Article
Chemistry, Multidisciplinary
Viola C. D'mello, Gildas Goldsztejn, Venkateswara Rao Mundlapati, Valerie Brenner, Eric Gloaguen, Florence Charnay-Pouget, David J. Aitken, Michel Mons
Summary: This study investigates the folding characteristics of asparagine-containing dipeptides into Asx turns and analyzes the behavior of Asx turns in protein structures. It is found that Asx turns in Asn-Ala sequences primarily adopt type I conformation, while Asx turns in Asn-Gly sequences mainly adopt type II conformation, possibly due to hydration.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Palanisamy Deepa, Duraisamy Thirumeignanam
Summary: This study investigates the significance of binding affinity between halogen and non-halogen derivatives of beta-d-Xylopyranose with amino acids of ruminant-beta-glycosidase. Through density functional theory analysis, it is shown that these derivatives exhibit strong interaction, providing clues for scientists to model new drugs.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Multidisciplinary Sciences
Eunhee Koh, Uijin Kim, Hyun-Soo Cho
Summary: Pathogenic bacteria encode virulent glycosyltransferases that conjugate various glycans onto host crucial proteins. This study focuses on the deficiency of E. coli NleB2 and S. enterica SseK2 effectors in glycosylation. The unique conformation of the DxD motif and triple Met-aromatic interactions may contribute to this deficiency.
SCIENTIFIC REPORTS
(2022)
Article
Chemistry, Physical
Qingqing Zhang, Yang Liu, Xueli Jia, Yuanyuan He, Ruigang Zhang, Tiantian Guan, Qi Zhang, Yonggang Yang, Yufang Liu
Summary: The photophysical and photochemical properties of a novel sensor and its reaction product with hydrogen sulfide were theoretically investigated, revealing strengthened hydrogen bonds in the excited state that facilitate intramolecular proton transfer and influence fluorescence properties, leading to changes in the measured spectra. The study provides insights into the detection mechanism for hydrogen sulfide using the fluorescent probe and serves as a reference for further probe studies.
JOURNAL OF MOLECULAR LIQUIDS
(2021)
Article
Chemistry, Multidisciplinary
Xingyue Li, Andrew L. Sabol, Patrick J. Salveson, James S. Nowick
Summary: Researchers have developed a new beta-turn template, (delta)MeOrn, which can induce a beta-hairpin conformation in peptides. This template demonstrates superior folding compared to (delta)Orn and is comparable to d-Pro-Gly.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Saqi Zhang, Qiang Li, Quntao Xie, Haowei Zhu, Weiwei Xu, Zhaozeng Liu
Summary: This paper used molecular dynamics simulation to study the viscosity reduction effects of ultrasound and viscosity reducers on heavy oil and their mechanism of interaction. The results showed that ultrasound and viscosity reducers had different effects on the viscosity reduction rate, hydrogen bond number, hydrogen bond type, and occupation rate. The type and content of viscosity reducer also affected the effect of ultrasonic viscosity reduction. In addition, the amplitude, frequency, and temperature of ultrasound were also factors affecting the viscosity reducers' effect.
Article
Chemistry, Organic
Richard C. Knighton, Paul D. Beer
Summary: A novel method was used to construct a mechanically interlocked ion-pair binding [2]catenane, with the heteroditopic binding mode elucidated by single-crystal X-ray crystallography, revealing an unprecedented 'macrocycle separated' ion-pair configuration with alkali-metal sodium cation.
ORGANIC CHEMISTRY FRONTIERS
(2021)
Article
Chemistry, Multidisciplinary
Lorenzo Sori, Andrea Pizzi, Nicola Demitri, Giancarlo Terraneo, Antonio Frontera, Pierangelo Metrangolo
Summary: This study investigates the crystal structures and density functional theory of two bis-halogenated tyrosines, revealing the subtle relationship between hydrogen and halogen bonds in promoting supramolecular self-assembly.
Article
Chemistry, Multidisciplinary
Yutang Li, Daniel Strand, Stefan Grimme, Stefan Jonsson, Kenneth Warnmark
Summary: The challenging synthesis of a fused C-3-symmetric trilactam was accomplished in both racemic and enantiomerically pure forms. The study of its self-assembly revealed different hydrogen bond patterns in crystals of rac-1-d(3) and (+)-(SSS)-1.
