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Application of Bioresponsive Polymers in Gene Delivery
Published in Deepa H. Patel, Bioresponsive Polymers, 2020
Tamgue Serges William, Drashti Pathak, Deepa H. Patel
They undergo the mechanism of protonation when they are present in acidic medium. These polymers can be from natural origin (albumin, gelatin, chitosan (CS)), or synthetics examples include poly(L-lysine) (PLL), polyethyleneimine (PEI), Polyaspartamide (PAsp) and poly(N,N-diakylaminoethyl methacrylates) (PDAAEMA).
Acceleration of Chemical Reactions by Catalysts: A Wonder of the Natural World
Published in John R. Helliwell, The Whats of a Scientific Life, 2019
The understanding of how an enzyme works is transformed when its three-dimensional structure is determined by X-ray crystallography. The first such study was by a research team based at The Royal Institution in London led by Dr David Phillips in the early 1960s. Figure 12.2 shows a model of the structure of this enzyme, lysozyme, which breaks a bond in a bacterial cell wall. Why is it so called? Such a chemical breaking process is known as ‘lysis’ and so this enzyme became known as ‘lysozyme’. The view direction in Figure 12.2 (top) shows the large cleft where the enzyme binds onto the bacterium. It is in the cleft that two reactive amino acids of the lysozyme sit waiting to do their chemical catalysis work. These are the amino acid residues aspartic acid 52 and glutamic acid 35 (Figures 12.2 middle and bottom, i.e. zooming in). They reside on either side of the chemical bond in the bacterial cell wall that is to be broken. Their protonation states (the presence or absence of a hydrogen) of their side chains determines their reactivities, one being protonated (glutamic acid 35) and the other not. After the chemical reaction, the protonation of glutamic acid is replenished by a proton in the water of which there are many available.
Structural Aspects of Luteinizing Hormone Actions
Published in Mario Ascoli, Luteinizing Hormone Action and Receptors, 2019
Wayne L. Gordon, Darrell N. Ward
The imidazole group on histidine has a pK. in proteins in the range 6.5 to 7.1; thus it is one of the few functional groups that may actually change its degree of protonation under physiological conditions. For this reason it may be subject to useful physiological modulation as, for example, in enzyme active sites. Among the lutropin molecules, only two histidine residues are invariant, and these are at positions 83 and 94 on the α-subunit (Figure 1). The histidine at residue 87 on this subunit is present in all but the equine α-subunit, where there is a tyrosine-histidine transposition between positions 87 and 93.79
New cyclopentaquinoline and 3,5-dichlorobenzoic acid hybrids with neuroprotection against oxidative stress for the treatment of Alzheimer’s disease
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Kamila Czarnecka, Małgorzata Girek, Paweł Kręcisz, Robert Skibiński, Kamil Łątka, Jakub Jończyk, Marek Bajda, Piotr Szymczyk, Grzegorz Galita, Jacek Kabziński, Ireneusz Majsterek, Alba Espargaró, Raimon Sabate, Paweł Szymański
Corina online (Molecular Networks and Altamira) was used to create three-dimensional structures of compounds, that were then prepared using Sybyl 8.0 (Tripos). Protonation states were inspected, hydrogen atoms were added, atom types were checked and Gesteiger-Marsili charges were assigned. All ligands were docked to acetylcholinesterase from 2CKM and to butyrylcholinesterase based on a 1P0I crystal structure using GoldSuite 5.1 (CCDC). Before docking, the proteins were prepared in the following way: all histidine residues were protonated at Nε, the hydrogen atoms were added, ligand and water molecules were removed; the binding site was defined as all amino acid residues within 10 Å from bis-(7)-tacrine for AChE, and 20 Å from the glycerol molecule for BuChE. A standard set of genetic algorithms with a population size of 100, number of operations 100 000, and clustering with a tolerance of 1 Å was applied. After docking process, 10 ligand poses, sorted by GoldScore (for AChE) and ChemScore (for BuChE) were obtained. The results were visualised by PyMOL 0.99rc6 (DeLano Scientific LLC).
Design and synthesis of novel quinazolinone-based derivatives as EGFR inhibitors with antitumor activity
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Amr Sonousi, Rasha A. Hassan, Eman O. Osman, Amr M. Abdou, Soha H. Emam
The crystallographic structure of EGFR protein (PDB: 1M17) was obtained from the protein data bank website, (http://www.pdb.org) with resolution of 2.60 Å. All the molecular modelling studies were carried out using Molecular Operating Environment (MOE 2020.09; Chemical Computing Group, Canada) as the computational software. The hydrogen atoms were added, the protonation states of the amino acid residues were assigned, and the partial charges of atoms were added using Protonate 3D algorithm. Compounds were modelled using MOE builder, and the structure was energy minimised using the MMFF94x force field. Using the MOE induced-fit Dock tool, docking studies of the synthesised compound into the active site was done and the final docked complexes of ligand–enzyme was selected according to the criteria of binding energy score combined with geometrical matching quality.
Anastrozole and related glucuronic acid conjugate are electrophilic species
Published in Xenobiotica, 2022
Siyu Ding, Siyu Liu, Yaxuan Chen, Ying Peng, Jiang Zheng
Surprisingly, the ANA-derived GSH conjugate was also detected in the incubation mixture containing ANA, GSH and a buffer system. The observed spontaneous GSH conjugation suggests that ANA itself is an electrophilic species. Additionally, proton concentration (pH) was found to dramatically alter the rate of the reaction. Specifically, the efficiency of the spontaneous conjugation increased with the increase of pH value of the incubation system. The deprotonation (pH 10) of the sulfhydryl group facilitated the conjugation reaction, while the protonation (pH 4) proceeded in the opposite way. It may explain that the deprotonation by alkaline resulted in the development of sulfhydryl anion which is much more nucleophilic than free thiol group. The elevation of nucleophilicity accelerated the substitution reaction.