Biophysical chemistry最新文献

{"title":"Cationic liposomes as carriers of natural compounds from plant extract","authors":"Claudia Bonechi ,&nbsp;Gabriella Tamasi ,&nbsp;Alessandro Donati ,&nbsp;Flavia Bisozzi ,&nbsp;Michele Baglioni ,&nbsp;Marco Andreassi ,&nbsp;Francesca Ietta ,&nbsp;Gemma Leone ,&nbsp;Agnese Magnani ,&nbsp;Claudio Rossi","doi":"10.1016/j.bpc.2024.107381","DOIUrl":"10.1016/j.bpc.2024.107381","url":null,"abstract":"<div><div>Lipid-based nanocarriers provide versatile platforms for the encapsulation and delivery of many different bioactive compounds to improve the solubility, stability and therapeutic efficacy of bioactive phyto-compounds. In this study, liposomes were used to load leaf extract of <em>Coffea Arabica</em>, which is known to be rich beneficial substances such as alkaloids, flavonoids, etc. The aim of this work is to optimize the valorization of agricultural wastes containing natural antioxidants. The physico-chemical properties of the liposomes loaded with chlorogenic acid or <em>Coffea arabica</em> leaf extract were evaluated. The average size of empty and loaded liposomes was found to range of 120–150 nm, which is consistent with the fact that the addition of chlorogenic acid or <em>Coffea arabica</em> leaf extract can change the average size of the vesicles without affecting the physicochemical properties of the lipid bilayer, which remain stable systems. A structural and morphological characterization as well as an evaluation of biological properties such as viability in normal human dermal fibroblasts, is also been carried out. The cationic liposomes show a good average size and low polydispersity index values, indicating that the liposomes tend to be monodisperse and therefore stable. In particular, DOPC/DOTAP liposomes generally have better properties than DOPC/DDAB liposomes for use as encapsulation systems for natural plant extracts.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"318 ","pages":"Article 107381"},"PeriodicalIF":3.3,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and structural characterization of CB1 receptor antagonists: A comprehensive virtual screening and molecular dynamics study of arachidin-2","authors":"Ana C. Murrieta,&nbsp;Paola Mendoza-Espinosa,&nbsp;José Luis Velasco-Bolom,&nbsp;Flavio F. Contreras-Torres","doi":"10.1016/j.bpc.2024.107385","DOIUrl":"10.1016/j.bpc.2024.107385","url":null,"abstract":"<div><div>The cannabinoid receptor 1 (CB1) is an essential component of the endocannabinoid system, responsible for regulating various physiological processes such as pain, mood, and appetite. Despite increasing interest in the therapeutic potential of CB1 modulators, the precise mechanisms by which small molecules modulate receptor activity—particularly without fully transitioning between active and inactive states—remain partially understood. In this study, the complexity of CB1–ligand interactions was evaluated for the inactive CB1 state. A comprehensive pipeline, integrating ligand-based similarity search, 2D fingerprint-based reverse virtual screening and molecular dynamics (MD) simulations, identified compounds with core scaffolds commonly found in bioactive natural products, such as stilbenoids and polyphenolic compounds. Arachidin-2 (AR2) and a polyphenolic derivative were subjected to extended MD simulations, revealing their ability to stabilize the inactive CB1 state across key helices. The distinct stability differences observed in the helices HI, HIV, and HVI of the active CB1 state further highlighted ligand-specific conformational dynamics. A comparative analysis with co-crystallized synthetic ligands AM6538 and AM841 demonstrated the distinct binding behaviors of natural and synthetic ligands. AR2 showed more favorable binding to the inactive form (−22.0 kcal/mol) than to the active state. Similarly, the polyphenolic compound exhibited a greater binding difference (∼6 kcal/mol) between the inactive and active states. Notably, AM6538 and AM841 demonstrated the strongest binding (∼30 kcal/mol) to the inactive and active state, respectively. Key residues stabilizing the identified compounds in CB1-inactive state included PHE102, GLY166, PHE170, VAL196, LEU359, SER383, and CIS386. These findings underscore the utility of computational methods in the discovery and development of novel CB1 modulators for potential biomedical applications.