<h3>Title</h3>
<p><span style="color: #0000ff;">Chemical tools for selective probing of protein activity and degradation of biomolecules</span></p>
<p><strong><span style="text-decoration: underline;">Abstract</span> :</strong></p>
<p style="text-align: justify;">Technological advancement often leads to major discoveries in chemical biology research. The functional diversity of biomolecules and their impact on vital biological processes inspire the development of methods for the precision engineering of these molecules. The growing interest in selective labeling and/or degradation of biomolecules has emerged from the necessity to understand and regulate their structure and function. During my talk, I will discuss how chemical tools can enable the selective tuning/degradation of biomolecules for their therapeutic applications. First, I will introduce a new electrophilic warhead to deliver the cysteine conjugates for protein therapeutics. Besides, the development of biorthogonal chemical reactions has been an unprecedented opportunity for the study and manipulation of biological processes within living systems. Precise perturbation of protein activity with high selectivity is crucial to probe and control dynamic protein activity. The development of proximity driven reversible covalent orthogonal strategy will enable the loss and gain of the function of protein with high selectivity to study dynamic cellular processes.</p>
<p style="text-align: justify;">Methods for target protein degradation have advanced the field of drug discovery. In particular, PROTACs and molecular glues gained much attention during the last decade. However, the PROTACs require strong affinity ligands for both E3 ligase and target protein whereas the discovery of most of the molecular glues was serendipitous. Hence, there is an unmet need to develop new technologies. A novel rational design of reversible covalently binding PROTACs (RECOBIN-PROTACs) will be discussed for target protein degradation. Also, another reversible/irreversible covalent strategy will introduce a new modality on PROTACs to generate a new class of Electrophilic-PROTACs that does not require the need of ligand for protein degradation. This new modality enhances the protein-protein interaction between E3 ligase and protein and it also stabilizes the ternary complex formation which plays a key role in the efficient degradation of the protein. Finally, targeted degradation of RNA species plays a key role in numerous cellular mechanisms. The specific interactions of enzyme with RNA gives an ample opportunity to develop small molecule degraders. So the principles of small molecule degraders that take advantage of specific enzyme-RNA interactions and modified bases on RNA to induce the degradation of specific RNA will be outlined.</p>