In India, many biotechnological processes developed in various laboratories often remain on the laboratory shelves without entering the market place due to the lack of limited scale-up capabilities and resource constraint for technology commercialisation. In this regard, the pre-biotechnology process generator (PBPG) established in the Indian Institute of Chemical Technology (IICT) campus is a state of the art facility catered to facilitate scale-up of bench-scale laboratory processes (developed either at IICT or elsewhere) before the entrepreneurs take them further to the biotechnology incubators for large scale-up processes. This will enhance and accelerate their commercial credibility and generate pre-feasibility information needed for obtaining venture capital funding of biotechnology incubator centre (BTIC) projects. The overall mission of the PBPG is to develop bioprocesses and products by serving as a centre for entrepreneurship through development of collaborations with researchers from different universities, national R&D institutions and industry.
This facility will be made available to prospective clients of BTIC / outside parties for carrying out bench scale biotechnological / biotransformation processes on laboratory scale. It would also enable quick scale-up of the technology by researchers who have limited scale-up facilities of their own. The PBPG facility at IICT is available for industry and entrepreneurs for development of biotechnology-based processes / products on mutually agreed terms.
At present, this PBPG facility is equipped with different equipment like fermentors (of 7 and 20 L capacity), high speed refrigerated centrifuges, UV-Vis spectrophotometer, multimode spectrofluorimeter, phase-contrast and fluorescence microscope, PCR, FPLC protein purification system, gas and liquid chromatographic systems, lyophilizers, rotavaporators, CO2 incubator, deep freezers (with -30°C, -80°C and liquid nitrogen storage facility), walk-in cold cabinet, laminar flow hoods and biosafety level 3 cabinet for performing animal cell culture studies.
The different biotech-based processes / products that can be developed at PBPG include enzymes, organic/chiral intermediates, antibiotics, probiotics and recombinant DNA technology based-products. Some of the on going projects at the PBPG include the screening of different microbial strains isolated from different habitats for enzymes and other secondary metabolites of commercial or industrial importance catered to meet specific biotransformation reactions.
Chemical biology
Chemical biology is an interfacial area between chemical and biological sciences and primarily aimed at probing the complexity of biological processes by employing simple and small molecules generated through synthetic organic chemistry. These small molecules enable us in elucidating the mechanism of biological processes in detail with minimal perturbation. This interdisciplinary approach will expedite understanding of overall "molecular basis of life" by directly probing biological systems at chemical level. The primary objective of this institute in this area of science is to design/discover new and novel chemical entities through biological screening and vice versa and their application in developing novel therapeutic strategies for complex biological disorders, including their targeted delivery.
Although considerable effort has been invested in the discovery of selective anticancer drugs, most pharmacological approaches for the treatment of solid tumours suffer from poor selectivity. Therefore, the development of more selective therapeutic agents has become a major goal of current anticancer research. Within this framework, the use of non-toxic prodrugs designed to deliver the corresponding anticancer agent by specific enzymatic activation in cancerous tissues is being investigated. In this approach, the active enzyme may be naturally present in high concentration in the vicinity of the tumour (PMT strategy) or previously targeted to the tumour site using various strategies such as ADEPT, GDEPT, and PMT.
Pyrrolo[2,1-c][1,4]benzodiazepine (PBD) molecules like DC-81, its dimer DSB-120 and SJG-136 are potential chemotherapeutic agents with significant efficacy against some fast growing solid tumours. However, they exhibit some limitations, such as lack of selectivity and poor solubility. In order to improve selectivity of this class of molecules, the main pharmacophore, i.e., the imine functionality in these molecules is masked by a moiety that could enhance the selectivity by ADEPT, GDEPT and PMT strategies, while improving their solubility.
A series of PBD prodrugs will be designed, synthesised and evaluated for the selective toxicity against various cancer cell lines. Further these PBD prodrug molecules are expected to possess enhanced water solubility facilitating bioavailability and stability in comparison to the parent imine containing PBDs. Thus these studies could lead to a new class of chemotherapeutic agents with increased selectivity in the treatment of cancer.
(The authors are with Indian Institute of Chemical Technology)