CHEMICAL COMMUNICATIONS
(2022)
Review
Chemistry, Inorganic & Nuclear
Suvendu Paul, Tapas Majumdar, Arabinda Mallick
Summary: This review focuses on the optical recognition of hydrogen sulfate based on hydrogen bonding over the past two decades, discussing mechanisms such as hydrogen-bond-driven proton transfer, ESIPT, ICT, PET, CHEF, and TBET. Key points of the sensing process, spectroscopic changes, selectivity, sensitivity, naked-eye color changes, reusability of sensors, and in vivo detection of HSO4- are emphasized, with special attention to the correlation between photophysical changes and recognition mechanisms.
DALTON TRANSACTIONS
(2021)
Article
Chemistry, Applied
Miao Hu, Qiang Yue, Guannan Liu, Yijia Jia, Yang Li, Baokun Qi
Summary: This study investigated the complexation mechanism, structure, and functional properties of the complexes of 7S/11S with SA blocks. The results showed that the complexes exhibited good emulsifying properties and thermal stability.
Article
Chemistry, Organic
Ji-Ming Xi, Yun-Hai Sun, Wen-Cheng Li, Yu-Heng Wu, Zhong-Lin Wei, Wei-Wei Liao
Summary: A copper-catalyzed alkene-trifluoromethylation-triggered nitrile insertion/remote functionalization relay process has been developed, which involves the generation of iminyl radical intermediates through interrupted remote 1,n-difunctionalizations of alkenes with nitrite insertion, followed by subsequent 1,n-HAT to achieve remote functionalization. This relay protocol provides a straightforward approach for the assembly of structurally diverse trifluoromethylated azaheterocycles.
Article
Biochemistry & Molecular Biology
Honey Jain, Konstantina Karathanou, Ana-Nicoleta Bondar
Summary: Phosphatidylserine lipids, anionic molecules found in eukaryotic plasma membranes, play essential roles in cellular physiology. Understanding the altered distribution of phosphatidylserine, particularly in apoptotic cancer cells, has important implications for biomarker development. This study utilizes a graph algorithm to study the dynamics of water-mediated lipid clusters at the interface of a model bilayer, providing insights into the behavior of phosphatidylserine in the presence of cholesterol.
Article
Biochemistry & Molecular Biology
M. Trent Kemp, Derek A. Nichols, Xiujun Zhang, Kyle Defrees, Insung Na, Adam R. Renslo, Yu Chen
Summary: The study characterized the function of the Asp233-Asp246 pair in Class A beta-lactamases using CTX-M-14 beta-lactamase. The D233N mutation led to decreased activity depending on the substrate, while also reducing the binding of a reversible inhibitor. Structural analysis revealed changes in loop movement and hydrogen bond loss, highlighting the importance of the aspartate pair in substrate hydrolysis and suggesting increased protein flexibility as a means to evolve drug resistance.
Article
Biochemistry & Molecular Biology
Jose Manuel Guevara-Vela, Miguel Gallegos, Monica A. Valentin-Rodriguez, Aurora Costales, Tomas Rocha-Rinza, Angel Martin Pendas
Summary: This article evaluates the strength of RAHB by investigating the impact of substituents and the relationship between formation energy and hydrogen bond interaction energy. The study shows that substituents' effects on RAHB depend on their position within the molecular structure, casting doubts on the use of different parameters as indicators.
Article
Biochemistry & Molecular Biology
Shuntaro Chiba, Kenji Rowel Q. Lim, Narin Sheri, Saeed Anwar, Esra Erkut, Md Nur Ahad Shah, Tejal Aslesh, Stanley Woo, Omar Sheikh, Rika Maruyama, Hiroaki Takano, Katsuhiko Kunitake, William Duddy, Yasushi Okuno, Yoshitsugu Aoki, Toshifumi Yokota
Summary: Exon skipping using ASOs is a powerful tool for mRNA splicing modulation, but selecting the optimal sequence is difficult. We developed a computational method to design effective ASOs for exon skipping, incorporating machine learning algorithms and experimental data. eSkip-Finder is a web-based resource with a predictor for exon skipping efficacy of ASOs and a database of ASOs.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Multidisciplinary Sciences
Vasileios L. Zogopoulos, Georgia Saxami, Apostolos Malatras, Antonia Angelopoulou, Chih-Hung Jen, William J. Duddy, Gerasimos Daras, Polydefkis Hatzopoulos, David R. Westhead, Ioannis Michalopoulos
Summary: Gene coexpression analysis aims to identify sets of genes with similar expression patterns across multiple data sets, such as microarray experiments. The Arabidopsis Coexpression Tool (ACT) generates a coexpression tree from processed microarray data, revealing relationships between different genes. ACT offers a user-friendly interface for gene set enrichment analysis and is successful in identifying both ubiquitous and tissue-specific gene expressions.
