OBCL: Organic and bioconjugate chemistry LABoratory

        PES          Ab         LysC_assembly

research 

Chemical methods for "precision engineering of proteins"

Why is it important?

Chemical biology research often requires precise covalent attachment of tags to the proteins. Such methods enable bioimaging, biophysical investigations, disease diagnosis, and protein-based therapeutics.

Making it possible!

Chemical methods for precise single-site modification of native proteins was not considered a realistic approach. We try to understand the reasons that strengthened this school of thought. In this perspective, we deconvolute the challenges and probe them one by one. We invest efforts to address a few primary questions:

(a) How does the protein behave as a substrate in a chemical transformation? (b) Can a multi-step chemical process deconvolute multiple challenges of selectivity? (c) Can we develop chemical methods for single-site modification of native proteins? (d) Is it possible to have a modular chemical method for precision protein engineering?

The first step toward these targets involves understanding the reactivity landscape of proteins. The critical challenge relates to the identification of physical organic chemistry principles that would allow us to generate reactivity biases at specific sites of the protein.

Technologies:

(a) LDM technology: Modular linchpin directed modification for labelling His (stay tuned for more).

(b) Gly-tag technology: N-Gly residue specific labelling.

(c) Reactivity hotspot technology: N-terminus, Lys, and His (stay tuned for more).

Contributions: 

(a) Principles and a chemical toolbox for precision engineering of proteins. (b) Methods to regulate chemoselectivity and site-selectivity. (c) Single-site protein modification with potential to regulate the site and residue. (d) Precise installation of diverse biophysical and biochemical probes. Example - fluorophore, affinity probe, NMR tag, etc. (e) User-friendly protocols to isolate analytically pure labelled proteins without adversely affecting their structure and activity. (f) Ordered single-site immobilization of proteins and enzymes. (g) Tagged insulin with conserved activity, binding to receptors, and downstream signalling pathways. (h) Homogeneous antibody-drug conjugates for directed cancer chemotherapeutics.

 

Funding agencies: SERB, DST, DAE, DBT, BIRAC, IISER Bhopal 

Links

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IISERB

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For details about research@VR group, contact vrai@iiserb.ac.in