IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-07-24 DOI: 10.1002/cbic.202500401

Julie Maibøll Buhl, Sujata Mahapatra, Magnus Kjærgaard, Frans A A Mulder

{"title":"Quantification of Small Molecule Partitioning in a Biomolecular Condensate with 2D Nuclear Magnetic Resonance Spectroscopy.","authors":"Julie Maibøll Buhl, Sujata Mahapatra, Magnus Kjærgaard, Frans A A Mulder","doi":"10.1002/cbic.202500401","DOIUrl":"https://doi.org/10.1002/cbic.202500401","url":null,"abstract":"Several intrinsically disordered proteins have been shown to undergo phase separation into a dense and dilute phase and this process is intimately linked with the regulation of cellular processes. It is therefore highly relevant to know how metabolites partition between these phases. It is shown here that the partitioning of components in a complex mixture can be robustly obtained from a single set of 2D nuclear magnetic resonance (NMR) spectra recorded on the dilute and dense phases separately using \"time-zero extrapolated\" heteronuclear single quantum coherence (HSQC0) spectroscopy. The spectral separation power of 2D NMR spectroscopy circumvents the need for physical isolation or workup of the mixture components in the two samples. Using quantitative 1D 1H NMR, it is validated that the HSQC0 approach effectively removes all the undermining effects that plague quantification in common 2D NMR experiments, including differential attenuation due to relaxation in the two phases, pulse imperfections, partial decoupling, off-resonance effects, and incomplete coherence transfer in case of scalar coupling variation. These results should be of widespread interest as partitioning into biomolecular condensates is crucial for the calibration of computational physicochemical models of phase separation and key to the further understanding of cellular biochemistry involving membrane-less organelles.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2500401"},"PeriodicalIF":2.6,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Stereoselective Synthesis of Cannabidiol and its Unnatural Enantiomer to Evaluate Anxiolytic-Like Properties and Memory Interactions. 立体选择性合成大麻二酚及其非天然对映体以评估抗焦虑类性质和记忆相互作用。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-07-24 DOI: 10.1002/cbic.202500438

Marcos Accioly, Kawana Rosa, Andressa G Soliani, Suzete M Cerutti, Cristiano Raminelli

引用次数: 0

Dominant-Negative Effects of p53 R337 Variants in Li-Fraumeni Syndrome: Impact on Tetramer Formation and Transcriptional Activity. Li-Fraumeni综合征中p53 R337变异的显性负作用：对四聚体形成和转录活性的影响

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-07-24 DOI: 10.1002/cbic.202500330

Rui Kamada, Shuya Sakaguchi, Madoka Kanno, Takaaki Ozawa, Natsumi Nakagawa, James G Omichinski, Kazuyasu Sakaguchi

{"title":"Dominant-Negative Effects of p53 R337 Variants in Li-Fraumeni Syndrome: Impact on Tetramer Formation and Transcriptional Activity.","authors":"Rui Kamada, Shuya Sakaguchi, Madoka Kanno, Takaaki Ozawa, Natsumi Nakagawa, James G Omichinski, Kazuyasu Sakaguchi","doi":"10.1002/cbic.202500330","DOIUrl":"https://doi.org/10.1002/cbic.202500330","url":null,"abstract":"Li-Fraumeni syndrome (LFS) is an inherited cancer predisposition disorder caused by heterozygous TP53 mutations. Among these, missense mutations at Arg337-such as R337C and R337H-are common in LFS patients. Although many studies have characterized individual p53 variants in LFS, the impact of tetramerization domain (TD) mutations on wild-type (WT) p53 function remains unclear. Herein, a novel FRET-based assay system that enables the simultaneous detection of heterotetramer formation and p53-dependent transcriptional activity in live cells is developed. These results show that the heteromultimerization of the R337C variant with WT p53 is only slightly reduced compared to WT homotetramers, yet its transcriptional activity is diminished by over 50%. In contrast, the R337H variant forms heterotetramers at near-normal levels but exhibits markedly compromised transcriptional activity. These findings reveal a previously unrecognized dominant-negative-like effect, suggesting reduced p53 function is due not only to decreased tetramer formation but also to diminished heterotetramer stability. Moreover, the LFS-associated p53TD variants show a greater loss of activity against the low-affinity, apoptosis-inducing bax response element than against the high-affinity, cell cycle arrest-related CDKN1A response element. Collectively, this study demonstrates that p53TD mutations can exert dominant-negative effects, advancing the understanding of p53 heteromultimer function in LFS pathogenesis. These mechanistic insights into p53 heterotetramer stability may not only inform genetic screening strategies for LFS but also support future therapeutic approaches aimed at restoring p53 function by stabilizing mutant tetramers.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2500330"},"PeriodicalIF":2.6,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Activity Analysis of the P2X Receptor Antagonist PPADS against Signal Transducer and Activator of Transcription Proteins. P2X受体拮抗剂PPADS对转录蛋白信号转导和激活因子的活性分析。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-07-24 DOI: 10.1002/cbic.202500454

