Methods and compositions for inhibition of BCL6 repression
View Patent ↗Provided are peptides or mimetics that block corepressor binding to a BCL6 lateral groove. Also provided are methods or blocking corepressor binding to the BCL6 lateral groove. Additionally, methods of inhibiting BCL6 repression in a mammalian cell, and methods of treating a mammal with cancer are provided.
1. A method of determining whether a test compound inhibits corepressor binding to B-cell lymphoma 6 (BCL6), the method comprising determining whether the test compound binds to both BTB domains of a BCL-6 BTB dimer, and identifying the test compound as an inhibitor or not of corepressor binding to BCL6, wherein a compound that binds to both BTB domains of a BCL-6 BTB dimer is an inhibitor of corepressor binding to BCL6 and wherein each BTB domain comprises the amino acid sequence set forth in SEQ ID NO:11 or SEQ ID NO:12.
2. The method of claim 1 , wherein the test compound is an organic compound less than 1000 molecular weight.
3. The method of claim 1 , wherein the test compound is an organic compound less than 3000 molecular weight.
4. The method of claim 1 , wherein the test compound is an aptamer.
5. The method of claim 1 , wherein the test compound is a peptide or peptide mimetic.
6. The method of claim 5 , wherein the peptide or mimetic comprises SEQ ID NO:10.
7. The method of claim 5 , wherein the peptide or mimetic comprises SEQ ID NO:1.
8. The method of claim 5 , wherein the peptide or mimetic comprises SEQ ID NO:2.
9. The method of claim 5 , wherein the peptide or mimetic comprises SEQ ID NO:3.
10. The method of claim 1 , wherein the BCL-6 BTB dimer is part of a BCL-6 homodimer.
11. The method of claim 1 , wherein the compound binds to a B1′and to a α1′of a first BTB domain of the BCL6 BTB dimer and to an α2 and to an α3 and to an α6 of a second BTB domain of the BCL6 BTB dimer.
12. The method of claim 1 , wherein the test compound binds to an asparagine residue position 21 of SEQ ID NO: 11.
13. The method of claim 1 , wherein the test compound binds to a histidine at residue position 116 of SEQ ID NO: 11.
14. The method of claim 1 , wherein determining whether the test compound binds to both BTB domains of a BCL-6 BTB dimer is effected using X-ray crystallography.