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"318 ","pages":"Article 107385"},"PeriodicalIF":3.3,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Met58 and di-acidic motif located at C-terminal region of SARS-CoV-2 ORF6 plays a crucial role in its structural conformations","authors":"Prateek Kumar,&nbsp;Kumar Udit Saumya,&nbsp;Taniya Bhardwaj,&nbsp;Rajanish Giri","doi":"10.1016/j.bpc.2024.107384","DOIUrl":"10.1016/j.bpc.2024.107384","url":null,"abstract":"<div><div>Despite being mostly neglected in structural biology, the C-terminal Regions (CTRs) are studied to be multifunctional in humans as well as in viruses. Previously, SARS-CoV-2 Spike and NSP1 proteins' CTRs are observed to be disordered, and experimental evidence showed a gain of structure properties in different physiological environments. In this line, we have investigated the structural dynamics of CTR (residues 38–61) of SARS-CoV-2 ORF6 protein, disrupting bidirectional transport between the nucleus and cytoplasm. ORF6-CTR is disordered in nature but doesn't gain any structure in most conditions. As per studies, residue such as Methionine at 58th position in ORF6 is critical for interaction with Rae1-Nup98. Therefore, along with M58, we have identified a few other mutations from the literature and performed extensive structure modelling and dynamics studies using computational simulations. The exciting revelations in CTR models provide evidence of its structural flexibility and possible capabilities to perform multifunctionality inside the host.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"318 ","pages":"Article 107384"},"PeriodicalIF":3.3,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulating the pH-activity profile of the glucose isomerase from Thermotoga marimita by introducing positively and negatively charged residues","authors":"Weihuan Feng ,&nbsp;Qing Kong ,&nbsp;Xihui Wang ,&nbsp;Ke Zhao ,&nbsp;Chao Lv ,&nbsp;Zengyu Yu","doi":"10.1016/j.bpc.2024.107382","DOIUrl":"10.1016/j.bpc.2024.107382","url":null,"abstract":"<div><div>Glucose isomerase is generally used in the industrial production of high-fructose corn syrup, and a heat- and acid-resistant glucose isomerase is preferred. However, most glucose isomerases exhibit low activity or inactivation at low pH. In this study, we demonstrated that two combination mutants formed by introducing positive and negative charges near the active site and on the surface of the enzyme demonstrated a successful reduction in the optimal pH and increase in the specific activity of glucose isomerase from <em>Thermotoga maritima</em> (TMGI). Thirteen residues, eight surface amino acids and five near the vicinity of active sites, were selected by introducing positively charged residues near the active site (mutant E237R/N298K/N337R) and negatively charged residues at the enzyme surface (mutant R112E/K220E) and were site-mutated on the basis of computational analysis. In mutants E237R/N298K/N337R and R112E/K220E, there was a decrease in the optimal pH of the glucose isomerase from 7.0 to 6.0 and 5.5, respectively, and an increase in the optimal temperature of E237R/N298K/N337R from 95 °C to 100 °C. At pH 5.5 and pH 6.0, the specific activities of R112E/K220E and E237R/N298K/N337R were 2.81 and 1.79 times greater than that of the wild-type enzyme, respectively, and their thermostabilities were greater than that of TMGI. Therefore, these two mutants (E237R/N298K/N337R and R112E/K220E) have great potential for use in the industrial production of high-fructose corn syrup. Moreover, glucose isomerase was expressed in <em>Pichia pastoris</em>, which demonstrated that the high expression and secretion capacity of <em>Pichia pastoris</em> could be used to reduce the production cost of high-fructose corn syrup.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"318 ","pages":"Article 107382"},"PeriodicalIF":3.3,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of the therapeutic potential of novel TIGIT/PVR interaction blockers based advanced computational techniques and experimental validation","authors":"Xudong Lü ,&nbsp;Xiyu Wei ,&nbsp;Chenyu Wang ,&nbsp;Mengjia Tang ,&nbsp;Yuanyuan Jin ,&nbsp;Shuai Fan ,&nbsp;Zhaoyong Yang","doi":"10.1016/j.bpc.2024.107383","DOIUrl":"10.1016/j.bpc.2024.107383","url":null,"abstract":"<div><div>The inhibition of the TIGIT/PVR interaction demonstrates considerable anticancer properties by enhancing the cytotoxic activity of natural killer (NK) and CD8+ T cells. However, the development of small molecule inhibitors that target TIGIT is currently limited. In this study, small molecules with the capacity to bind TIGIT and block the TIGIT/PVR interaction were screened through an advanced computational process, subsequently confirmed by blocking assays. Combined machine learning model XGBOOST and centroid-based molecular docking were employed to expeditiously exclude negative molecules, thereby reducing the chemical space. Subsequently, a blockade assay targeting the TIGIT/PVR interaction was conducted on 14 candidate molecules along with positive control, wherein compound MCULE-5547257859 exhibited the most potent inhibitory effect. Molecular dynamics simulations and binding free energy analyses revealed that compound MCULE-5547257859 possesses a thermodynamically stable conformation, indicative of a stronger binding affinity to TIGIT. In conclusion, our investigation has delineated that compound MCULE-5547257859 effectively impedes the TIGIT/PVR interaction, thereby offering a novel therapeutic modality for oncology.