Angela Berg, Martin Gräber, Thorsten Berg

引用次数: 0

Hybridization Probes Featuring a Pyrenylpyridine C-Nucleoside or Its Palladacycle as a Fluorescent Sensor Moiety. 以Pyrenylpyridine c -核苷或其Palladacycle为荧光传感器片段的杂交探针。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-07-21 DOI: 10.1002/cbic.202500474

Dattatraya Uttam Ukale, Tuomas Lönnberg

{"title":"Hybridization Probes Featuring a Pyrenylpyridine C-Nucleoside or Its Palladacycle as a Fluorescent Sensor Moiety.","authors":"Dattatraya Uttam Ukale, Tuomas Lönnberg","doi":"10.1002/cbic.202500474","DOIUrl":"https://doi.org/10.1002/cbic.202500474","url":null,"abstract":"A C-nucleoside analog having pyren-1-ylpyridine as the base moiety has been synthesized and incorporated in the middle of a short oligodeoxynucleotide. A portion of this oligonucleotide is cyclopalladated at the modified residue, and the potential of both the metal-free and the palladacyclic oligonucleotide as hybridization probes for single-nucleotide polymorphism genotyping is assessed by melting studies on relevant duplexes using various techniques. Conventional ultraviolet (UV) melting profiles at 260 nm reveal considerable destabilization of the palladacyclic duplexes relative to their metal-free counterparts. Circular dichroism melting temperatures are higher than their UV counterparts, especially with the palladacyclic duplexes. Cyclopalladation markedly reduces the fluorescence emission of the pyrenylpyridine moiety, but both the metal-free and the palladacyclic oligonucleotide exhibit a qualitatively similar pattern of increased fluorescence on hybridization with a complementary sequence, consistent with the pyrene ring being \"pushed out\" of the base stack. Emission at low temperature is dependent on the nucleobase paired with the pyrenylpyridine base surrogate with both of the modified oligonucleotides. This discrimination is stronger with the palladacyclic oligonucleotide, possibly owing to Pd(II)-mediated base pairing.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2500474"},"PeriodicalIF":2.6,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144673420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Gold Nanoparticles Guided by Self-Assembling Peptides: From Sequence to Superstructure. 自组装肽引导的金纳米颗粒：从序列到上层结构。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-07-21 DOI: 10.1002/cbic.202500351

Simone Adorinni, Silvia Marchesan

引用次数: 0

Front Cover: Exploiting SpyTag/SpyCatcher Technology to Design New Artificial Catalytic Copper Proteins (ChemBioChem 14/2025) 封面：利用SpyTag/SpyCatcher技术设计新型人工催化铜蛋白（ChemBioChem 14/2025）

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-07-21 DOI: 10.1002/cbic.202581401

Silvia Gentili, Francesca Miglioli, Valentina Borghesani, Gloria Spagnoli, Denise Bellotti, Davide Cavazzini, Remo Guerrini, Maurizio Remelli, Giovanni Maestri, Simone Ottonello, Angelo Bolchi, Matteo Tegoni

引用次数: 0

A Browser-Based Tool for Assessing Accuracy of Isothermal Titration Calorimetry-Derived Parameters: K_d, ΔH°, and n. 一个基于浏览器的工具，用于评估等温滴定量热衍生参数的准确性：Kd， ΔH°和n。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-07-14 DOI: 10.1002/cbic.202500194

Tong Ye Wang, Amit Bijlani, Emily Hoi Pui Chao, Philip E Johnson, Sergey N Krylov

