Biophysical chemistry最新文献_第2页

Bilirubin nanotechnology: An innovative approach in biomedicine

IF 3.3 3区生物学

Biophysical chemistry Pub Date : 2025-02-12 DOI: 10.1016/j.bpc.2025.107412

Alexander S. Tatikolov , Pavel G. Pronkin , Ina G. Panova

{"title":"Bilirubin nanotechnology: An innovative approach in biomedicine","authors":"Alexander S. Tatikolov , Pavel G. Pronkin , Ina G. Panova","doi":"10.1016/j.bpc.2025.107412","DOIUrl":"10.1016/j.bpc.2025.107412","url":null,"abstract":"<div><div>Bilirubin, a product of heme catabolism, is toxic at elevated concentrations (>250–300 μM in blood serum), whereas at therapeutic concentrations (∼20–200 μM) exerts potent antioxidant, anti-inflammatory, immunomodulatory, cytoprotective and neuroprotective effects. Despite the therapeutic potential, its use in clinical practice is hampered by poor aqueous solubility, instability, and rapid metabolism. Nanotechnology overcomes these limitations and additionally imparts to bilirubin the advantages characteristic of nanopreparations: targeted action on the desired organ/tissue, increased therapeutic efficacy by delaying drug elimination from the body, improved transportation over biological barriers, the ability to combine therapeutic and diagnostic properties in a single agent. The review analyses the chemical synthesis, therapeutic mechanisms, and preclinical applications of nanosystems comprising bilirubin. In particular, nanostructures obtained by the covalent binding of bilirubin to macromolecules, bilirubin encapsulation in nanocarriers, bilirubin conjugation with metal nanoparticles and nanofunctionalization of inorganic compounds are considered; the data on the therapeutic trials of nanobilirubin are summarized. While studies on animal models and in vitro systems demonstrate improved biodistribution, reduced toxicity, and enhanced efficacy, no clinical trials to date have validated nanobilirubin formulations. Key barriers may include unresolved challenges in scalable synthesis, long-term biocompatibility, reproducible dosing of nanoformulations. Hence, further development of nanotherapeutic bilirubin agents for clinical practice is urgent.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"320 ","pages":"Article 107412"},"PeriodicalIF":3.3,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143429135","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}

引用次数: 0

On the thermal and chemical stability of DNAJB6b and its globular domains

IF 3.3 3区生物学

Biophysical chemistry Pub Date : 2025-02-03 DOI: 10.1016/j.bpc.2025.107401

Celia Fricke , Jelica Milošević , Andreas Carlsson , Lars Boyens-Thiele , Marija Dubackic , Ulf Olsson , Alexander K. Buell , Sara Linse

{"title":"On the thermal and chemical stability of DNAJB6b and its globular domains","authors":"Celia Fricke , Jelica Milošević , Andreas Carlsson , Lars Boyens-Thiele , Marija Dubackic , Ulf Olsson , Alexander K. Buell , Sara Linse","doi":"10.1016/j.bpc.2025.107401","DOIUrl":"10.1016/j.bpc.2025.107401","url":null,"abstract":"<div><div>The chaperone DNAJB6b (JB6) plays important roles in increasing amyloid protein solubility and inhibiting amyloid fibril formation, a causative factor for neurodegenerative diseases like Alzheimer's and Parkinson's disease. Insights into the biophysical properties of JB6, including its structure, self-assembly and stability towards denaturation, may enhance the understanding of the physicochemical basis of chaperone action. However, many of the biophysical properties of the chaperone remain elusive. Here, we investigated the structure and stability of JB6 and its domains towards thermal and chemical denaturation using Fourier transform infrared and circular dichroism spectroscopy to examine the thermodynamic properties. Both domains act as independent folding units. We find that the N-terminal domain (NTD) of JB6 is more stable than its C-terminal domain (CTD). Both domains are stabilized in the context of the full-length protein. The intact protein unfolds in a step-wise manner when subjected to a denaturing agent with the CTD unfolding at a lower denaturant concentration than the NTD. The combination of thermal and chemical denaturation followed by differential scanning fluorimetry revealed the enthalpy changes (22.6 and 26.4 kJ mol<sup>−1</sup>) and heat capacity changes (2.8 and 3.0 kJ/(mol*K)) upon denaturation of NTD alone and of NTD within the full-length protein, respectively. The understanding of JB6's biophysical properties complements the increasing amount of data on JB6's interactions with client proteins, paving the way for further investigation of the mechanism of its cellular function.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"320 ","pages":"Article 107401"},"PeriodicalIF":3.3,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143379129","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}

