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Pushing the boundaries of functional protein nanotechnology

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Dr. Britto Sandanaraj’s group is working on developing new technologies and engineering new molecules for applications in the field of chemical biology and molecular imaging. In a recent set of papers, the group reported synthesis of new types of self-assembling artificial proteins and design of protein-based nanoreactors.

On artificial proteins and why create them

Proteins are like little machines in cells and carry out many tasks in living organisms. They build the body, fight infection, digest food, transport nutrients, and so on. In spite of the great diversity of proteins in nature, our curiosity to understand how they function, and if we can employ them to fix malfunctions, has led scientists to modify proteins and to explore making artificial designer versions of proteins.

The field of protein nanotechnology is relatively new compared to other nanotechnologies which are based on biological molecules such as DNA, RNA, peptide, carbohydrates and lipids. The last decade witnessed the invention of breakthrough technologies in the area of protein nanotechnology. Computational protein design matured as a robust method for the construction of custom-designed protein nanomaterials of defined size and shape. Although extremely powerful, it is restricted to the standard 20 amino acids that make up the natural proteins. In order to address the limitations of previous methods, Britto’s group is working on developing on chemical technologies for design of artificial proteins with new functions.

Dr. Sandanaraj’s group had earlier developed a new chemical biology method to label proteins through the use of micelles, for which a US patent has been granted and 3 other US patents have been filed and published (see a list below). The technology is also being explored for its applicability in collaboration with a pharma/biotech company each in the US and in India.

Termed ‘Micelle-Assisted Protein Labeling Technology’, and MAPLabTech for short, this chemical biology approach  expands the possibilities for the design of protein nanomaterials with advanced functions.

In this set of papers, the group further expands the scope of MAPLabTech.

Rapid chemical synthesis of self-assembling artificial proteins (SAPs)

Synthesis of well-defined monodisperse SAPs was earlier reported by Britto’s group. However, the reported method involved a very tedious synthesis of chemical probes and therefore posed a challenge to synthesise a diverse library of SAPs in a short time. To address that limitation,  the group introduced a click chemistry strategy for the rapid synthesis of SAPs. This method cut down the number of synthetic steps and therefore aid in synthesizing diverse SAPs in a very short time.

Pavankumar Janardhan Bhandari, Mullapudi Mohan Reddy, Kasuladevu Jegannadha Rao, and Britto S. Sandanaraj (2021). Rapid chemical synthesis of self-assembling semi-synthetic proteins. Journal of Organic Chemistry 86(13):8576-8589. 

Rational design of redox-sensitive self-assembling artificial proteins

Using MAPLabTech, Britto’s group designed redox-sensitive self-assembling artificial proteins. These proteins are capable of self-assembling into protein nanomaterials of defined size and shape containing engineered disulfide functionality. The treatment of protein nanomaterials with dithiothreitol (DTT) leads to disassembly of protein nanoparticles into individual proteins due to cleavage of disulfide bonds. As the assembly and disassembly can both be controlled, this work has potential applications in gene therapy, in vivo imaging and targeted drug delivery.

Pavankumar Janardhan Bhandari, Britto S. Sandanaraj (2021). Rational design of programmable monodisperse semi-synthetic protein nanomaterials containing engineered disulfide functionality. ChemBioChem


A universal chemical method for design of protein-based nanoreactors

The group combined N-terminal bioconjugation, a method used to modify proteins, with MAPLabTech to design protein-based nanoreactors, which are capable of catalyzing a particular chemical reaction. They have demonstrated this concept with a wide range of proteins. The group is working on utilising MAPLabTech for the design of SAPs by exploiting site-specific cysteine bioconjugation.

Mullapudi Mohan Reddy, Punita Bathla, Britto S. Sandanaraj (2021). A universal chemical method for rational design of protein-based nanoreactors. ChemBioChem


Patents from Dr. Britto's research group

1. Sandanaraj, B. S., Reddy, M. M., Bhandari. Generation-dependent supramolecular assemblies of protein-dendron conjugates. US Patent US 2021/0163916 A1 (Published June 2021)

2. Sandanaraj, B. S., Reddy, M. M. Chemical method for synthesis of protein amphiphiles. US Patent 2020/0199175 A1 (Published June 2020)

3. Sandanaraj, B. S.; Bhandari, P. J., Reddy, M. M. Supramolecular protein assemblies with advanced functions and synthesis thereof. US Patent, 2019/0134212 A1 (Published May 2019)

4. Sandanaraj, B. S., Reddy, M. M., Bhandari, P. J.; Rao, K. Hydrophobin mimics: Process for preparation thereof. US Patent 10,188,136 B2 (Granted – Jan 2019)