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"318 ","pages":"Article 107383"},"PeriodicalIF":3.3,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural dynamics of a designed peptide pore under an external electric field","authors":"Ai Niitsu ,&nbsp;Jaewoon Jung ,&nbsp;Yuji Sugita","doi":"10.1016/j.bpc.2024.107380","DOIUrl":"10.1016/j.bpc.2024.107380","url":null,"abstract":"<div><div>Membrane potential is essential in biological signaling and homeostasis maintained by voltage-sensitive membrane proteins. Molecular dynamics (MD) simulations incorporating membrane potentials have been extensively used to study the structures and functions of ion channels and protein pores. They can also be beneficial in designing and characterizing artificial ion channels and pores, which will guide further amino acid sequence optimization through comparison between the predicted models and experimental data. In this study, we implemented a uniform external electric field function in the GENESIS MD simulation package to investigate the conformational dynamics of de novo-designed peptide pores. Our simulations and single-channel current recording experiments demonstrate that both charged amino acid residues in the N-terminal sequence of the peptide and the membrane potential are crucial for the structural stability and dynamics of the peptide pores. This suggests that MD simulations with an external electric field enable more accurate screening of designed proteins functioning under membrane potentials, which will ultimately contribute to a deeper understanding of voltage-sensitive membrane proteins from a bottom-up synthetic biology perspective.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"318 ","pages":"Article 107380"},"PeriodicalIF":3.3,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Salvianolic acid B prevents the amyloid transformation of A53T mutant of α-synuclein","authors":"Almas Akhtar,&nbsp;Payal Singh,&nbsp;Nikita Admane,&nbsp;Abhinav Grover","doi":"10.1016/j.bpc.2024.107379","DOIUrl":"10.1016/j.bpc.2024.107379","url":null,"abstract":"<div><div>Parkinson's disease (PD) is a neurodegenerative disorder involving the progressive loss of dopaminergic neurons in the substantia nigra pars compacta triggered by the accumulation of amyloid aggregates of α-synuclein protein. This study investigates the potential of Salvianolic Acid B (Sal<img>B), a water-soluble polyphenol derived from <em>Salvia miltiorrhiza Bunge</em>, in modulating the aggregation of the A53T mutant of α-synuclein (A53T Syn). This mutation is associated with rapid aggregation and a higher rate of protofibril formation in early-onset familial PD. Computational and experimental approaches demonstrated Sal-B effectively prevents the amyloid fibrillation of A53T Syn by interacting with the N-terminal region and NAC domain. Sal-B particularly associates with the KTKEGV motif and NACore segment of A53T Syn by hydrophobic and hydrogen bonding interactions. Replica exchange molecular dynamics (REMD) simulations indicated that Sal-B reduces intramolecular hydrogen bonding and structural transitions into β-sheet rich conformations, thereby lowering the aggregation propensity of A53T Syn. Systematic analysis conducted using biophysical techniques and high-end microscopy has demonstrated significant inhibition in the amyloid transformation of A53T Syn corroborated by a 92 % decrease in ThT maxima at 100 μM Sal-B concentration and microscopic techniques validated the absence of mature fibrillar amyloids. DLS data revealed heterogeneous particle sizes, supporting the formation of smaller unstructured aggregates. These findings underscore Sal-B as a promising therapeutic candidate for PD and related synucleinopathies, warranting further investigation in cellular and animal models to advance potential treatments and early intervention strategies.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"318 ","pages":"Article 107379"},"PeriodicalIF":3.3,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bilirubin: Photophysical and photochemical properties, phototherapy, analytical methods of measurement. A short review","authors":"Alexander S. Tatikolov ,&nbsp;Pavel G. Pronkin ,&nbsp;Ina G. Panova","doi":"10.1016/j.bpc.2024.107378","DOIUrl":"10.1016/j.bpc.2024.107378","url":null,"abstract":"<div><div>Bilirubin, a yellow bile pigment, plays an important role in the body, being a potent antioxidant and having anti-inflammatory, immunomodulatory, cytoprotective, and neuroprotective functions. This makes bilirubin promising as a therapeutic and diagnostic agent in biomedicine. However, excess bilirubin is toxic and should be removed from the body. Bilirubin exhibits photochemical activity, which