引用次数: 0

Discovery of the potential of cholesterol-lowering human CYP7 enzymes as biocatalysts for the production of C7 hydroxylated steroids

IF 3.3 3区生物学

Biophysical chemistry Pub Date : 2025-01-26 DOI: 10.1016/j.bpc.2025.107393

Yaraslau Dzichenka , Michail Shapira , Antos Sachanka , Tatsiana Cherkesova , Veronika Shchur , Ljubica Grbović , Ksenija Pavlović , Bojana Vasiljević , Marina Savić , Andrea Nikolić , Aleksandar Oklješa , Jovana Ajduković , Ivana Kuzminac , Aliaksei Yantsevich , Sergey Usanov , Suzana Jovanović-Šanta

{"title":"Discovery of the potential of cholesterol-lowering human CYP7 enzymes as biocatalysts for the production of C7 hydroxylated steroids","authors":"Yaraslau Dzichenka , Michail Shapira , Antos Sachanka , Tatsiana Cherkesova , Veronika Shchur , Ljubica Grbović , Ksenija Pavlović , Bojana Vasiljević , Marina Savić , Andrea Nikolić , Aleksandar Oklješa , Jovana Ajduković , Ivana Kuzminac , Aliaksei Yantsevich , Sergey Usanov , Suzana Jovanović-Šanta","doi":"10.1016/j.bpc.2025.107393","DOIUrl":"10.1016/j.bpc.2025.107393","url":null,"abstract":"<div><div>Steroidal C7 alcohols and their esters are perspective agents in drug discovery. In addition, hydroxylation at C7 position could allow further modification of steroidal moiety. Such transformation is performed easily by the enzymes. Human steroid 7α-hydroxylases CYP7A1 and CYP7B1 are key enzymes taking part in the biotransformation of cholestanes, androstanes, pregnanes. In the article, we are focusing on the results of <em>in vitro</em> screening of a library of modified steroids toward CYP7 enzymes. A couple of compounds were found to express the affinity for binding to the enzymes, comparable with corresponding values for CYP7 natural ligands. Among them are 17-substituted androstane derivatives with N-containing pyridine ring and enone derivative of lithocholic acid, which bound by human CYP7A1, and D-seco and C16 oxime androstanes, which were identified as novel CYP7B1 ligands. Screening results revealed that both enzymes bind with high affinity a well-known drug abiraterone: in the case of CYP7A1 substrate-like binding mode was detected, with the formation of monohydroxylated product, while in case of CYP7B1 inhibitor-like binding was observed. Since CYP7 enzymes convert some of the studied compounds into their 7-hydroxy derivatives, potential of these enzymes as perspective regio- and stereoselective biocatalysts for obtaining C7 hydroxylated steroids could be assumed.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"319 ","pages":"Article 107393"},"PeriodicalIF":3.3,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143144407","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}

引用次数: 0

Molecular dynamics study on clustered DNA damage: AP sites on the same strand

IF 3.3 3区生物学

Biophysical chemistry Pub Date : 2025-01-25 DOI: 10.1016/j.bpc.2025.107394

Kazushi Terakawa , Susumu Fujiwara , Tomoko Mizuguchi , Hiroaki Nakamura , Ken Akamatsu , Naoya Shikazono , Yoshiteru Yonetani

