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Methods in molecular exercise physiology
Published in Adam P. Sharples, James P. Morton, Henning Wackerhage, Molecular Exercise Physiology, 2022
Adam P. Sharples, Daniel C. Turner, Stephen Roth, Robert A. Seaborne, Brendan Egan, Mark Viggars, Jonathan C. Jarvis, Daniel J. Owens, Jatin G. Burniston, Piotr P. Gorski, Claire E. Stewart
A method known as SDS-polyacrylamide gel electrophoresis (SDS-PAGE) is then used to separate the denatured and negatively charged proteins within each sample by passing the samples through a gel constructed from acrylamide polymers, which cross-link to form a molecular sieve. Samples containing the standardised protein concentrations are loaded into wells at the top of the gel and an electric current is passed through the gel. This causes the negatively charged proteins to migrate towards the positive electrode at the bottom of the gel. Small proteins pass through the gel faster than large proteins and thus the procedure effectively orders proteins according to their size, i.e. their molecular weight in kDa (Figure 2.9).
Vaccine Adjuvants in Immunotoxicology
Published in Mesut Karahan, Synthetic Peptide Vaccine Models, 2021
Many cytokines are tried to be used as adjuvants because they stimulate the immune system. These small proteins play an important role in cell signaling, induction, and direction of cellular and humoral immune responses, and promote antibody production (Kishimoto, Taga, and Akira 1994). It was suggested that they increased the immune response following the use of various cytokines such as interferon (IFN-α, IFN-γ) and interleukin (IL-2, IL-12, IL-15, IL-18, IL-21) as adjuvants (Spickler and Roth 2003). However, they have stability problems due to their protein structure, and their half-life is short. Their areas of use are limited as they all show dose-dependent toxicity (especially hepatotoxicity and CYP-dependent drug interactions) (Yurdakök and İnce 2008).
Antiviral Agents and Rational Drug Design
Published in Nathan Keighley, Miraculous Medicines and the Chemistry of Drug Design, 2020
The HIV protease enzyme is an aspartyl protease, which contains an aspartic acid residue in the active site, which is crucial for the catalytic cleavage of peptide bonds. The enzyme is a relatively small protein that can be readily made by synthetic techniques or by cloning and expression in rapidly dividing cells, then isolated and purified in large quantities. Crystallisation of HIV protease is relatively straightforward, hence this enzyme is an ideal target for rational structure-based drug design. From x-ray crystallographic studies, novel inhibiters can be developed to produce promising lead compounds.
Molecular docking studies, anti-Alzheimer’s disease, antidiabetic, and anti-acute myeloid leukemia potentials of narcissoside
Published in Archives of Physiology and Biochemistry, 2023
Tingting Liu, Lixia Cao, Tingting Zhang, Huan Fu
Firstly, it was used from Gaussian software program (Frisch et al.2009) to obtain optimised structures of molecules, which created files with *.sdf extension using these structures. Using these files, all calculations were made with Maestro Molecular modelling platform (version 12.2) by Schrödinger, LLC (2019a). Maestro Molecular modelling platform (version 12.2) by Schrödinger comes together from many modules. In the first module used, the protein preparation module (Friesner et al.2006, Schrödinger 2019b) was used for the preparation of proteins. There are many small proteins in the enzymes studied. The crystal structures of these proteins have been downloaded from the protein data bank site. These enzymes were initially minimised and the water molecules in the structure were removed. In the next step, the active sites of the enzymes were determined, in which the proteins in this active zone were given freedom of movement. Therefore, these proteins were enabled to interact with molecules more easily. In the next step, the molecule was prepared for calculations, the LigPrep module (Sastry et al.2013, Schrödinger 2019c) was used for this process.
Investigational systemic drugs for moderate to severe plaque psoriasis: What’s new?
Published in Expert Opinion on Investigational Drugs, 2023
Laura Calabrese, Dalma Malvaso, Flaminia Antonelli, Maria Mannino, Ketty Peris, Andrea Chiricozzi
Considering all limitations of currently approved biological drugs, it can be perceived how the development of new therapeutic strategies should be encouraged. For instance, the development of nanobodies, such as sonelokimab, could hold considerable advantages. Indeed, these drugs have the potential to combine the strength of small proteins with the properties of monoclonal antibodies. Sonelokimab, similarly to bimekizumab, can target both IL-17A and F, thus blocking one of the most crucial pathways in psoriasis pathogenesis. Bimekizumab and sonelokimab neutralize IL-17A/F, although the first is a mAb and the second a nanobody. Dual neutralization of IL-17A and IL-17 F has indeed shown in vitro a greater suppression of inflammation compared with IL-17A inhibition alone [99]. On the other hand, due to its smaller size and its molecular nature, sonelokimab is likely to have better tissue penetration and a reduced propensity to immunogenicity, compared to the currently available biologic agents. For these reasons, this new class of agents may hold the promise to enrich the current therapeutic scenario of psoriasis.
Bioanalytical strategies in drug discovery and development
Published in Drug Metabolism Reviews, 2021
Aarzoo Thakur, Zhiyuan Tan, Tsubasa Kameyama, Eman El-Khateeb, Shakti Nagpal, Stephanie Malone, Rohitash Jamwal, Chukwunonso K. Nwabufo
For large molecules, sample clean-up/additional sample preparation procedures are generally needed to clean up complex biological matrixes and are used in conjugation with other sample processing techniques described above. In cases of small proteins and small peptides (<10,000Da), these additional sample preparation techniques are often sufficient. These clean-up/additional sample preparation procedures can include MWCO ultrafiltration, PPT, LLE, or SPE. The type of sample clean-up procedure/additional sample preparation procedures used depends on various factors, such as the size of the molecule, mass spectrometry signal suppression, possibility of diluting out interferences, presence of detergents in the sample, etc. Even though some of these additional sample preparation procedures can result in more time and cost, technology is moving toward a microenvironment for procedures, such as LLE and SPE, to aid in reducing the number of solvents and material needed as well as for its utility in automation (Soltani and Jouyban 2014).