Communications Chemistry最新文献

Pathway regulation mechanism by cotranslational protein folding. 共翻译蛋白折叠的通路调控机制。

IF 6.2 2区化学

Communications Chemistry Pub Date : 2025-08-01 DOI: 10.1038/s42004-025-01636-6

Peng Tao, Yi Xiao

{"title":"Pathway regulation mechanism by cotranslational protein folding.","authors":"Peng Tao, Yi Xiao","doi":"10.1038/s42004-025-01636-6","DOIUrl":"https://doi.org/10.1038/s42004-025-01636-6","url":null,"abstract":"Existing experimental results indicate potential disparities between cotranslational protein folding in vivo and free folding in vitro, yet the microscopic mechanisms responsible for these differences remain elusive. In this study, we devised a general protein cotranslational folding (GPCTF) simulations framework by modeling the ribosomal exit tunnel and translation process. Utilizing the GPCTF framework, we conducted extensive molecular dynamics simulations on three proteins of varying topologies, generating over 8 milliseconds of total trajectories. When compared to free folding, cotranslational folding enables the nascent peptide to adopt a more helix-rich structure with less nonnative interactions upon expulsion from the ribosomal exit tunnel. Notably, subsequent folding of this structure adheres to the same pathway as free folding, but with different ratios of folding pathways, modulated by the translation speed. This investigation illuminates the pathway regulation mechanism inherent to cotranslational folding and successfully reconciles discrepancies in pre-existing experimental results, offering significant insights into the protein folding process in vivo.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":"8 1","pages":"226"},"PeriodicalIF":6.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A bottom-up approach to find lead compounds in expansive chemical spaces. 一种在广阔的化学空间中寻找铅化合物的自下而上的方法。

IF 6.2 2区化学

Communications Chemistry Pub Date : 2025-08-01 DOI: 10.1038/s42004-025-01610-2

Álvaro Serrano-Morrás, Andrea Bertran-Mostazo, Marina Miñarro-Lleonar, Arnau Comajuncosa-Creus, Adrià Cabello, Carme Labranya, Carmen Escudero, Tian V Tian, Inna Khutorianska, Dmytro S Radchenko, Yurii S Moroz, Lucas Defelipe, David Ruiz-Carrillo, Maria Garcia-Alai, Robert Schmidt, Matthias Rarey, Patrick Aloy, Carles Galdeano, Jordi Juárez-Jiménez, Xavier Barril

{"title":"A bottom-up approach to find lead compounds in expansive chemical spaces.","authors":"Álvaro Serrano-Morrás, Andrea Bertran-Mostazo, Marina Miñarro-Lleonar, Arnau Comajuncosa-Creus, Adrià Cabello, Carme Labranya, Carmen Escudero, Tian V Tian, Inna Khutorianska, Dmytro S Radchenko, Yurii S Moroz, Lucas Defelipe, David Ruiz-Carrillo, Maria Garcia-Alai, Robert Schmidt, Matthias Rarey, Patrick Aloy, Carles Galdeano, Jordi Juárez-Jiménez, Xavier Barril","doi":"10.1038/s42004-025-01610-2","DOIUrl":"https://doi.org/10.1038/s42004-025-01610-2","url":null,"abstract":"Drug discovery starts with the identification of a \"hit\" compound that, following a long and expensive optimization process, evolves into a drug candidate. Bigger screening collections increase the odds of finding more and better hits. For this reason, large pharmaceutical companies have invested heavily in high-throughput screening (HTS) collections that can contain several million compounds. However, this figure pales in comparison with the emergent on-demand chemical collections, which have recently reached the trillion scale. These chemical collections are potentially transformative for drug discovery, as they could deliver many diverse and high-quality hits, even reaching lead-like starting points. But first, it will be necessary to develop computational tools capable of efficiently navigating such massive virtual collections. To address this challenge, we have conceived an innovative strategy that explores the chemical universe from the bottom up, performing a systematic search on the fragment space (exploration phase), to then mine the most promising areas of on-demand collections (exploitation phase). Using a hierarchy of increasingly sophisticated computational methods to remove false positives, we maximize the success probability and minimize the overall computational cost. A basic implementation of the concept has enabled us to validate the strategy prospectively, allowing the identification of new BRD4 (BD1) binders with potencies comparable to stablished drug candidates.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":"8 1","pages":"225"},"PeriodicalIF":6.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Reference library for suspect screening of environmental toxicants using ion mobility spectrometry-mass spectrometry. 使用离子迁移谱-质谱法筛选环境毒物的参考文库。

