Bhopal: Researchers at the Indian Institute of Science Education and Research (IISER) Bhopal announced on Monday, the launch of their new technology invention for protein engineering, that they have named Linchpin Directed Modification (LDM) platform. Protein Engineering or chemical modification of proteins is significant for researchers to understand the protein functions that helps in the development of therapeutics and diagnostics.
The LDM Platform technology developed by IISER researchers works by delivering active molecules to specific sections of proteins.
One of the main applications being pursued in the IISER laboratory is the development of antibody-fluorophore conjugates and antibody-drug conjugates. The platform will help cancer patients with precise imaging-guided tumor surgeries and directed cancer chemotherapeutics in the coming years, the release stated.
Protein modifications typically involve attaching specific chemicals to strategic sections of the proteins. Such protein modifications are commonly seen in nature, but the intricate machinery is challenging to replicate in the lab. The difficulty in attaching specific tags, markers, and therapeutic molecules to specific protein regions arises from the complexity of the protein structure and the non-specific nature of many of the modifiers, it said.
The Research Team consisted of Dr. Vishal Rai, Dr. Ram Kumar Mishra, Dr. Sanjeev Shukla, Dr. Srinivasa Rao Adusumalli, Dr. Dattatraya Gautam Rawale, and Dr. Neetu Kalra, among others from the Departments of Chemistry and Biological Sciences at IISER Bhopal.
Their technological invention or Linchpin Directed Modification (LDM) platform has been described in three papers published in the Journal of the American Chemical Society (2018), Angewandte Chemie (International Edition – 2020), and Chemical Science (2021).
Explaining the research, the release said, “Proteins are built of amino acids; there are 21 amino acids that make all the proteins.”
“It (LDM Platform) is empowered by reagents made of three key components. A representative example involves FK that rapidly and reversibly attaches to an amino acid called lysine and FH that reacts slowly, but specifically to another amino acid – histidine. Thus, FK first attaches itself to the lysine in the protein and delivers FH to a proximal Histidine of the protein. Moreover, the spacer controls the exact location of the site. FK then detaches and allows FH to be installed into the protein, thus modifying it.”
Dr. Vishal Rai, Associate Professor and Swarnajayanti Fellow, Department of Chemistry, IISER Bhopal, said, “A key advantage of our LDM platform is that it does not modify the structure or functions of the native protein.”
For example, the enzymatic activity of myoglobin, cytochrome C, aldolase, and lysozyme C, are conserved even after labelling using the LDM reagent. Insulin, another protein, has also been shown to be absorbed by cells even after tagging with the LDM reagent, the release added.
“The LDM reagents can precisely label biologically active molecules such as antibodies that can be delivered accurately at the designated cells. The research team has shown that the LDM molecule successfully delivers homogeneous conjugate of a monoclonal antibody and drug for selective inhibition of breast cancer cells,” it further added.
“The LDM platform provides unprecedented control over precision in protein engineering and a very powerful chemical toolbox for biology and medicine,” added the lead researcher.
News source- Economic Times