{"title":"A Browser-Based Tool for Assessing Accuracy of Isothermal Titration Calorimetry-Derived Parameters: Kd, ΔH°, and n.","authors":"Tong Ye Wang, Amit Bijlani, Emily Hoi Pui Chao, Philip E Johnson, Sergey N Krylov","doi":"10.1002/cbic.202500194","DOIUrl":"https://doi.org/10.1002/cbic.202500194","url":null,"abstract":"Accurate determination of equilibrium dissociation constants (Kd) is essential for decision-making in drug discovery and diagnostics development. Isothermal titration calorimetry (ITC), which requires no reactant labeling or immobilization, is commonly used to validate Kd values from high-throughput screens. Yet, like other methods, ITC results can be skewed by systematic errors in reactant concentrations, a fact that is often overlooked, potentially leading to misinformed decisions. To address this, accuracy confidence intervals (ACI)-ITC is developed, a browser-based tool that calculates ACI for ITC-derived parameters, offering probabilistic ranges for the true values of Kd, enthalpy change (ΔH°), and binding stoichiometry (n). Unlike traditional confidence intervals that consider only random errors, ACI-ITC explicitly accounts for systematic errors, providing a more accurate framework to assess experimental reliability. Alongside a user-friendly interface, it offers detailed guidance for determining uncertainties in concentrations and heat, which are critical inputs for assessing measurement accuracy. The tool's browser-based accessibility (https://aci.sci.yorku.ca) eliminates the need for specialized installation, enabling cross-platform compatibility and streamlining accuracy assessments. By highlighting the importance of systematic errors and providing a structured approach for their evaluation, ACI-ITC supports more robust conclusions, fosters better-informed decisions based on ITC measurements, and enhances the reliability of research findings.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2500194"},"PeriodicalIF":2.6,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Isomerized and Racemized Aspartyl and Deamidated Asparagine Residues Identified in ɣS-Crystallin. 异异构化和消旋化天冬氨酸和脱酰胺化天冬氨酸残基的鉴定。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-07-14 DOI: 10.1002/cbic.202500352

Victoria S Halls, Larry L David, Keith D Zientek, Kirsten J Lampi

{"title":"Isomerized and Racemized Aspartyl and Deamidated Asparagine Residues Identified in ɣS-Crystallin.","authors":"Victoria S Halls, Larry L David, Keith D Zientek, Kirsten J Lampi","doi":"10.1002/cbic.202500352","DOIUrl":"https://doi.org/10.1002/cbic.202500352","url":null,"abstract":"ɣS-crystallin is a major protein of the human lens and is highly modified with age and cataract due to a lack of lens protein turnover. Previous studies identify some sites of isomerization and racemization of deamidated asparaginyl and aspartyl residues in ɣS but have been limited due to the complexity of isoforms and difficulty in characterizing deamidation posttranslational modifications. A total of 32 stable isotope-labeled peptides are created for ɣS residues 7-18, 72-78, and 131-145, containing L-Asp, D-Asp, L-isoAsp, and D-isoAsp at D12, N14, N76, D77, and N143 to act as internal chromatography standards spiked into tryptic digests of nuclear insoluble protein of a cataractous human lens. High-resolution mass spectrometry is used to accurately assign deamidation status using the 19 mDa mass defect between isotopic peaks of deamidated and nondeamidated peptides. While peptides containing D-forms of Asp and isoAsp were assigned, the predominant isoforms contained L-isoAsp. High-resolution mass spectrometry using wide single ion monitoring data-independent acquisition also greatly improved the reliable identification of peptide deamidation states. These results will aid creation of ɣS using native chemical ligation to examine the role of isoAsp in crystallin aggregation and cataract.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2500352"},"PeriodicalIF":2.6,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Front Cover: Hybrid Molecules of Small Molecular and Peptidic HIV Fusion Inhibitors (ChemBioChem 13/2025) 封面：小分子和多肽HIV融合抑制剂的杂交分子（ChemBioChem 13/2025）

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-07-11 DOI: 10.1002/cbic.202581301

Kohei Tsuji, Takuya Kobayakawa, Peter Bolah, Soshi Nishimura, Tsutomu Murakami, Hirokazu Tamamura

引用次数: 0

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