Docking-based virtual screening of known drugs against murE of Mycobacterium tuberculosis towards repurposing for TB.

Repurposing has gained momentum globally and become an alternative avenue for drug discovery because of its better success rate, and reduced cost, time and issues related to safety than the conventional drug discovery process. Several drugs have already been successfully repurposed for other clinical conditions including drug resistant tuberculosis (DR-TB). Though TB can be cured completely with the use of currently available anti-tubercular drugs, emergence of drug resistant strains of Mycobacterium tuberculosis and the huge death toll globally, together necessitate urgently newer and effective drugs for TB. Therefore, we performed virtual screening of 1554 FDA approved drugs against murE, which is essential for peptidoglycan biosynthesis of M. tuberculosis. We used Glide and AutoDock Vina for virtual screening and applied rigid docking algorithm followed by induced fit docking algorithm in order to enhance the quality of the docking prediction and to prioritize drugs for repurposing. We found 17 drugs binding strongly with murE and three of them, namely, lymecycline, acarbose and desmopressin were consistently present within top 10 ranks by both Glide and AutoDock Vina in the induced fit docking algorithm, which strongly indicates that these three drugs are potential candidates for further studies towards repurposing for TB

Damping Study on MWCNT-Reinforced Al Composites

In this chapter, damping study on Aluminium-MWCNT based nanocomposites materials are discussed to increase the damping property for applications like engine head, pistons and cylinder blocks and other aerospace components. The Al-MWCNT composites were developed using Ball-milling, cold-isostatic, extrusion and compo-casting process. Corresponding, surface morphology and micro-structure study were discussed. The improved damping property of Al-MWCNT materials were discussed. The hysteresis damping of the composite material was understood by Tan delta and storage modulus (or) dynamic young’s modulus. Tan delta and storage modulus of Al-MWCNT composites were performed using dynamic mechanical analyser, by varying the temperature range from room temperature to 500°C (heating phases and cooling phases), at different frequencies. The Al-MWCNT shows some good damping property with increased temperature and decrease in storage modulus. The mechanisms behind the damping property were discussed

BIOACTIVE AND FUNCTIONAL PROPERTIES OF FISH PROTEIN HYDROLYSATE FROM LEIOGNATHUS BINDUS

Objective: The present work is focused on the production of biologically active protein hydrolysate from low value by-catch fish, Leiognathus bindus;this will be an ideal approach to exploit the underutilized fish to develop a highly nutritious bioactive product. Moreover, fish protein hydrolysateshave a broad spectrum of applications ranging from high-value peptones to food ingredients with special functional properties.Methods: The protein hydrolysate was prepared from L. bindus through acidic autolysis processes. The proximate composition, physico-functional,and biochemical properties of hydrolysate and control samples were characterized by standard protocols. Molecular profiling was done by sodiumdodecyl sulfate polyacrylamide gel electrophoresis and high-performance liquid chromatography analysis performed to identify the essential aminoacid composition in protein hydrolysate.Results: The results of this study reveals that the protein hydrolysate obtained from the trash fish has relatively high protein (71.01±0.2%) and lowlipid (1.57±0.1%) content. The molecular analysis shows low molecular weight peptides are obtained in the hydrolyzed samples which indicate highprotein solubility confirmed to have the potential application as an ingredient in the balanced human diet. The chemical score of the hydrolysateindicates that it fulfills adult human nutritional requirements.Conclusion: This approach also offers the relatively simple and cost-effective process to improve the nutritional characteristics and functional properties of foodstuff, also an opportunity for the conversion of waste fish resources to nutritious products, that can be used in food and pharmaceutical industries.Keywords: Protein hydrolysate, Emulsifying property, Bioactive, Peptides, Amino acid, Chemical score

Anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize.

