IISER Bhopal scientists invent protein precision engineering

Indian Institute of Science Education (IISER) Bhopal researchers have invented a new technology that can deliver active molecules to specific sections of proteins.

IISER Bhopal scientists have been studying the “manipulation” of protein molecules over the last few years. Their continuous technical breakthroughs have provided detailed insights into the chemical characteristics of these molecular machines. Based on this understanding, they designed the first ever modular platform for protein precision engineering.

Chemical modification of proteins is essential for understanding the function of proteins and for developing therapeutic and diagnostic methods.

IISER Bopar’s Faculty of Chemistry and Biological Sciences research team includes Dr. Vishal Lai, Dr. Ram Kumar Mishra, Dr. Sanjeve Shukla, Dr. Srinivasa Lao Adusmari, Dr. Dattatraya Gotama Rawale, Dr. Nitu Kara It will be. Others working on this new research.

The development of their Linchpin Directed modified (LDM) platform is described in three papers published in the Journal of the American Chemical Society (2018), Angewandte Chemie (International Edition-2020), and Chemical Science (2021). ..

About research

Modification of a protein usually involves adding certain chemicals to the strategic section of the protein. Such protein modifications are common in nature, but complex mechanisms are difficult to reproduce in the laboratory. The difficulty in attaching specific tags, markers, and therapeutic molecules to specific protein regions stems from the complexity of protein structures and the many non-specific properties of modifiers.

Regarding the significance of this research, Dr. Vishal Rai, Associate Professor and Swarnajayanti Fellow of the Faculty of Chemistry, IISER Bhopal, said: Protein in a chemical reaction. “

Proteins are made up of amino acids. There are 21 amino acids that make up all proteins. The research team has developed a technology they call the “LDM platform.” It is fortified by reagents that consist of three major components. Typical examples include FK, which binds rapidly and reversibly to an amino acid called lysine, and FH, which reacts slowly but specifically to another amino acid, histidine.

Therefore, FK first binds to the protein lysine and delivers FH to the protein’s proximal histidine. In addition, spacers control the exact location of the site. The FK is then cleaved and the FH is incorporated into the protein, thereby modifying the protein.

“The main advantage of our LDM platform is that it does not change the structure or function of natural proteins,” explains Dr. Rai. For example, the enzymatic activities of myoglobin, cytochrome C, aldolase, and lysozyme C are preserved even after labeling with LDM reagents. Another protein, insulin, has also been shown to be absorbed by cells even after tagging with the LDM reagent.

LDM reagents can accurately label bioactive molecules such as antibodies that can be accurately delivered to designated cells. The researchers have shown that the LDM molecule successfully delivers a homogeneous conjugate of a monoclonal antibody and a drug for the selective inhibition of breast cancer cells.

“The LDM platform provides unprecedented control over the accuracy of protein engineering and a very powerful chemical toolbox for biology and medicine,” said the principal investigator. One of the major applications pursued at the IISER laboratory is the development of antibody-fluorofore conjugates and antibody-drug conjugates. The platform will assist cancer patients with accurate image-guided tumor surgery and directed cancer chemotherapy over the next few years. In other words, this technique will allow the tumor to be removed without damaging the patient’s healthy cells.