IISER Bhopal researchers have developed a technology named ‘BHoPAL’ for attaching chemical tags to proteins, an important process in the development of drugs.
Through this technology, necessary chemical moieties can be linked to specific sites of a protein without harming the protein’s efficacy.
Process
This process is essential for two main purposes:
1. Attaching proteins to fluorescent chemical tags for their visualization inside cells enabling studies focused on understanding how they perform cellular functions.
2. Linking drugs to antibody proteins for selective drug delivery to diseased cells such as cancerous cells preventing undesirable side-effects of these drugs.
Proteins
Proteins are extremely prone to loss of function when treated with chemical reagents. However, for the first time, IISER Bhopal’s novel technique eliminates this problem.
This technology is called ‘Baylis Hillman orchestrated Protein Aminothiol Labelling’ (BHoPAL) which efficiently tags chemicals to proteins without compromising their function, say sources from IISER Bhopal.
Team
The research was led by Dr. Dimpy Kalia, Assistant Professor, Department of Chemistry, IISER Bhopal who supervised her PhD students, Mudassar H Mir, Sangeeta Parmar, and Chhaya Singh on this project.
Their findings have been published in the reputed, peer-reviewed journal Nature Communications (https://doi.org/10.1038/s41467-024-45124-2).
Objectives
Dr. Dimpy Kalia, Assistant Professor, Department of Chemistry, IISER Bhopal elaborated on the objectives of this research.
She said proteins are cellular entities that play crucial roles in all cellular functions.
Protein dysfunction results in major life-threatening diseases such as Alzheimer’s disease, Parkinson’s disease, etc.
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Hence, developing effective approaches to study proteins in cells is crucial for developing therapeutic approaches targeting them, said Dr Kalia of IISER Bhopal.
Test
To test this platform, the researchers developed a new chemical reaction that has never been explored before.
This reaction occurs between N-Cysteine, an important amino acid present in proteins, and Baylis Hillman adducts, and results in the formation of a linkage (a bis-heterocyclic scaffold) on specific sites on the protein, say IISER Bhopal researchers.
Labelling multiple sites of a protein is extremely difficult, but by using this approach, researchers can easily accomplish this task within a few minutes, say IISER Bhopal researchers.
Diverse Applications
Elaborating further, Dr. Dimpy Kalia of IISER Bhopal said, “What we have developed has diverse applications in chemical biology, synthetic chemistry, and medicinal chemistry.
Protein conjugates fabricated using our BHoPAL technology shall be employed for the fabrication of antibody-drug conjugates (ADCs) for cancer therapy, said Dr Dimpy of IISER Bhopal.
Moreover, the BHoPAL technology shall also contribute tremendously to basic biological research by enabling the imaging of proteins within human cells, said Dr Dimpy.
Chemical Agents
What stands out is that this technology easily allows chemical agents to be attached to any site of the protein, a process that was very difficult to achieve before.
This is a promising development that shall find applications in disease diagnosis, cellular imaging, drug development, and understanding drug-target interactions on a molecular level.
About IISER Bhopal
Established by the Ministry of Education (then Ministry of Human Resource & Development), Government of India, in 2008.
IISER Bhopal is the youngest of the first five IISERs. In a decade, the Institute has received several distinctions, duly carving out its position in the national and international arena.
With a vision to provide high-quality education to students and contribute to society through its research, IISER Bhopal is the first IISER to have been declared by the Ministry of Education for project completion.
IISER Bhopal is continuously consolidating its position in the National and International rankings and has secured 60th place in The National Institutional Ranking Framework, Ministry of Education, Government of India.
Along with this, IISER Bhopal was placed at rank 4th in India (Academic sector) in the Nature Index Rank 2023 and rank 281-290 in the overall category of the QS Asia Ranking 2023.
The Institute has also been ranked 57th (National Rank, out of 70 in the 1500 Institutes) in the Times Higher Education 2023 World Ranking.