Departmental webinar on "Organic chemistry with proteins enabling biology and medicine" by Prof. Vishal Rai, Department of Chemistry, Indian Institute of Science Education and Research Bhopal.
18 Sep 2020
Department of Chemistry (online)
Talk Title : "Organic chemistry with proteins enabling biology and medicine"
About Speaker
Dr. Vishal Rai obtained his Ph.D. in Chemistry from IIT Bombay (Prof. I. N. N. Namboothiri, 2003-2008). He subsequently held a postdoctoral position and MITACS-Elevate fellow position at the University of Toronto, Canada (Prof. Andrei Yudin, 2008-2011). His contributions to peptide macrocycles created the platform for Encycle Therapeutics. Later, he joined the Department of Chemistry at IISER Bhopal in 2011. His research group is leading the development of chemical technologies for precision engineering of proteins. They are also involved in the synthesis of homogeneous antibody-drug conjugates, protein immobilization, and analytical tools for peptides and proteins. His research team wants to contribute towards the Society by enabling directed therapeutics and making precision therapeutics possible in the future. He is the Founder and Director of Plabeltech Private Limited. The company is empowered by state-of-the-art protein-engineering technologies such as LDMTM, Gly-TagTM, and MaspecterTM. He is the recipient of Swarnajayanti fellowship, Ramanujan fellowship, and DAE Young Scientist Award. Recently, he joined ACS Chemical Biology team as an Early Career Board member
Abstract
The chemical toolbox for investigating biological systems or enabling therapeutics requires the precise covalent attachment of tags to the proteins. In this perspective, we have been investing efforts to develop chemical technologies that can empower precise control over the site of bioconjugation. The critical barrier involves the simultaneous deconvolution of multiple challenges associated with reactivity and selectivity. In this perspective, we have developed a DisINtegrate or DIN theory that allows us to create new reactivity landscapes on the surface of a protein. Overall, it enabled the development of methods for (a) utilization of N-terminus as a reactivity hotspot,1 (b) single-site tagging of Lys or His,2 (c) N-Gly residue-specific labelling (Gly-TagTM),3 and (d) modular linchpin directed modification (LDMTM) for labelling single His or Lys residue.4 The LDM platform delivers single-site installation of various probes in native proteins. The user-friendly protocols result in analytically pure labelled proteins. The structure, enzymatic activity, binding to receptors, and downstream signalling pathways are typically unaffected. Importantly, these technologies allow access to homogeneous antibody-drug conjugates (ADCs) for directed cancer chemotherapeutics.4,5 The talk would highlight our journey and specific milestones that led to the development of a comprehensive platform for the precision engineering of proteins. Also, I will discuss the technological demands that we would like to address in the coming years