Article
Clinical Neurology
Gavin McCluskey, William Duddy, Stephen Haffey, Karen Morrison, Colette Donaghy, Stephanie Duguez
Summary: The study evaluated the incidence, prevalence, and survival trends of motor neurone disease (MND) in Northern Ireland from 2015 to 2019. The incidence and prevalence rates of MND have increased over the past 10 years, in line with trends in other European countries. Improved survival was associated with younger age at onset, longer time to diagnosis, attendance at a regional MND clinic, and outpatient presentation to a Neurology Department.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Article
Chemistry, Medicinal
Gabriele Fumagalli, Rodrigo J. Carbajo, J. Willem M. Nissink, Jonathan Tart, Rongxuan Dou, Andrew P. Thomas, David R. Spring
Summary: The study focused on the identification of pan-mutant RAS inhibitors by designing novel peptides using a binding pharmacophore. Through a chemically divergent approach, the researchers generated a library of small stapled peptides and optimized them to create low-micromolar binders of KRAS that inhibit nucleotide exchange.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Cell Biology
Ekene Anakor, Laura Le Gall, Julie Dumonceaux, William John Duddy, Stephanie Duguez
Summary: Intercellular communication between neurons and their surrounding cells occurs through secretion of soluble molecules or release of vesicles like exosomes, which play a role in maintaining brain homeostasis. Exosomes are suspected to spread toxic proteins in neurodegenerative conditions associated with aging. This review focuses on the role of exosomes in aging and specifically in ALS, highlighting their potential use as biomarkers and therapeutics for the disease.
Article
Geriatrics & Gerontology
Laura Le Gall, William J. Duddy, Cecile Martinat, Virginie Mariot, Owen Connolly, Vanessa Milla, Ekene Anakor, Zamalou G. Ouandaogo, Stephanie Millecamps, Jeanne Laine, Udaya Geetha Vijayakumar, Susan Knoblach, Cedric Raoul, Olivier Lucas, Jean Philippe Loeffler, Peter Bede, Anthony Behin, Helene Blasco, Gaelle Bruneteau, Maria Del Mar Amador, David Devos, Alexandre Henriques, Adele Hesters, Lucette Lacomblez, Pascal Laforet, Timothee Langlet, Pascal Leblanc, Nadine Le Forestier, Thierry Maisonobe, Vincent Meininger, Laura Robelin, Francois Salachas, Tanya Stojkovic, Giorgia Querin, Julie Dumonceaux, Gillian Butler Browne, Jose-Luis Gonzalez De Aguilar, Stephanie Duguez, Pierre Francois Pradat
Summary: Muscle vesicles may be a potential source of vesicle-mediated toxicity in ALS, as they are shown to be toxic to MNs.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2022)
Article
Cell Biology
Ekene Anakor, Vanessa Milla, Owen Connolly, Cecile Martinat, Pierre Francois Pradat, Julie Dumonceaux, William Duddy, Stephanie Duguez
Summary: Extracellular vesicles play a crucial role in intercellular communication and their study in Amyotrophic Lateral Sclerosis (ALS) is important. The smaller exosome-like vesicles from ALS patients have negative effects on motor neurons, astrocytes, and myotubes, while vesicles from healthy subjects or larger vesicles from ALS or healthy subjects do not exhibit such effects.
