IISER Bhopal Scientists Invent Technology for Precision Engineering of Proteins – India Education | Latest Education News | Global Educational News
BHOPAL: Indian Institute of Science Education and Research (IISER) Bhopal researchers invented a new technology that can deliver active molecules to specific sections of proteins.
Scientists at IISER Bhopal have carried out studies on the “engineering” of protein molecules in recent years. Their serial technological breakthrough has gained in-depth insight into the chemical properties of these molecular machines. With this understanding, they developed the first modular platform for the precision mechanics of proteins.
The chemical modification of proteins is essential for the understanding of protein functions and the development of therapeutics and diagnostics.
The research team of the Departments of Chemistry and Biological Sciences at IISER Bhopal includes, among others, Dr. Vishal Rai, Dr. Ram Kumar Mishra, Dr. Sanjeev Shukla, Dr. Srinivasa Rao Adusumalli, Dr. Dattatraya Gautam Rawale and Dr. Neetu Kalra others who worked on this novel research.
The development of their Linchpin Directed Modification (LDM) platform was described in three articles published in the Journal of the American Chemical Society (2018), Angewandte Chemie International Edition - 2020, and Chemical Science (2021).
Protein modifications typically involve the attachment of specific chemicals to strategic sections of the proteins. Such protein modifications are common in nature, but the intricate machinery is difficult to replicate in the laboratory. The difficulty of attaching specific tags, markers and therapeutic molecules to specific protein regions arises from the complexity of the protein structure and the unspecific nature of many modifiers.
Dr. Vishal Rai, Associate Professor and Swarnajayanti Fellow, Department of Chemistry, IISER Bhopal, explained the importance of this research: Proteins in chemical reactions. "
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 supported by reagents made up of three key components. A representative example is FK, which quickly and reversibly binds to an amino acid called lysine, and FH, which reacts slowly but specifically to another amino acid called histidine.
Thus, FK first binds to the lysine in the protein and delivers FH to a proximal histidine of the protein. In addition, the spacer controls the exact location of the point. FK then separates and allows FH to be incorporated into the protein, thereby modifying it.
"A major advantage of our LDM platform is that it does not change the structure or the functions of the native protein," explains Dr. Rai. For example, the enzymatic activity of myoglobin, cytochrome C, aldolase and lysozyme C is retained even after labeling with the LDM reagent. Insulin, another protein, has also been shown to be absorbed by cells even after labeling with the LDM reagent.
The LDM reagents can precisely mark biologically active molecules such as antibodies that can be delivered precisely to the intended cells. The research team has shown that the LDM molecule successfully delivers a homogeneous conjugate of a monoclonal antibody and a drug to selectively inhibit breast cancer cells.
"The LDM platform offers unparalleled control over precision in protein engineering and a very powerful chemical toolkit for biology and medicine," said the lead researcher. One of the main applications pursued in the IISER laboratory is the development of antibody-fluorophore conjugates and antibody-drug conjugates. The platform will help cancer patients in the coming years with precise tumor imaging operations and targeted cancer chemotherapeutic agents. In other words, the technology would allow us to get rid of the tumors without harming the patient's healthy cells.
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