RESEARCH COLLABORATION

ACADEMIC COLLABORATION IN ABROAD

(I)   In USA: Prof. Jiantau Guo, Department of Chemistry, University of Nebraska-Lincoln, USA

My conceptual unnatural amino acid library and the scaffold amino acids/peptidomimetics have attracted the interest of Prof. Jiantau Guo of Nebraska-Lincoln, USA. Therefore, collaboration is build up with for site-specific incorporation of fluorescent triazolyl unnatural amino acids into protein and study of protein function and dynamics. Moreover, incorporation of functionalized amino acids, such as the developed ^NCSLys/ ^NCSAla [Ref. 13, 25] into protein systems, could enable site-specific labeling /ligation at the physiological condition. Further, my unnatural nucleobases could serve as a part of four base codons in mRNA, which can be exploited to code for triazolyl unnatural amino acids/ ^NCSLys using an engineered orthogonal aminoacyl-tRNA synthetase (AARS) and tRNA pair. Such study would ultimately allow them for translating the genetic alphabet into a genetic code.

(II)   In Japan: Prof. Isao Saito, Institute of Advanced Energy, Kyoto University, Japan

SARS-CoV-2 (2019-nCoV) coronavirus is posing dangers worldwide at the very moment. Currently, the clinical treatment of the disease, COVID-19, is mainly symptomatic combined with the repurposing of already marketed antiviral drugs such as ritonavir/lopinavir, remdesivir, a combination of ritonavir/lopinavir with interferon beta, and antibiotics such as Chloroquine and hydroxychloroquine to treat secondary infections. Therefore, there remains an urgent need and challenge to save human life worldwide by developing specific antiviral therapeutics and vaccines against SARS-CoV-2.  RNA-dependent RNA polymerase (RdRp) plays crucial role to make multiple copies of viral genomic RNA. Thus, design of inhibitor drugs for RdRp is an excellent strategy to stop viral replication and hence spread of viral diseases. Recently, it has been found that some of the drugs, such as, ribavirin and remdesivir, developed for SARS, MERS etc. are also effective for SARS-CoV-2. The approved influenza drug, Favipiravir (Avigan) selectively inhibits the RNA polymerase of the influenza virus, an enzyme required for viral replication once human host cells are infected. COVID-19 also uses this enzyme to replicate and is classified into the same type of single-stranded RNA virus like influenza. Recently, Avigan is used as the only drug to help tackle the spread of the COVID-19 pandemic in Japan. Phase III clinical trials are ongoing in Japan. In the US, Fujifilm started Phase II trials earlier in April 2020. The structures of Avigan and other antiviral drugs which are being used for COVID-19 treatment and the target analogs are given below. In this Global crisis and as a continuation of the research efforts for the synthesis of novel nucleosides, I recently involved in collaborative work with Prof. Isao Saito, Kyoto University, Japan, for developing antiviral nucleosides such as Avigan and AICAR analogs. Considering the effectiveness of Avigan against Coronavirus and the side effects of other nucleoside based drugs, they came up with few target designed analogs. Our preliminary Molecular Docking study suggested them replacing the ribose moiety by linear alcohol as is there in acyclovir. Furthermore, the triazole containing bases shows strong interaction and binding effect reflecting their activity to stop the extension of RNA of the viruses. The target nucleosides are believed to have mechanism of action which is similar to Avigan. This collaborative work would yield a highly effective COVID-19 drug.

(III)   In UK: Prof. K. H. Aaron Lau, Pure and Applied Chemistry, The University of Strathclyde Glasgow, UK

In a meeting in India, Prof. K. H. Aaron Lau, University of Strathclyde, Glasgow, UK, has got attracted by the exciting peptidomimetic candidates developed by me. Thus, we are now engaged in a collaboration in developing bioinspired materials and peptide/peptoids based biomaterial for pssible clinical use. We are engaged in creating new and novel therapeutic alternatives against the recent rise of multidrug-resistant microbial strains. We are now in a process to put up a project proposal based on the recent call for Team Science Grant & Clinical/Public Health Research Centres Grants from IndiaAlliance DBT. We want to exploit the β-turn/β-sheet Peptidomimetics developed by Dr. Bag, Peptoids by Prof. Aaron and the Surface tethering techniques by Prof. Lalit at BSBE Department of IITG to create therapeutic surfaces. The bioinspired materials based on fluorescent peptidomimetics developed by me could also find applications in sensing and medical diagnostic purposes. This project would have great impact to resist virus protein capsids, such as SARS-CoV-2 and similar SARS viruses, from surface attachment.

