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Green-Synthesized Nanoparticles as Potential Sensors for Health Hazardous Compounds
Published in Richard L. K. Glover, Daniel Nyanganyura, Rofhiwa Bridget Mulaudzi, Maluta Steven Mufamadi, Green Synthesis in Nanomedicine and Human Health, 2021
Rachel Fanelwa Ajayi, Sphamandla Nqunqa, Yonela Mgwili, Siphokazi Tshoko, Nokwanda Ngema, Germana Lyimo, Tessia Rakgotho, Ndzumbululo Ndou, Razia Adam
At present, there are two main approaches for the fabrication of nanostructures and the synthesis of nanomaterials: “bottom-up” and “top-down” approaches (Fig. 13.4). The top-down approach is a physical method known as microfabrication method where suitable bulk materials break down into fine particles by size reduction with various lithographic techniques such as milling, thermal/laser ablation, grinding and sputtering (Singh et al., 2016). However, the operative and acceptable method for nanoparticle preparation is the bottom-up approach where nanoparticles are synthesized using either biological or chemical methods through the self-assembling of atoms to new nuclei which grow into particles at the nanoscale (Ahmed et al., 2016). The chemical synthesis approach massively consumes expensive organic solvents, reducing agents and non-renewable solvents, which leads to environmental pollution. Henceforth, the biological paths of nanoparticle synthesis processes are developing as greener and novel strategies (Sathiyanarayanan et al., 2017).
The Chemical Synthesis of Lipid A
Published in Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison, Endotoxin in Health and Disease, 2020
Shoichi Kusumoto, Koichi Fukase, Masato Oikawa
Recent improved synthetic methods and purification procedures have enabled the synthesis of highly homogeneous compounds in a wide range of scales from a few milligrams up to several grams. In fact, not only standard lipid A but also isotope-labeled lipid A analogs have been prepared. Besides the tritium-labeled derivative described above, 13C-labeled lipid A has also been synthesized recently in the author’s laboratory. A variety of synthetic compounds are expected to open unlimited routes to wide aspects of researches ranging from biology to physics of lipid A and related compounds. The relationship between the chemical structure and biological function is still an important issue but the more precise discussion will be possible hereafter on the reasons for the different biological activities such as the efficiency of transportation, molecular conformations and supramolecular structures of individual compounds. Chemical synthesis is expected to play increasing role in these respects.
Pharmogenology: The Industrial New Drug Development Process
Published in Gary M. Matoren, The Clinical Research Process in the Pharmaceutical Industry, 2020
The use of the more common biologically directed chemical synthesis approach is most likely to result in yet another drug with many properties in common with others already known or being developed in competitive laboratories. This is because of the use of relatively similar batteries of biochemical and pharmacological test systems among contemporary laboratories. New drugs are sometimes discovered by introducing into these same screens compounds (such as the chemical intermediates) whose structures suggest no reason (based on the medicinal chemistry literature) for them to demonstrate the desired biological properties. Indeed, when this happens a novel chemical lead is found and further structural modification may result in a therapeutic agent with some different and possibly more useful properties.
Linkers in fragment-based drug design: an overview of the literature
Published in Expert Opinion on Drug Discovery, 2023
Dylan Grenier, Solène Audebert, Jordane Preto, Jean-François Guichou, Isabelle Krimm
Protein-templated chemical reactions like DCC and KTGS offer a great opportunity to link fragments in a direct manner. First, 3D structures of the protein or the protein-fragment complexes are not essential for the success of the method. Second, chemical synthesis efforts can be more easily streamlined by focusing on generating libraries of fragments containing the reactive functions that will lead to the final compound. However, DCC and KTGS may be limited as both methods use a large amount of target that need to be stable at 25°C or 37°C. As other limitations, hit identification from complex mixtures is often not straightforward whereas other biocompatible reactions might be needed to increase linker diversity. At last, structural knowledge of the target might be required in order to validate the approach with a first proof of concept, before deciding to invest in the synthesis of fragment libraries. As all published cases were based on already known inhibitors, it will be interesting to keep an eye on future strategies involving protein-templated methods applied to de novo lead design.
Improved transfer efficiency of supercharged 36 + GFP protein mediate nucleic acid delivery
Published in Drug Delivery, 2022
Lidan Wang, Jingping Geng, Linlin Chen, Xiangli Guo, Tao Wang, Yanfen Fang, Bonn Belingon, Jiao Wu, Manman Li, Ying Zhan, Wendou Shang, Yingying Wan, Xuemei Feng, Xianghui Li, Hu Wang
Currently, most of medicines on the pharmacies are small chemical molecules, which were manufactured by chemical synthesis. Small molecules are used to treat a wide variety of human diseases and conditions as demonstrated by the increasing approved nucleic therapeutics by the Food and Drug Administration (FDA). For example, insulin used in treating diabetic patients, and the world’s first mRNA vaccine – the COVID-19 vaccines from Pfizer/BioNTech and Moderna are remarkably potent against SARS-Cov-2 infection both utilizing components of nucleic acid therapeutics (Kim et al., 2021; Oliver et al., 2021; Pushparajah et al., 2021). The size, complexity, and stability of biological therapeutic macromolecules can result in highly target specificities compared to small molecule drugs (Zhang et al., 2018). However, the large size of the macromolecules makes them difficult to diffuse into cells, thus resulting in all existing therapeutic biologics target extracellularly and not intracellularly. Therefore, how to deliver bio-macromolecules into target cells and/or subcellular locations of interest is a major challenge ahead in the development of delivery systems.
An overview of late-stage functionalization in today’s drug discovery
Published in Expert Opinion on Drug Discovery, 2019
Michael Moir, Jonathan J. Danon, Tristan A. Reekie, Michael Kassiou
Chemical synthesis is a key enabler in drug discovery. Whether it is the generation of vast libraries of compounds, manipulation of natural products or developing structure-activity relationships from a lead compound, synthesis is an essential step in the drug discovery process. Late-stage diversification has long been the established approach for generating vast libraries of compounds from a common intermediate. Historically, cross coupling of pre-functionalized fragments with various handles has been the major method for diversification. In turn, problems arising from truncated libraries that have generated flat, uninspired compounds have limited the chemical landscape [1]. Late-stage functionalization of C–H bonds offers a tantalizing prospect of diversification, particularly as it includes sp3-carbon atoms, opening up further chemical space. In order for late-stage diversification to be a useful tool for drug discovery, advances in high-throughput technologies and predictive techniques to accelerate biological testing of generated leads are required [2].