Review
Health Care Sciences & Services
Gavin McCluskey, Colette Donaghy, Karen E. Morrison, John McConville, William Duddy, Stephanie Duguez
Summary: Amyotrophic Lateral Sclerosis (ALS), Spinal Bulbar Muscular Atrophy (SBMA), and Spinal Muscular Atrophy (SMA) are motor neuron diseases characterized by progressive motor neuron degeneration, weakness, and muscular atrophy. Lipid dysregulation, particularly in sphingolipid metabolism, plays a significant role in the pathophysiology of these diseases. Several studies have shown that sphingomyelin (SM) and ceramide levels are elevated in ALS patients and correlated with clinical progression, suggesting their potential as biomarkers. Potential therapeutic strategies targeting sphingolipid metabolism are also discussed.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Chemistry, Medicinal
James S. Scott, Darren Stead, Bernard Barlaam, Jason Breed, Rodrigo J. Carbajo, Elisabetta Chiarparin, Natalie Cureton, Paul R. J. Davey, David I. Fisher, Eric T. Gangl, Tyler Grebe, Ryan D. Greenwood, Sudhir Hande, Holia Hatoum-Mokdad, Samantha J. Hughes, Thomas A. Hunt, Tony Johnson, Stefan L. Kavanagh, Teresa C. M. Klinowska, Carrie J. B. Larner, Mandy Lawson, Andrew S. Lister, David Longmire, Stacey Marden, Thomas M. McGuire, Caroline McMillan, Lindsay McMurray, Christopher J. Morrow, J. Willem M. Nissink, Thomas A. Moss, Daniel H. O'Donovan, Radoslaw Polanski, Stephen Stokes, Kumar Thakur, Dawn Trueman, Caroline Truman, Michael J. Tucker, Haixia Wang, Nicky Whalley, Dedong Wu, Ye Wu, Bin Yang, Wenzhan Yang
Summary: In this study, we optimized a series of selective estrogen receptor degrader (SERD) antagonists for the treatment of ER+ breast cancer. Through structure-based design and the use of modeling and NMR, we obtained a highly potent series of basic SERDs with promising physicochemical properties. By forming a zwitterion, we successfully eliminated hERG activity and identified compound 38 as a highly potent SERD capable of effectively degrading ER alpha.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Cell Biology
Vasileios L. Zogopoulos, Apostolos Malatras, Konstantinos Kyriakidis, Chrysanthi Charalampous, Evanthia A. Makrygianni, Stephanie Duguez, Marianna A. Koutsi, Marialena Pouliou, Christos Vasileiou, William J. Duddy, Marios Agelopoulos, George P. Chrousos, Vassiliki A. Iconomidou, Ioannis Michalopoulos
Summary: HGCA2.0 is a webtool that studies the global coexpression of human genes. It analyzes a large-scale dataset of healthy individuals' RNA samples and presents coexpressed subclades to the gene of interest, providing various enrichments analysis on gene ontologies, biological pathways, protein families, and diseases, as well as revealing enriched transcription factors. It has been successful in identifying genes with ubiquitous and tissue-specific expression patterns.
Review
Health Care Sciences & Services
Ekene Anakor, William John Duddy, Stephanie Duguez
Summary: Amyotrophic lateral sclerosis is a disease that affects the upper and lower motor neurons. It has been found that the disease not only affects motor neurons, but also other tissues and cell types, leading to metabolic dysfunctions, impaired proteostasis, deficits in muscle regeneration and RNA metabolism. Skeletal muscle is considered an important contributor to the occurrence and progression of the disease, acting as a secretory organ and affecting the skeletal muscle secretome, which can have consequences for neuronal function and survival.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Review
Health Care Sciences & Services
Christina Vasilopoulou, Stephanie Duguez, William Duddy
Summary: This review collects gene-set analysis studies related to ALS, using GWAS or individual-based genotype data, exploring their methodology and ALS-associated molecular pathways. By summarizing the limitations of standard single-gene analyses and highlighting the advantages of gene-set analysis, an overview of the statistical properties of gene-set analysis and related concepts is provided. The main aims of this review are to investigate the reproducibility of the collected studies and identify their strengths and limitations, in order to enhance the experimental design and quality of future studies, deepening our understanding of this disease.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Review
Biology
Gavin McCluskey, Karen E. Morrison, Colette Donaghy, Frederique Rene, William Duddy, Stephanie Duguez
Summary: Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease with complex pathogenesis involving disruption of multiple pathways. Extracellular vesicles (EVs), nanoscopic membrane-bound particles, play a crucial role in intercellular communication, and their involvement in ALS pathogenesis is increasingly recognized.
Article
Biochemistry & Molecular Biology
Christina Vasilopoulou, Sarah L. L. McDaid-McCloskey, Gavin McCluskey, Stephanie Duguez, Andrew P. P. Morris, William Duddy
Summary: This study aimed to identify and explore biological pathways and other gene sets associated with ALS using genomic data from the dbGaP repository. A large ALS-control cohort of European descent was assembled, and gene-set analysis revealed statistically significant associations with gene sets related to immune response, apoptosis, lipid metabolism, neuron differentiation, muscle cell function, synaptic plasticity, and development. Novel interactions between gene sets were also observed, suggesting mechanistic overlaps.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Medicinal
Joao Morado, Paul N. Mortenson, J. Willem M. Nissink, Jonathan W. Essex, Chris-Kriton Skylaris
Summary: We present a comparative study on the performance of different molecular models in simulating the stability and properties of 10 gamma-fluorohydrins. The results show that the ANI-2x model tends to predict stronger hydrogen bonding and overstabilize global minima, while conventional force fields still play an important role in condensed-phase simulations. This study provides guidelines for the future development and application of force fields and machine learning potentials.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)