記録された日時: April 26 2016

Duration: 58 minutes 43 seconds

The term ‘epigenetics’ refers to changes in and regulation of gene expression and function, without alteration of DNA sequence. The mechanisms behind these changes involve “epigenetic regulator” proteins that interact with and modify chromatin (DNA wrapped around histone proteins).

Epigenetic regulators and their interactions with histones or DNA are of growing interest to the life science research community, as they play an important role in many biological processes, and contribute to human diseases such as cancer and inflammation.

There are many current drug discovery projects looking for small molecules which can inhibit epigenetic regulators. This webinar will present an overview of how isothermal titration calorimetry (ITC) can be used to characterize the binding affinity and thermodynamics of epigenetic interactions, based on recent publications.

The presentation will also discuss how ITC is used to push forward small molecule drug discovery of epigenetic targets.
Table of contents
1. Biophysical characterization of epigenetic interactions and associated drug discovery, using Isothermal Titration Calorimetry
01:27
2. Biophysical characterization of epigenetic interactions and associated drug discovery, using Isothermal Titration Calorimetry
00:31
3. Outline
00:51
4. What is epigenetics?
00:58
5. Epigenetics machinery
02:18
6. Chemical modifications “marks” of histone amino acids and nucleic acid bases
00:42
7. Epigenetic writers carry out modifications (marks)
00:30
8. Epigenetic readers recognize marks
00:21
9. Epigenetic erasers remove marks
00:23
10. Epigenetic proteins are druggable targets
01:22
11. Challenges of epigenetics protein research
02:13
12. Representative epigenetic proteins that contain bromodomain (BRD) module(s)
01:18
13. Importance of binding affinity to characterize epigenetic protein interactions
01:50
14. Binding and KD assays for epigenetics research and drug discovery
02:46
15. What is Isothermal Titration Calorimetry (ITC)
01:32
16. Basics of ITC
04:32
17. Beyond the binding affinity:ITC provides a total picture of binding energetics
01:48
18. ITC applications in life sciences research and epigenetics
00:47
19. Benefits of ITC for epigenetic interactions
01:22
20. ITC and epigenetics research
01:09
21. Epigenetic protein-cofactor interactions
00:11
22. A novel route to product specificity in the Suv4-20 family of histone H4K20 methyltransferases
01:01
23. ITC data binding between SAM and Suv4-20 proteins
01:43
24. Protein-protein interactions
00:18
25. Bromodomains
00:39
26. Histone Recognition and Large-ScaleStructural Analysis of the HumanBromodomain Family
00:29
27. Project included:
01:13
28. ITC for accurate KD determination – sample data
01:53
29. Role of the polycomb protein Eed in the propagation of repressive histone marks
01:14
30. Representative data: Validation of KD of EED binding to histone peptides by ITC
01:15
31. Protein-DNA interactions
00:06
32. Recognition and cleavage of 5-methylcytosine DNA by bacterial SRA-HNH proteins
01:12
33. ITC for KD of Sco5333 protein binding to fully- and hemi-methylated 54nt fragment
01:49
34. Beyond the binding affinity: thermodynamics and structural biology of protein-protein interactions
00:15
35. Chemical basis for the recognition oftrimethyllysine by epigenetic reader proteins
01:12
36. ITC: Comparison of binding of reader domains to histone 3 peptide analogs
01:36
37. Comparison of binding of reader domains to histone 3 peptide analogs - affinity
00:59
38. Comparison of binding of reader domains to histone 3 peptide analogs - enthalpy
00:29
39. Comparison of binding of reader domains to histone 3 peptide analogs - entropy
01:16
40. Small-Molecule Ligands of Methyl-Lysine Binding Proteins: Optimization of Selectivity for L3MBTL3
01:21
41. Compound structures and binding to L3MBTL3
00:26
42. Representative ITC data
00:46
43. Inhibitor selectivity for L3MBTL3 over L3MBTL1 with AlphaScreen and ITC
01:31
44. Benefits of ITC for epigenetic interactions
01:01
45. MicroCal PEAQ-ITC
00:16
46. MicroCal PEAQ-ITC: The new Gold Standard for binding affinity
00:50
47. Thank you
00:10
48. Thank you for your attentionAny questions?
04:06
49. Untitled
00:21
50. Untitled
00:25