IF 6.2 2区化学

Communications Chemistry Pub Date : 2025-08-01 DOI: 10.1038/s42004-025-01619-7

Devin Teri, Noor A Aly, James N Dodds, Jian Zhang, Paul A Thiessen, Evan E Bolton, Kara M Joseph, Antony J Williams, Emma L Schymanski, Ivan Rusyn, Erin S Baker

{"title":"Reference library for suspect screening of environmental toxicants using ion mobility spectrometry-mass spectrometry.","authors":"Devin Teri, Noor A Aly, James N Dodds, Jian Zhang, Paul A Thiessen, Evan E Bolton, Kara M Joseph, Antony J Williams, Emma L Schymanski, Ivan Rusyn, Erin S Baker","doi":"10.1038/s42004-025-01619-7","DOIUrl":"https://doi.org/10.1038/s42004-025-01619-7","url":null,"abstract":"Due to the potential health risks related to chemical exposure, rapidly assessing xenobiotic molecules in the environment and those already in the body is imperative. Targeted analytical methods coupling either gas or liquid chromatography with mass spectrometry (GC-MS or LC-MS) are commonly utilized in current exposure assessments. While these methods are accepted as the gold standard for exposure analyses, they often require multiple sample preparation steps and analysis times > 30 min. These limitations have resulted in an evolving interest in using ion mobility spectrometry and MS (IMS-MS), either with or without chromatography, to improve throughput and annotation confidence. To increase IMS-MS information availability for exposure studies, here we utilized drift tube IMS-MS to evaluate 4685 xenobiotic chemical standards from the Environmental Protection Agency Toxicity Forecaster (ToxCast) programme, including pesticides, industrial chemicals, pharmaceuticals, consumer products, and per- and polyfluoroalkyl substances. Collision cross section (CCS) and m/z values were detected for 2144 unique chemicals with high confidence and reproducibility (≤1% error intra-laboratory and ≤2% inter-laboratory), resulting in values for 4004 [M + H]+, [M+Na]+, [M-H]- and [M]•+ ion types. This multidimensional database therefore supports suspect screening for a wider range of environmental contaminants, faster exposure response times, and assessments of xenobiotic-disease connections.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":"8 1","pages":"224"},"PeriodicalIF":6.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144764674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Photo-CIDNP for quantification of micromolar analytes in urine. photocidnp用于尿液中微量摩尔分析物的定量。

IF 6.2 2区化学

Communications Chemistry Pub Date : 2025-08-01 DOI: 10.1038/s42004-025-01626-8

Marta Stefańska, Thomas Müntener, Sebastian Hiller

{"title":"Photo-CIDNP for quantification of micromolar analytes in urine.","authors":"Marta Stefańska, Thomas Müntener, Sebastian Hiller","doi":"10.1038/s42004-025-01626-8","DOIUrl":"https://doi.org/10.1038/s42004-025-01626-8","url":null,"abstract":"Towards target diagnostics of low-concentrated molecules in biofluids, NMR spectroscopy faces limitations due to low sensitivity, signal overlap, and high equipment costs. Hyperpolarization methods such as photo-chemically induced dynamic nuclear polarization (photo-CIDNP) can mitigate some of these challenges. In this study, we explore the potential of steady-state photo-CIDNP to quantify target molecules in urine samples. Matrix interference poses a significant challenge to quantitative measurements, and we thus establish two counteracting methods: spiking and biofluid dilution. Experiments conducted in both high (14.1 T) and low (1.9 T) magnetic fields demonstrate the effectiveness of photo-CIDNP-based quantification at micromolar levels for the analytes sumatriptan and paracetamol. We report limits of quantification (LOQs) in complex matrices down to 3.5 μM and average errors of less than 26% with the spiking method and less than 11% using biofluid dilution. This proof-of-concept study highlights the potential of NMR supported by photo-CIDNP as a target diagnostic tool for rapid drug quantification and clinical monitoring applications, especially with low-cost benchtop NMR devices.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":"8 1","pages":"223"},"PeriodicalIF":6.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ultrafast probing of isotope-induced explicit symmetry breaking in ethylene. 乙烯中同位素诱导显对称破缺的超快探测。