COLLABORATION WITH INDUSTRIES

(I)      Merck Life Science Pvt. Ltd., Germany

I have recently developed universal linker containing nucleoside, 5-(3-((4-ethynylphenyl)(methyl)amino)propynyl)-2'-deoxyuridine, (^EPMAPU Linker) [Ref. 16]. This nucleoside is highly useful for post-synthetic modification of DNA followed by generation of fluorescent ODN probes via Click Chemistry, Sonogashira Coupling or Glaser Coupling protocols. Such fluorescent ODN probes exhibiting polarity sensitive Intramolecular Charge Transfer (ICT) emission are his unique contribution. Thus, these post-synthetically generated fluorescent ODN probes can be utilized in genetic analysis, SNPs detection, Highthroughput screening and other biotechnological/chemical genomics applications. Soon after the development, the Regional Manager of Merk Life Science Pvt. Ltd., Germany, has invited Dr. Bag for sharing the molecule and the process. Now, this nucleoside is considered for commercialization soon.

(II)   M/s Rasayan Inc., USA

The report of oxo-pyrene-dU-labelled fluorescent oligonucleotide (ODN) as an efficient probe for SNPs genotyping [Ref. 55] has iattracted the attention of the President of Rasayan Inc., USA. He soon became interested in collaborative work and for large scale production of the probe DNA for further chemical genomics applications. This is also considered as “antisense oligonucleotide,” and the therapeutic application in nurological disorder will also be studied. our developed nucleosides-(a) ^TPhenB_Do/^TNBB_Ac [Ref. 42], (b) doubly widened Fused Triazolyl Phenanthrene (FTPhen) [Ref. 22] and (c) angularly widened Fused Triazolyl-2-Quinolinone (FTQuon) [Ref. 14] are found to be useful for the design of DNA-based light harvesting material and generating probe for DNA detection. Hence, these nucleosides are under consideration for large scale production.

(III)     Sapala Organics Pvt. Ltd., Hyderabad, India

The aforementioned unnatural nucleosides showed potential biological activity against bacterial strain. Thus, Dr. Shyam Banerjee, the Head of R & D of Sapala Organics Pvt. Ltd, shows interest for large scale production of these nucleosides and further studying their antiviral activity in details.

(I)      Prof. Amit Basak, Chemistry and Scholl of Bioscience, IIT Kharagpur, India

My collaborative work with Professor Amit Basak, IIT Kharagpur, for selective leballing and visualization of carbonic anhydrase (HCAII) and penicillin binding proteins (PBPs) utilizing azido naphthalimide-sulphonamide/ampicilin template is a noteworthy contribution in the field of proteomics for understanding cellular processes and also in drug design. This study makes the template universally appealing and shed light for the development of selective probes for capturing β-lactamase [Ref. 27 (Cover Page, Chem. Commun. 2017)].

(II)   Prof. Dipak K. Goswami, Department of Physics, IIT Kharagpur, India

Application- OFETs Sensor for Biomedical/Defense Application: The axially chiral amino acid scaffolds ^ArTAA has been elegantly exploited for discrimination of methanol from ethanol both in liquid and gaseous state via a switch on fluorescence response [Ref. 24]. This is a simple technique that would be attractive to develop a system that could estimate ethanol content on-the-spot. This work has recently been acknowledged as “worthy of commendation” by Dr. Wael A., Chief Author, London Journals Press. He also mentioned, “I found your research work to be distinctive and can indeed be significant for fellow researchers and scientists working in the same domain”. Thus, the Editorial Board has recognised Dr. Bag under "Quarterly Franklin Membership" (Membership ID#BP95271). Inspired by this innovative work, Prof. Dipak K. Goswami, Department of Physics of IIT Kharagpur, has invited him for a collaboration. Thus, these chiral amino acids and fluorescent peptides are in use to develop practical sensory devices based on organic Filed Effect Transistors (OFETs). They have developed a semiconducting bilayer geometry in OFET design. It includes one highly conducting pentacene layer coated with a fluorescent peptide layer (fluorescent ^ArTAA_Py-Py pentapeptide).  Such a device has been tested for the detection of polar gas molecules like alcohol and acetone at room temperature. It also can detect blood proteins in solutions successfully. This is the first example of a peptide based OFET device which is thus unique in design. It is also advantageous in comparison to other available gas sensing devices as it works efficiently at room temperature, exhibits higher selectivity and enhanced sensitivity. The part of the work entitled, “Fabrication of Peptide-based room temperature gas sensors using organic field-effect transistors,” was presented in a conference, “The Swiss Conference on Printed Electronics and Functional Materials (Swiss ePrint 2019), 5^th Edition” in Switzerland. The paper has well been appreciated and recognized to offer a Best Poster Award. [Ref. 24, 84]. Additionally, we are also working to integrate microfluidic channels to convert OFETs for the rapid detection of biomolecules in the solution phase and also would be extended for the detection of chemical/biological warfare agents. Both the findings are under preparation for filing a patent. The initial conceptual development involved in this work is a part of a CSIR project.  In a progress review meeting, one of the expert members who is also a leading scientist in India has very nicely appreciated the work [Ref. 24, 84].