引用次数: 0

SPR is a fast and straightforward method to estimate the binding constants of cyclic dinucleotides to their binding partners, such as STING or poxin

IF 3.3 3区生物学

Biophysical chemistry Pub Date : 2025-01-20 DOI: 10.1016/j.bpc.2025.107392

Hagen Sülzen, Martin Klima, Vojtech Duchoslav, Evzen Boura

{"title":"SPR is a fast and straightforward method to estimate the binding constants of cyclic dinucleotides to their binding partners, such as STING or poxin","authors":"Hagen Sülzen, Martin Klima, Vojtech Duchoslav, Evzen Boura","doi":"10.1016/j.bpc.2025.107392","DOIUrl":"10.1016/j.bpc.2025.107392","url":null,"abstract":"<div><div>The development of small molecule drugs that target protein binders is the central goal in medicinal chemistry. During the lead compound development process, hundreds or even thousands of compounds are synthesized, with the primary focus on their binding affinity to protein targets. Typically, IC<sub>50</sub> or EC<sub>50</sub> values are used to rank these compounds. While thermodynamic values, such as the dissociation constant (KD), would be more informative, they are experimentally less accessible. In this study, we compare isothermal calorimetry (ITC) with surface plasmon resonance (SPR) using human STING, a key protein of innate immunity, and several cyclic dinucleotides (CDNs) that serve as its ligands. We demonstrate that SPR, with recent technological advancements, provides KDs that are sufficiently accurate for drug development purposes. To illustrate the versatility of our approach, we also used SPR to estimate the KD of poxin binding to cyclic GMP-AMP (cGAMP) that serves as a second messenger in the innate immune system. In conclusion, SPR offers a high benefit-to-cost ratio, making it an effective tool in the drug design process.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"319 ","pages":"Article 107392"},"PeriodicalIF":3.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027809","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}

引用次数: 0

Mapping conformational landscape in protein folding: Benchmarking dimensionality reduction and clustering techniques on the Trp-Cage mini-protein

IF 3.3 3区生物学

Biophysical chemistry Pub Date : 2025-01-17 DOI: 10.1016/j.bpc.2025.107389

Sayari Bhattacharya, Suman Chakrabarty

{"title":"Mapping conformational landscape in protein folding: Benchmarking dimensionality reduction and clustering techniques on the Trp-Cage mini-protein","authors":"Sayari Bhattacharya, Suman Chakrabarty","doi":"10.1016/j.bpc.2025.107389","DOIUrl":"10.1016/j.bpc.2025.107389","url":null,"abstract":"<div><div>Quantitative characterization of protein conformational landscapes is a computationally challenging task due to their high dimensionality and inherent complexity. In this study, we systematically benchmark several widely used dimensionality reduction and clustering methods to analyze the conformational states of the Trp-Cage mini-protein, a model system with well-documented folding dynamics. Dimensionality reduction techniques, including Principal Component Analysis (PCA), Time-lagged Independent Component Analysis (TICA), and Variational Autoencoders (VAE), were employed to project the high-dimensional free energy landscape onto 2D spaces for visualization. Additionally, clustering methods such as K-means, hierarchical clustering, HDBSCAN, and Gaussian Mixture Models (GMM) were used to identify discrete conformational states directly in the high-dimensional space. Our findings reveal that density-based clustering approaches, particularly HDBSCAN, provide physically meaningful representations of free energy minima. While highlighting the strengths and limitations of each method, our study underscores that no single technique is universally optimal for capturing the complex folding pathways, emphasizing the necessity for careful selection and interpretation of computational methods in biomolecular simulations. These insights will contribute to refining the available tools for analyzing protein conformational landscapes, enabling a deeper understanding of folding mechanisms and intermediate states.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"319 ","pages":"Article 107389"},"PeriodicalIF":3.3,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036684","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}

引用次数: 0

The role of nonlinear axonal membrane capacitance in modulating ion channel cooperativity in action potential dynamics: Studies on Hodgkin-Huxley's model

