A5000905384- Protein Degradation and Inhibitors
- Ubiquitin and proteasome pathways
- Click Chemistry and Applications
- Multiple Myeloma Research and Treatments
- Computational Drug Discovery Methods
- Chemical Synthesis and Analysis
- Chronic Lymphocytic Leukemia Research
- Urban Agriculture and Sustainability
- Plant-Microbe Interactions and Immunity
- Climate change impacts on agriculture
Massachusetts Institute of Technology
2024
University of California, Berkeley
2020-2022
Innovative Genomics Institute
2022
Novartis (Switzerland)
2020
Proteolysis-targeting chimeras (PROTACs), heterobifunctional compounds that consist of protein-targeting ligands linked to an E3 ligase recruiter, have arisen as a powerful therapeutic modality for targeted protein degradation (TPD). Despite the popularity TPD approaches in drug discovery, only small number recruiters are available >600 ligases exist human cells. Here, we discovered cysteine-reactive covalent ligand, EN106, targets FEM1B, recently critical component cellular response...
Targeted protein degradation (TPD) and proteolysis-targeting chimeras (PROTACs) have arisen as powerful therapeutic modalities for degrading specific proteins in a proteasome-dependent manner. However, major limitation of TPD is the lack E3 ligase recruiters. Recently, we discovered natural product nimbolide covalent recruiter RNF114. Here, show broader utility an applications. We demonstrate that PROTAC linking to kinase BCR-ABL fusion oncogene inhibitor dasatinib, BT1, selectively degrades...
As a traceless, bioreversible modification, the esterification of carboxyl groups in peptides and proteins has potential to increase their clinical utility. An impediment is lack strategies quantify esterase-catalyzed hydrolysis rates for esters esterified biologics. We have developed continuous Förster resonance energy transfer (FRET) assay esterase activity based on peptidic substrate protease, Glu-C, that cleaves glutamyl peptide bond only if side chain free acid. Using pig liver (PLE)...
Abstract Targeted protein degradation (TPD) and proteolysis-targeting chimeras (PROTACs) have arisen as powerful therapeutic modalities for degrading specific targets in a proteasome-dependent manner. However, major limitation to broader TPD applications is the lack of E3 ligase recruiters. Recently, we discovered natural product nimbolide covalent ligand RNF114. When linked BET family inhibitor JQ1, resulting heterobifunctional PROTAC molecule was capable selectively BRD4 cancer cells....
Author(s): Awasthi, Shevya; Das, Doyel; Harari, Emily; Krishnapura, Ananya; Zhang, Erika; Lee, Rosa | Abstract: Interview with Dr. Peggy Lemaux