells). The published Bcl-2 binding compound HA14-1 (7), was used as a control in the biochemical and cellular assays. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text