IF 3.3 3区生物学

Biophysical chemistry Pub Date : 2025-01-11 DOI: 10.1016/j.bpc.2025.107391

Jitender Kumar , Patrick Das Gupta , Subhendu Ghosh

引用次数: 0

Nano-viscosimetry analysis of membrane disrupting peptide magainin2 interactions with model membranes 膜干扰肽magainin2与模型膜相互作用的纳米粘度分析。

IF 3.3 3区生物学

Biophysical chemistry Pub Date : 2025-01-10 DOI: 10.1016/j.bpc.2025.107390

Sara Pandidan, Adam Mechler

{"title":"Nano-viscosimetry analysis of membrane disrupting peptide magainin2 interactions with model membranes","authors":"Sara Pandidan, Adam Mechler","doi":"10.1016/j.bpc.2025.107390","DOIUrl":"10.1016/j.bpc.2025.107390","url":null,"abstract":"<div><div>The rapid spread of antibiotic-resistant strains of bacteria has created an urgent need for new alternative antibiotic agents. Membrane disrupting antimicrobial peptides (AMPs): short amino acid sequences with bactericidal and fungicidal activity that kill pathogens by permeabilizing their plasma membrane may offer a solution for this global health crisis. Magainin 2 is an AMP secreted by the African clawed frog (<em>Xenopus laevis</em>) that is described as a toroidal pore former membrane disrupting AMP. Magainin 2 is one of the most thoroughly studied AMPs, yet its mechanism of action is still largely hypothetical: visual evidence of the pore formation is lacking, and the molecular mechanism leading to pore formation is still debated. In the present study, quartz crystal microbalance (QCM) based viscoelastic fingerprinting analysis supported by dye leakage experiments and atomic force microscopy (AFM) imaging was used to glean deeper insights into the mechanism of action. The effect of membrane charge, acyl chain unsaturation and cholesterol concentration were also investigated. The results show lipid specific disruptive mechanism of magainin 2. QCM nano-viscometry measurements revealed the presence of distinct stages in the mechanism of magainin 2 action that, with dye leakage data, confirm the existence of an initial transient pore stage that may result in peptide flip-flop between the outer and inner membrane leaflets. There is evidence of a further mechanistic stage at high peptide concentrations that is consistent with membrane collapse into a peptide-lipid mixed phase that is distinct from the transient pore formation. The results confirm some of the earliest hypotheses about magainin 2 action, while also highlighting the membrane modulating effect of this peptide.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"318 ","pages":"Article 107390"},"PeriodicalIF":3.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969550","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}

引用次数: 0

Molecular dynamics of SARS-CoV-2 omicron variants from Philippine isolates against hesperidin as spike protein inhibitor 菲律宾分离株抗刺突蛋白抑制剂橙皮苷的SARS-CoV-2组粒变异的分子动力学

IF 3.3 3区生物学

Biophysical chemistry Pub Date : 2024-12-30 DOI: 10.1016/j.bpc.2024.107387

June Alexis A. Santos , Searle S. Duay

{"title":"Molecular dynamics of SARS-CoV-2 omicron variants from Philippine isolates against hesperidin as spike protein inhibitor","authors":"June Alexis A. Santos , Searle S. Duay","doi":"10.1016/j.bpc.2024.107387","DOIUrl":"10.1016/j.bpc.2024.107387","url":null,"abstract":"<div><div>SARS-CoV-2 remains a global threat with new sublineages posing challenges, particularly in the Philippines. Hesperidin (HD) is being studied as a potential prophylactic for COVID-19. However, the virus's rapid evolution could alter how HD binds to it, affecting its effectiveness. Here, we study the mutation-induced variabilities of HD dynamics and their effects on molecular energetics in SARS-CoV-2 spike receptor complex systems. We considered eight different point mutations present in the Omicron variant. Root-mean-square deviation and binding energy analysis showed that S477N and Omicron did not eject HD throughout the simulation. Hydrogen bond distribution analysis highlighted the involvement of hydrogen bonding in mutant-HD stabilization, especially for S477N and Omicron. Root-mean-square fluctuation analysis revealed evidence of Y505H destabilization on complex systems, while distal-end loop mutations increased loop flexibility for all models bearing the three mutations. Per-residue energy decomposition demonstrated that Q493R substitution increased HD interaction. Free energy landscape and essential dynamics through principal component analysis provided insights into the conformational subspace distribution of mutant model molecular dynamics trajectories. In conclusion, significant mutations contributed to the HD interaction in different ways. S477N has shown significant binding contributions through favorable ligand interaction, while other mutations contribute via conformational modifications, increased affinity due to sidechain mutations, and increased loop flexibility.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"318 ","pages":"Article 107387"},"PeriodicalIF":3.3,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913828","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}

