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An Overview of Protease Inhibitors
Published in Se-Kwon Kim, Marine Biochemistry, 2023
Veena Sreedharan, K.V. Bhaskara Rao
The first phase in the drug development process is to find and choose a pharmacological aim that is important in a specific biological pathway. To find a drug goal in a pathogen, there must be no doubt that the assumed target is either expressly preoccupied in the host or significantly vary from the host counterpart in order for it to be used as a medicine target. Ultimately, protein is critical for the microbe’s existence or for directing a target toward certain pathway. Due to their involvement in the regulation of certain biochemical and metabolic pathways, enzymes are the most significant targets. For specific suppression of the aimed sites, the target enzymes should have considerable structural and functional variations from mammalian systems. As a result, specialized inhibitors that bind to the most potential sites of enzymes and led to the inhibition of enzymes and the viability of cell can be created or found in nature. Finally, it is critical that the chosen target be assayable, allowing compounds to be screened using a cost-effective particular assay technique (Shukla et al., 2010). Additionally, targeting multiple enzymes in a metabolic pathway is more beneficial and successful. Even if certain parasites are eukaryotes, their cell architecture differs significantly from that of mammalian cells, making it possible to identify parasite- specific targets.
Finding a Target
Published in Nathan Keighley, Miraculous Medicines and the Chemistry of Drug Design, 2020
The instructions for producing proteins are encoded on genes, sections of DNA, which are transcribed on to RNA before being translated into a protein chain at ribosomes; cell organelles designed for this operation. This is a very intricate enzyme-controlled biological pathway, with a high degree of complexity. Proteins produced from this process then adopt their specific three-dimensional shape and move to their intended location to perform a given function in the body. Nucleotide triplets code for particular amino acids; the order in which these triplets are assembled in the gene determines the sequence of amino acids in the protein and therefore ultimately governs the proteins shape and function. The different side chains of each of the 20 amino acids can form a variety of hydrogen bonds; hence the observed variety of possible structures. Proteins are very versatile molecules that can have many functions, governed by their structural organisation. For globular proteins such as those involved in catalysis and molecular recognition, the final folded three-dimensional shape of a polypeptide, the tertiary structure, may constitute one protein domain, and several globular units comprise the functional quaternary structure, as with haemoglobin. In order for polypeptides to assemble into a functioning quaternary structure, precise interactions between these molecules must be in place.
Microalgae for Sustainable Fuel Technology
Published in Gokare A. Ravishankar, Ranga Rao Ambati, Handbook of Algal Technologies and Phytochemicals, 2019
Surajbhan Sevda, Dipak A. Jadhav, S.P. Jeevan Kumar, T.R. Sreekrishnan
Microbial fuel cells are aimed to generate energy by converting the chemical energy to electrical energy through biological pathway. The biological substrates include sewage sludge, municipal wastewater and agricultural wastes. Several studies have been conducted on the coupling of microalgae and MFC (Raschitor et al., 2015; Yu et al., 2015), that lead to microalgae-MFC (mMFC) development (Cao et al., 2009; Wieczorek et al., 2015). In mMFC, photosynthetic microorganisms readily convert the solar energy into electrical energy (electricity) via metabolic reactions (Bombelli et al., 2011). Moreover, application of mMFCs not only generate bioelectricity but also sequestrate CO2 from air and get rid of nitrogen from air and contaminants from waters (Figure 9.2) (Li et al., 2012; Wang et al., 2010).
Adverse outcome pathways and linkages to transcriptomic effects relevant to ionizing radiation injury
Published in International Journal of Radiation Biology, 2022
Jihang Yu, Wangshu Tu, Andrea Payne, Chris Rudyk, Sarita Cuadros Sanchez, Saadia Khilji, Premkumari Kumarathasan, Sanjeena Subedi, Brittany Haley, Alicia Wong, Catalina Anghel, Yi Wang, Vinita Chauhan
A stable identifier is assigned to each mapped biological pathway in the Reactome analysis result, from which a hierarchy of locations in the Pathway Browser could be found. The top of the locations is identified as the high-level biological processes, including seven locations covering the 92 biological pathways. Therefore, the seven high-level biological processes of the significant biological pathways with corresponding genes were classified as potential AEs to the proposed lung cancer AOP 272 (Figure 2). The AEs were categorized as follows: twenty-three biological pathways are involved in cell cycle processes, such as mitotic G1 phase, G1/S transition, G2/M transition, etc. Seventeen biological pathways are involved in immune system regulation, including antigen presentation, endosomal/vacuolar pathway, ER-phagosome pathway, etc. Five pathways were associated with DNA replication and DNA repair, respectively. Additionally, oxidative stress-induced senescence was identified in the high-level biological process of cellular responses to stimuli.
Proteomics in the pharmaceutical and biotechnology industry: a look to the next decade
Published in Expert Review of Proteomics, 2021
Jennie R. Lill, William R. Mathews, Christopher M. Rose, Markus Schirle
In the past decade we have seen advances in various omics techniques including genomics, transcriptomics, proteomics, and metabolomics. An emerging systems biology approach attempts to gain a holistic sense of an organism, cell or biological pathway by analyzing these data sets together to form a comprehensive molecular understanding of a given biological pathway. This is no easy task, as each of these data sets is produced under various biophysical conditions, with nuances to data analysis let alone data integration. Many of these biomolecules are linked in disparate ways, not directly relating to our organized view that is the central dogma for these fields. Metabolites and short chain fatty acids for example, represent the downstream products of multiple interactions between various genes, transcripts, and proteins. Identifying metabolites alone does not give one the whole story about how a cell is signaling, what it is interacting with or under what cellular state it is in, but it can offer important clues. For some analyses that are routinely performed there is still some ‘guess work’ involved, or at least incorporation of algorithms that make assumptions about the data that is being used as a database or to interpret downstream analyses. One example of this is the recent exploration of ‘dark matter’ material in our genome, or the genome/proteome of an individual that does not confer to the traditional paradigm of proteins being produced due to canonical translation events.
Application of adverse outcome pathway networks to integrate mechanistic data informing the choice of a point of departure for hydrogen sulfide exposure limits
Published in Critical Reviews in Toxicology, 2021
Katy O. Goyak, R. Jeffrey Lewis
A biological pathway-based approach is a means to incorporate different lines of evidence into a single framework to increase confidence in the identification of a biologically plausible effect that can be used to derive a health-protective exposure limit. In this analysis, animal and human data from 34 studies identified from existing systematic literature reviews on H2S were used to propose an Adverse Outcome Pathway (AOP) network, composed of 4 AOPs sharing 1 molecular initiating event (MIE) and 4 potential outcomes. Potential health-protective critical effects (cytochrome oxidase inhibition, neuronal cell loss, olfactory nasal tumors) were identified through consideration of effect levels to distinguish lower- from higher-dose outcomes, followed by a more focused assessment of dose-temporal concordance specific to the H2S-data.