Zero Hunger (SDG 2), Good Health & Well-being (SDG 3)
Chemical technologies for precision engineering of proteins and antibodies
Vishal Rai * Department of Chemistry, Indian Institute of Science Education and Research Bhopal
The chemical toolbox for investigating biological systems or enabling biologics requires the precise covalent attachment of tags to the proteins. In this perspective, we have been leading the efforts toward chemical technologies to enable 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, our DisINtegrate or DIN theory creates new reactivity landscapes on a protein's surface. 1 As a result, it enabled the development of methods for targeting reactivity hotspots, 2 N-Gly residue-specific labelling (Gly-Tag®), 3 and modular Linchpin-Directed Modification (LDM®).4 This comprehensive technological platform offers homogeneous antibody-drug conjugates (ADCs) for directed cancer chemotherapeutics and fluorophore conjugates (AFCs) for imaging-guided tumour surgery. 4,5 Besides, our findings create an opportunity to realize precision therapeutics with small molecules. The presentation would highlight the approach and principles that inspired the precision engineering of proteins and antibodies.
Figure. Human behavior-inspired Disintegrate (DIN) theory enables the precision engineering of proteins and antibodies. References 1. DIN Theory: ACS Cent. Sci. 2023, doi: 10.1021/acscentsci.2c01455. 2. Reactivity hotspots: (a) Chem. Commun. 2021, 57, 7083. (b) Chem. Commun. 2019, 55, 1100. 3. Gly-Tag® technology: (a) Chem. Sci. 2020, 11, 13137. (b) Nat. Commun. 2019, 10, 2539. 4. LDM® platform, AFC/ADC: (a) Nat. Commun. 2022, 13, 6038. (b) Chem. Sci. 2021, 12, 6732. (c) Angew. Chem. Int. Ed. 2020, 59, 10332. (d) J. Am. Chem. Soc. 2018, 140, 15114. 5. Our other ADCs: (a) Nat. Biomed. Eng. 2019, 3, 917. (b) Chem. Commun. 2019, 55, 9979.
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© The Author(s), 2023
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