引用次数: 0

Macromolecular interaction mechanism of the bacteriocin EntDD14 with the receptor binding domain (RBD) for the inhibition of SARS-CoV-2 and the JN.1 variant: Biomedical study based on elastic networks, stochastic Markov models, and macromolecular volumetric analysis

IF 3.3 3区生物学

Biophysical chemistry Pub Date : 2024-12-29 DOI: 10.1016/j.bpc.2024.107388

Luis Moncayo Molina , María Erlinda Aguaiza Pichazaca , José Isidro Yamasqui Padilla , María Eufemia Pinos Calle , Karla Maribel Yamasqui Pinos , Arlene Cardozo Urdaneta , Carla Lossada , Yovani Marrero-Ponce , Felix Martinez-Rios , Ysaías J. Alvarado , Aleivi Pérez , Lenin González-Paz

{"title":"Macromolecular interaction mechanism of the bacteriocin EntDD14 with the receptor binding domain (RBD) for the inhibition of SARS-CoV-2 and the JN.1 variant: Biomedical study based on elastic networks, stochastic Markov models, and macromolecular volumetric analysis","authors":"Luis Moncayo Molina , María Erlinda Aguaiza Pichazaca , José Isidro Yamasqui Padilla , María Eufemia Pinos Calle , Karla Maribel Yamasqui Pinos , Arlene Cardozo Urdaneta , Carla Lossada , Yovani Marrero-Ponce , Felix Martinez-Rios , Ysaías J. Alvarado , Aleivi Pérez , Lenin González-Paz","doi":"10.1016/j.bpc.2024.107388","DOIUrl":"10.1016/j.bpc.2024.107388","url":null,"abstract":"<div><div>Bacteriocins, a class of molecules produced by bacteria, exhibit potent antimicrobial properties, including antiviral activities. The urgent need for treatments against SARS-CoV-2 has proposed bacteriocins such as enterocin DD14 (EntDD14) as potential therapeutic agents. However, the mechanism of macromolecular interaction of EntDD14 for the inhibition of SARS-CoV-2 is not yet fully understood, and its efficacy against variants like JN.1 has not been completely established. To address these knowledge gaps, biocomputational analyses were employed using a diverse set of tools, including Markov state models and volumetric analyses. This analysis revealed a favorable interaction between EntDD14 and the receptor-binding domain (RBD) of SARS-CoV-2. Furthermore, it was found that EntDD14 induces changes in the flexibility of the RBD and alters the distribution and size of its internal cavities, particularly in the JN.1 variant. These findings align with experimental observations and support the inhibitory mechanism of EntDD14 against SARS-CoV-2. Additionally, they suggest that EntDD14 may possess a broader spectrum of action, encompassing the JN.1 variant. This study paves the way for future investigations and therapeutic applications, encouraging further exploration of the antiviral activity of bacteriocins like EntDD14 against variants of concern like JN.1. However, additional experimental demonstrations are warranted to substantiate these findings.</div></div>","PeriodicalId":8979,"journal":{"name":"Biophysical chemistry","volume":"318 ","pages":"Article 107388"},"PeriodicalIF":3.3,"publicationDate":"2024-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143132616","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}

引用次数: 0