IF 6.2 2区化学

Communications Chemistry Pub Date : 2025-07-31 DOI: 10.1038/s42004-025-01621-z

Alessandro Nicola Nardi, Alexie Boyer, Yaowei Hu, Vincent Loriot, Franck Lépine, Morgane Vacher, Saikat Nandi

{"title":"Ultrafast probing of isotope-induced explicit symmetry breaking in ethylene.","authors":"Alessandro Nicola Nardi, Alexie Boyer, Yaowei Hu, Vincent Loriot, Franck Lépine, Morgane Vacher, Saikat Nandi","doi":"10.1038/s42004-025-01621-z","DOIUrl":"https://doi.org/10.1038/s42004-025-01621-z","url":null,"abstract":"Symmetry governs nature's laws, yet many of the natural phenomena occur due to the breakdown of symmetry. Here, we show how isotope-induced inversion symmetry breaking influences ultrafast photoisomerization processes in ethylene. Using extreme ultraviolet pump - near infrared probe time-of-flight mass spectrometry, we find that replacing one of the carbon atoms in ethylene with a 13C isotope leads to twice-faster structural relaxation via ethylene-ethylidene isomerization in the photo-excited molecular cation. Advanced trajectory surface hopping calculations incorporating the nuclear symmetry of the molecular systems, reveal that it arises from the mixing of different normal modes in the isotope-substituted species, interactions otherwise forbidden by symmetry. Although the mixing does not alter the symmetry of the electronic Hamiltonian, it modifies that of the nuclear Hamiltonian, causing explicit symmetry breaking. This facilitates efficient intra-molecular vibrational energy redistribution, lowering the isomerization yield. Our findings offer opportunities to use isotope-induced nuclear symmetry breaking to control the outcome of light-molecule interactions across ultrafast timescales.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":"8 1","pages":"222"},"PeriodicalIF":6.2,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Titanocenes functionalization with high chemical diversity via titanium protecting groups. 通过钛保护基团实现高化学多样性的二茂钛基团功能化。

IF 6.2 2区化学

Communications Chemistry Pub Date : 2025-07-30 DOI: 10.1038/s42004-025-01624-w

Emanuele Casali, Andrea Gandini, Gabriele Merlo, Lorenzo Carli, Jan J Weigand, Alessio Porta, Giuseppe Zanoni

{"title":"Titanocenes functionalization with high chemical diversity via titanium protecting groups.","authors":"Emanuele Casali, Andrea Gandini, Gabriele Merlo, Lorenzo Carli, Jan J Weigand, Alessio Porta, Giuseppe Zanoni","doi":"10.1038/s42004-025-01624-w","DOIUrl":"10.1038/s42004-025-01624-w","url":null,"abstract":"Titanocenes are well-recognized for their diverse applications in catalysis and biomedical research. Despite their potential, challenges related to stability and functionalization have limited broader utility, especially in medicinal chemistry. In this study, we present a strategy for the functionalization of titanocenes using a class of titanium protecting groups. This approach provides enhanced control over reactivity and significantly broadens the scope of structurally diverse modifications accessible for these complexes. Furthermore, we demonstrate the successful integration of a BODIPY fluorophore into titanocene-based systems, enabling advanced cellular imaging and visualizing the real perinuclear distribution of these organometallic compounds in living cell. The efficient incorporation of biomolecules such as biotin and cholesteryl derivatives through click-chemistry ligation underscores the potential of this method to facilitate the development of titanocene-based agents for pharmaceutical applications. By addressing previous limitations, this work paves the way for more effective utilization of titanocenes in both synthetic and biomedical fields.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":"8 1","pages":"221"},"PeriodicalIF":6.2,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12310976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cardiolipin acyl chain composition tailors the conformation of mammalian ATP synthase dimers. 心磷脂酰基链的组成决定了哺乳动物ATP合酶二聚体的构象。