Tumour resistance to radiotherapy remains a barrier to improving cancer patient outcomes. To overcome radioresistance, certain drugs have been found to sensitize cells to ionizing radiation (IR). In theory, more potent radiosensitizing drugs should increase tumour kill and improve patient outcomes. In practice, clinical utility of potent radiosensitizing drugs is curtailed by off-target side effects. Here we report potent anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize to tumours based on surface receptor expression. While two classes of potent anti-tubulins, auristatins and maytansinoids, indiscriminately radiosensitize tumour cells, conjugating these potent anti-tubulins to anti-ErbB antibodies restrict their radiosensitizing capacity. Of translational significance, we report that a clinically used maytansinoid ADC, ado-trastuzumab emtansine (T-DM1), with IR prolongs tumour control in target expressing HER2+ tumours but not target negative tumours. In contrast to ErbB signal inhibition, our findings establish an alternative therapeutic paradigm for ErbB-based radiosensitization using antibodies to restrict radiosensitizer delivery

Effects of multiple occupancy and inter-particle interactions on selective transport through narrow channels: theory versus experiment

Many biological and artificial transport channels function without direct input of metabolic energy during a transport event and without structural rearrangements involving transitions from a 'closed' to an 'open' state. Nevertheless, such channels are able to maintain efficient and selective transport. It has been proposed that attractive interactions between the transported molecules and the channel can increase the transport efficiency and that the selectivity of such channels can be based on the strength of the interaction of the specifically transported molecules with the channel. Herein, we study the transport through narrow channels in a framework of a general kinetic theory, which naturally incorporates multi-particle occupancy of the channel and non-single-file transport. We study how the transport efficiency and the probability of translocation through the channel are affected by inter-particle interactions in the confined space inside the channel, and establish conditions for selective transport. We compare the predictions of the model with the available experimental data - and find good semi-quantitative agreement. Finally, we discuss applications of the theory to the design of artificial nano-molecular sieves.Comment: 27 pages, 6 figures, 1 Appendix, in press in Biophysical Journa

Enhancement of Transport Selectivity through Nano-Channels by Non-Specific Competition

The functioning of living cells requires efficient and selective transport of materials into and out of the cell, and between different cellular compartments. Much of this transport occurs through nano-scale channels that do not require large scale molecular re-arrangements (such as transition from a ‘closed’ to an ‘open’ state) and do not require a direct input of metabolic energy during transport. Nevertheless, these ‘always open’ channels are highly selective and pass only their cognate molecules, while efficiently excluding all others; indeed, these channels can efficiently transport specific molecules even in the presence of a vast excess of non-specific molecules. Such biological transporters have inspired the creation of artificial nano-channels. These channels can be used as nano-molecular sorters, and can also serve as testbeds for examining modes of biological transport. In this paper, we propose a simple kinetic mechanism that explains how the selectivity of such ‘always open’ channels can be based on the exclusion of non-specific molecules by specific ones, due to the competition for limited space inside the channel. The predictions of the theory account for the behavior of the nuclear pore complex and of artificial nanopores that mimic its function. This theory provides the basis for future work aimed at understanding the selectivity of various biological transport phenomena

Cross-Reactive Sensor Arrays for the Detection of Peptides in Aqueous Solution by Fluorescence Spectroscopy

A simple but powerful method for the sensing of peptides in aqueous solution has been developed. The transition-metal complexes [PdCl2(en)], [{RhCl2Cp*}2], and [{RuCl2(p-cymene)} 2] were combined with six different fluorescent dyes to build a cross-reactive sensor array. The fluorescence response of the individual sensor units was based on competitive complexation reactions between the peptide analytes and the fluorescent dyes. The collective response of the sensor array in a time-resolved fashion was used as an input for multivariate analyses. A sensor array comprised of only six metal-dye combinations was able to differentiate ten different dipeptides in buffered aqueous solution at a concentration of 50 uM. Furthermore, the cross-reactive sensor could be used to obtain information about the identity and the quantity of the pharmacologically interesting dipeptides carnosine and homocarnosine in a complex biological matrix, such as deproteinized human blood serum. The sensor array was also able to sense longer peptides, which was demonstrated by differentiating mixtures of the nonapeptide bradykinin and the decapeptide kallidin