Inconspicuous Yet Indispensable: The Coronavirus Spike Transmembrane Domain DOI Open Access
Elena T. Aliper, Roman G. Efremov

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(22), С. 16421 - 16421

Опубликована: Ноя. 16, 2023

Membrane-spanning portions of proteins’ polypeptide chains are commonly known as their transmembrane domains (TMDs). The structural organisation and dynamic behaviour TMDs from proteins various families, be that receptors, ion channels, enzymes etc., have been under scrutiny on the part scientific community for last few decades. reason such attention is that, apart obvious role an “anchor” in ensuring correct orientation protein’s extra-membrane (in most cases functionally important), often actively directly contribute to operation “the protein machine”. They capable transmitting signals across membrane, interacting with adjacent membrane-proximal domains, well ligands, etc. Structural data TMD arrangement still fragmentary at best due complex molecular as, commonly, oligomers, challenges related experimental studies thereof. Inter alia, this especially true viral fusion proteins, which focus numerous quite some time, but provoked unprecedented interest view SARS-CoV-2 pandemic. However, despite structure-centred spike (S) effectuating target cell entry coronaviruses, entire incomplete, whereas segment crucial spike’s fusogenic activity. Therefore, attempting bring together currently available structure dynamics TMDs, present review aims tackle a highly pertinent task better understanding mechanisms underlying virus-mediated fusion, also offering rationale design novel efficacious methods treatment infectious diseases caused by viruses.

Язык: Английский

Biologics, theranostics, and personalized medicine in drug delivery systems DOI Creative Commons
Matteo Puccetti, Marilena Pariano, Aurélie Schoubben

и другие.

Pharmacological Research, Год журнала: 2024, Номер 201, С. 107086 - 107086

Опубликована: Янв. 29, 2024

The progress in human disease treatment can be greatly advanced through the implementation of nanomedicine. This approach involves targeted and cell-specific therapy, controlled drug release, personalized dosage forms, wearable delivery, companion diagnostics. By integrating cutting-edge technologies with delivery systems, greater precision achieved at tissue cellular levels use stimuli-responsive nanoparticles, development electrochemical sensor systems. targeting – by virtue nanotechnology allows for therapy to directed specifically affected tissues while reducing side effects on healthy tissues. As such, nanomedicine has potential transform conditions such as cancer, genetic diseases, chronic illnesses facilitating precise delivery. Additionally, forms devices offer ability tailor unique needs each patient, thereby increasing therapeutic effectiveness compliance. Companion diagnostics further enable efficient monitoring response, enabling customized adjustments plan. question whether all approaches outlined here are viable alternatives current treatments is also discussed. In general, application field biomedicine may provide a strong alternative existing several reasons. this review, we aim present evidence that, although early stages, fully merging technology innovative shows promise successful across various areas, including cancer or diseases.

Язык: Английский

Процитировано

64
Cell-penetrating peptides with nanoparticles hybrid delivery vectors and their uptake pathways DOI
Moataz Dowaidar

Mitochondrion, Год журнала: 2024, Номер 78, С. 101906 - 101906

Опубликована: Май 24, 2024

Язык: Английский

Процитировано

5
Computational Insights into Membrane Disruption by Cell-Penetrating Peptides DOI Creative Commons
Èric Catalina-Hernández, Marcel Aguilella‐Arzo, Alex Perálvarez‐Marín

и другие.

Journal of Chemical Information and Modeling, Год журнала: 2025, Номер unknown

Опубликована: Янв. 17, 2025

Cell-penetrating peptides (CPPs) can translocate into cells without inducing cytotoxicity. The internalization process implies several steps at different time scales ranging from microseconds to minutes. We combine adaptive Steered Molecular Dynamics (aSMD) with conventional (cMD) observe nonequilibrium and equilibrium states study the early mechanisms of peptide–bilayer interaction leading CPPs internalization. define three membrane compositions representing bilayer sections, neutral lipids (i.e., upper leaflet), cholesterol hydrophobic core), neutral/negatively charged lower leaflet) energy barriers disruption Arg9, MAP, TP2, cationic, amphiphilic, CPPs, respectively. Cholesterol negatively increase energetic for crossing. TP2 interacts by insertion, while Arg9 disrupts forming transient or stable pores. MAP has shown both behaviors. Collectively, these findings underscore significance innovative computational approaches in studying membrane-disruptive and, more specifically, harnessing their potential cell penetration.

Язык: Английский

Процитировано

0
Physicochemical and biochemical characterization of antimicrobial peptides DOI
Valentina Quezada,

Paula Guzmán-Satoque,

María Camila Rincón-Garcia

и другие.