IF 6.2 2区化学

Communications Chemistry Pub Date : 2025-07-30 DOI: 10.1038/s42004-025-01611-1

M Makowski, V G Almendro-Vedia, I López-Montero

引用次数: 0

Synthesis, biological evaluation and clinical trials of Cereblon-based PROTACs. 小脑基PROTACs的合成、生物学评价及临床试验。

IF 6.2 2区化学

Communications Chemistry Pub Date : 2025-07-29 DOI: 10.1038/s42004-025-01598-9

André T S Vicente, Sara P S P Moura, Jorge A R Salvador

引用次数: 0

Structural molecular details of the endocytic adaptor protein CALM upon binding with phosphatidylinositol 4,5-bisphosphate-containing model membranes. 与含4,5-二磷酸磷脂酰肌醇模型膜结合的内吞衔接蛋白CALM的结构分子细节。

IF 6.2 2区化学

Communications Chemistry Pub Date : 2025-07-29 DOI: 10.1038/s42004-025-01590-3

Andreas Santamaria, Daniel Pereira, Nisha Pawar, Bernard T Kelly, Javier Carrascosa-Tejedor, Mariana Sardo, Luís Mafra, Giovanna Fragneto, David J Owen, Ildefonso Marín-Montesinos, Eduardo Guzmán, Nathan R Zaccai, Armando Maestro

{"title":"Structural molecular details of the endocytic adaptor protein CALM upon binding with phosphatidylinositol 4,5-bisphosphate-containing model membranes.","authors":"Andreas Santamaria, Daniel Pereira, Nisha Pawar, Bernard T Kelly, Javier Carrascosa-Tejedor, Mariana Sardo, Luís Mafra, Giovanna Fragneto, David J Owen, Ildefonso Marín-Montesinos, Eduardo Guzmán, Nathan R Zaccai, Armando Maestro","doi":"10.1038/s42004-025-01590-3","DOIUrl":"10.1038/s42004-025-01590-3","url":null,"abstract":"Clathrin assembly lymphoid myeloid leukaemia protein (CALM) is involved in the formation of clathrin-mediated endocytic coats by virtue of binding many proteins involved in the process, including clathrin itself and AP2 cargo adaptor complex. CALM is able to specifically recognize the inner leaflet of the plasma membrane by binding the membrane's phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). Here, a quantitative biophysical approach -combining neutron/X-ray scattering, solid-state NMR, atomic force microscopy, and quartz crystal microbalance with dissipation monitoring-, was exploited to investigate CALM interaction with PtdIns(4,5)P2-presenting model membranes. The presented experimental data reveal CALM's folded domain partially embeds (12% volume occupancy) within the membrane, directly coordinating a cluster of 4 to 5 PtdIns(4,5)P2 molecules via phosphate interactions. The N-terminal amphipathic helix inserts ~8 Å into the headgroup region, reducing local membrane stiffness by 36% (from 22 to 14 MPa) while increasing viscoelastic dissipation. These results establish a plausible threefold curvature-generation mechanism: PtdIns(4,5)P2 clustering, helix insertion-induced lipid compaction and global mechanical softening-collectively lowering the energy barrier for membrane deformation.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":"8 1","pages":"219"},"PeriodicalIF":6.2,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12307879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Publisher Correction: Locating hydrogen in the Mg₅Bi₃H_x Zintl phase. 更正：定位氢在Mg5Bi3Hx Zintl相。

IF 6.2 2区化学

Communications Chemistry Pub Date : 2025-07-28 DOI: 10.1038/s42004-025-01616-w

Teuta Neziraj, Lev Akselrud, Marcus Schmidt, Ulrich Burkhardt, Yuri Grin, Ulrich Schwarz

引用次数: 0