| 00:00:00 | Biophysical characterization of epigenetic interactions and associated drug discovery, using Isothermal Titration Calorimetry |
| 00:01:27 | Biophysical characterization of epigenetic interactions and associated drug discovery, using Isothermal Titration Calorimetry |
| 00:01:58 | Outline |
| 00:02:49 | What is epigenetics? |
| 00:03:47 | Epigenetics machinery |
| 00:06:05 | Chemical modifications “marks” of histone amino acids and nucleic acid bases |
| 00:06:47 | Epigenetic writers carry out modifications (marks) |
| 00:07:17 | Epigenetic readers recognize marks |
| 00:07:38 | Epigenetic erasers remove marks |
| 00:08:01 | Epigenetic proteins are druggable targets |
| 00:09:23 | Challenges of epigenetics protein research |
| 00:11:36 | Representative epigenetic proteins that contain bromodomain (BRD) module(s) |
| 00:12:54 | Importance of binding affinity to characterize epigenetic protein interactions |
| 00:14:44 | Binding and KD assays for epigenetics research and drug discovery |
| 00:17:30 | What is Isothermal Titration Calorimetry (ITC) |
| 00:19:02 | Basics of ITC |
| 00:23:34 | Beyond the binding affinity:ITC provides a total picture of binding energetics |
| 00:25:22 | ITC applications in life sciences research and epigenetics |
| 00:26:09 | Benefits of ITC for epigenetic interactions |
| 00:27:31 | ITC and epigenetics research |
| 00:28:40 | Epigenetic protein-cofactor interactions |
| 00:28:51 | A novel route to product specificity in the Suv4-20 family of histone H4K20 methyltransferases |
| 00:29:52 | ITC data binding between SAM and Suv4-20 proteins |
| 00:31:35 | Protein-protein interactions |
| 00:31:53 | Bromodomains |
| 00:32:32 | Histone Recognition and Large-ScaleStructural Analysis of the HumanBromodomain Family |
| 00:33:01 | Project included: |
| 00:34:14 | ITC for accurate KD determination – sample data |
| 00:36:07 | Role of the polycomb protein Eed in the propagation of repressive histone marks |
| 00:37:21 | Representative data: Validation of KD of EED binding to histone peptides by ITC |
| 00:38:36 | Protein-DNA interactions |
| 00:38:42 | Recognition and cleavage of 5-methylcytosine DNA by bacterial SRA-HNH proteins |
| 00:39:54 | ITC for KD of Sco5333 protein binding to fully- and hemi-methylated 54nt fragment |
| 00:41:43 | Beyond the binding affinity: thermodynamics and structural biology of protein-protein interactions |
| 00:41:58 | Chemical basis for the recognition oftrimethyllysine by epigenetic reader proteins |
| 00:43:10 | ITC: Comparison of binding of reader domains to histone 3 peptide analogs |
| 00:44:46 | Comparison of binding of reader domains to histone 3 peptide analogs - affinity |
| 00:45:45 | Comparison of binding of reader domains to histone 3 peptide analogs - enthalpy |
| 00:46:14 | Comparison of binding of reader domains to histone 3 peptide analogs - entropy |
| 00:47:30 | Small-Molecule Ligands of Methyl-Lysine Binding Proteins: Optimization of Selectivity for L3MBTL3 |
| 00:48:51 | Compound structures and binding to L3MBTL3 |
| 00:49:17 | Representative ITC data |
| 00:50:03 | Inhibitor selectivity for L3MBTL3 over L3MBTL1 with AlphaScreen and ITC |
| 00:51:34 | Benefits of ITC for epigenetic interactions |
| 00:52:35 | MicroCal PEAQ-ITC |
| 00:52:51 | MicroCal PEAQ-ITC: The new Gold Standard for binding affinity |
| 00:53:41 | Thank you |
| 00:53:51 | Thank you for your attentionAny questions? |
| 00:57:57 | Untitled |
| 00:58:18 | Untitled |
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.
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.