Elsevier eBooks, Год журнала: 2025, Номер unknown, С. 259 - 299

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0
The Emerging Roles of γ-Glutamyl Peptides Produced by γ-Glutamyltransferase and the Glutathione Synthesis System DOI Creative Commons
Yoshitaka Ikeda, Junichi Fujii

Cells, Год журнала: 2023, Номер 12(24), С. 2831 - 2831

Опубликована: Дек. 13, 2023

L-γ-Glutamyl-L-cysteinyl-glycine is commonly referred to as glutathione (GSH); this ubiquitous thiol plays essential roles in animal life. Conjugation and electron donation enzymes such peroxidase (GPX) are prominent functions of GSH. Cellular balance robustly maintained via regulated synthesis, which catalyzed the coordination γ-glutamyl-cysteine synthetase (γ-GCS) synthetase, well by reductive recycling reductase. A prevailing short supply L-cysteine (Cys) tends limit leads production various other γ-glutamyl peptides due unique enzymatic properties γ-GCS. Extracellular degradation γ-glutamyltransferase (GGT) a dominant source Cys for some cells. GGT catalyzes hydrolytic removal group or transfers it amino acids dipeptides outside Such processes depend on an abundance acceptor substrates. However, physiological extracellularly preserved have long been unclear. The identification peptides, glutathione, allosteric modulators calcium-sensing receptors (CaSRs) could provide insights into significance preservation peptides. It conceivable that generate new class intercellular messaging molecules response extracellular microenvironments.

Язык: Английский

Процитировано

12
Look Beyond Plasma Membrane Biophysics: Revealing Considerable Variability of the Dipole Potential Between Plasma and Organelle Membranes of Living Cells DOI Open Access
Máté Szabó, Bence Cs. Szabo,

Kitti Kurtan

и другие.

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(3), С. 889 - 889

Опубликована: Янв. 22, 2025

Due to the lack of measurement techniques suitable for examining compartments intact, living cells, membrane biophysics is almost exclusively investigated in plasma despite fact that its alterations intracellular organelles may also contribute disease pathogenesis. Here, we employ a novel, easy-to-use, confocal microscopy-based approach utilizing F66, an environment-sensitive fluorophore combination with fluorescent organelle markers and quantitative image analysis determine magnitude molecular order-related dipole potential various tumor neural cell lines. Our comparative demonstrates considerable variations be large enough modulate protein functions, inward decreasing gradient on route secretory/endocytic pathway (plasma >> lysosome > Golgi endoplasmic reticulum), whereas mitochondrial membranes are characterized by slightly larger than lysosomes. sensitive quantify biophysical properties selectively their and, therefore, identify affected therapeutic targets diseases associated lipid composition thus such as tumors, metabolic, neurodegenerative, or lysosomal storage disorders.

Язык: Английский

Процитировано

0
Exosomes: A Promising Drug Delivery Tool in Hepatic Drug Delivery DOI
Neha Kanojia,

Komal Thapa,

Thakur Gurjeet Singh

и другие.

Journal of Drug Delivery Science and Technology, Год журнала: 2025, Номер unknown, С. 106761 - 106761

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
Novel insights into the modulation of the voltage-gated potassium channel KV1.3 activation gating by membrane ceramides DOI Creative Commons
Bence Cs. Szabo, Máté Szabó, Péter Nagy

и другие.

Journal of Lipid Research, Год журнала: 2024, Номер 65(8), С. 100596 - 100596

Опубликована: Июль 15, 2024

Язык: Английский

Процитировано

2
GraphCPP: The new state‐of‐the‐art method for cell‐penetrating peptide prediction via graph neural networks DOI Creative Commons
Attila Imre, Balázs Balogh, István M. Mándity

и другие.

British Journal of Pharmacology, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 20, 2024

Background and Purpose Cell‐penetrating peptides (CPPs) are short amino acid sequences that can penetrate cell membranes deliver molecules into cells. Several models have been developed for their discovery, yet these often face challenges in accurately predicting membrane penetration due to the complex nature of peptide–cell interactions. Hence, there is a need innovative approaches enhance predictive performance. Experimental Approach In this study, we present application GraphCPP, novel graph neural network (GNN) prediction capability peptides. Key Results A new comprehensive dataset—dubbed CPP1708—was constructed resulting largest reliable database CPPs date. Comparative analyses with previous methods, such as MLCPP2, C2Pred, CellPPD CellPPD‐Mod, demonstrated superior performance our model. Upon testing against other published GraphCPP performs exceptionally, achieving 0.5787 Matthews correlation coefficient 0.8459 area under curve (AUC) values on one dataset. This means 92.8% 23.3% improvement AUC measures respectively compared next best The model effectively learn peptide representations was through t‐distributed stochastic neighbour embedding plots. Additionally, uncertainty analysis revealed maintains high confidence predictions shorter than 40 acids. source code available at https://github.com/attilaimre99/GraphCPP . Conclusion Implications These findings indicate potential GNN‐based improve CPP it may contribute towards development more efficient drug delivery systems.

Язык: Английский

Процитировано

2
Chemical strategies for antisense antibiotics DOI Creative Commons
Mathijs Pals,

Alf A. Lindberg,

Willem A. Velema

и другие.

Chemical Society Reviews, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

Antibacterial resistance is a severe threat to modern medicine and human health. Antisense technology offers an attractive modality for future antibiotics.

Язык: Английский

Процитировано

1