has been the subject of numerous studies up to now. Such studies are relevant because the bilirubin photochemistry provides the basis for bilirubin removing in phototherapy of neonatal jaundice (neonatal hyperbilirubinemia) and for some therapeutic applications. Furthermore, it can model several elementary processes of molecular photonics. In particular, the bilirubin molecule is capable of ultrafast <em>Z</em>-<em>E</em> photoisomerization and contains two almost identical dipyrromethenone chromophores capable of exciton coupling. The present review considers the data on the photophysical and photochemical properties of bilirubin and ultrafast routes of its phototransformations, as well as its photochemical reactions in phototherapy of neonatal hyperbilirubinemia and the ways to decrease the possible adverse effects of the phototherapy. The main analytical methods of bilirubin measurement in biological systems are also viewed.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"318 ","pages":"Article 107378"},"PeriodicalIF":3.3,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Self-assembling of coiled-coil peptides into virus-like particles: Basic principles, properties, design, and applications with special focus on vaccine design and delivery","authors":"Kisalay Jha ,&nbsp;Puja Jaishwal ,&nbsp;Thakur Prasad Yadav ,&nbsp;Satarudra Prakash Singh","doi":"10.1016/j.bpc.2024.107375","DOIUrl":"10.1016/j.bpc.2024.107375","url":null,"abstract":"<div><div>Self-assembling peptide nanoparticles (SAPN) based delivery systems, including virus-like particles (VLP), have shown great potential for becoming prominent in next-generation vaccine and drug development. The VLP can mimic properties of natural viral capsid in terms of size (20–200 nm), geometry (i.e., icosahedral structures), and the ability to generate a robust immune response (with multivalent epitopes) through activation of innate and/or adaptive immune signals. In this regard, coiled-coil (CC) domains are suitable building blocks for designing VLP because of their programmable interaction specificity, affinity, and well-established sequence-to-structure relationships. Generally, two CC domains with different oligomeric states (trimer and pentamer) are fused to form a monomeric protein through a short, flexible spacer sequence. By using combinations of symmetry axes (2-, 3- and 5- folds) that are unique to the geometry of the desired protein cage, it is possible, in principle, to assemble well-defined protein cages like VLP. In this review, we have discussed the crystallographic rules and the basic principles involved in the design of CC-based VLP. It also explored the functions of numerous noncovalent interactions in generating stable VLP structures, which play a crucial role in improving the properties of vaccine immunogenicity, drug delivery, and 3D cell culturing.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"318 ","pages":"Article 107375"},"PeriodicalIF":3.3,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142823863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of immobilized peroxidase on amino-functionalized magnetic MgFe2O4 nanoparticles for antioxidant activity and decolorization","authors":"Keziban Atacan ,&nbsp;Nuray Güy ,&nbsp;Alican Bahadir Semerci ,&nbsp;Mahmut Özacar","doi":"10.1016/j.bpc.2024.107366","DOIUrl":"10.1016/j.bpc.2024.107366","url":null,"abstract":"<div><div>This investigation aims to immobilize peroxidase onto 3-aminopropyltriethoxysilane (APTES)-functionalized MgFe₂O₄ magnetic nanoparticles to increase enzyme stability, efficiency, and recyclability. The synthesized samples were analyzed using X-ray diffraction, Fourier transform infrared spectroscopy, Thermogravimetric analysis, Vibrating sample magnetometer, and Scanning electron microscopy. The free and immobilized peroxidase were examined against different pH and temperatures as well as storage time and reuse. The immobilized peroxidase maintained 52 % of its initial activity after 10 consecutive measurements thanks to easy magnetic separation. In addition, antioxidant activity was increased by immobilizing the peroxidase to the MgFe₂O₄ magnetic nanoparticles. Congo red dye removal for peroxidase immobilized MgFe₂O₄-APTES was found to be 98.6 % for 240 min. Also, it showed approximately two times more dye decolorization efficiency compared to MgFe₂O₄ and APTES modified MgFe₂O₄. Finally, the immobilized peroxidase was studied by a decolorization study of congo red. So, we believe that the immobilized peroxidase on magnetic nanoparticles reported in this study may be utilized in diverse biotechnology, industrial, and environmental practices.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"318 ","pages":"Article 107366"},"PeriodicalIF":3.3,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142790682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}