IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-06-11 DOI: 10.1002/cbic.202500289

Barak Akabayov, Adi Dayan, Stefan Ilic

引用次数: 0

Chemoenzymatic Synthesis of 3-Halochromones via Oxidative α-Halogenation of Enaminones in TPGS-750-M Micelles. TPGS-750-M胶束中胺酮氧化α-卤化合成3-卤代酮的化学酶法研究。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-06-11 DOI: 10.1002/cbic.202500277

Chisanu Krongyut, Jakkarin Limwongyut, Nittaya Wiriya, Anyanee Kamkaew, Ailada Jantasin, Rung-Yi Lai

{"title":"Chemoenzymatic Synthesis of 3-Halochromones via Oxidative α-Halogenation of Enaminones in TPGS-750-M Micelles.","authors":"Chisanu Krongyut, Jakkarin Limwongyut, Nittaya Wiriya, Anyanee Kamkaew, Ailada Jantasin, Rung-Yi Lai","doi":"10.1002/cbic.202500277","DOIUrl":"https://doi.org/10.1002/cbic.202500277","url":null,"abstract":"Synthesis strategies of chromones have been widely investigated due to the abundance of chromone moiety in bioactive compounds and natural products. Of which, 3-halochromones are a versatile set of precursors to synthetically access valuable compounds with chromone frameworks. Generally, 3-halochromones were synthesized from o-hydroxy enaminones through oxidative α-halogenation, a process that often uses toxic and corrosive chemicals. Herein, we present an alternative strategy of oxidative α-halogenation catalyzed by vanadium-dependent chloroperoxidase from Curvularia inaequalis (CiVCPO) with H2O2/KX (X = Cl, Br, and I) in an aqueous medium. With a micellar system from a surfactant TPGS-750-M, substrate concentration can be increased to 50 mM without compromising the yield, thereby significantly reducing the use of organic solvents. Substrate scope investigation revealed that bromination and chlorination processes prefer electron-donating substituents although moderate electron-withdrawing groups were tolerated (20 examples). Additionally, iodination processes can be performed under the optimized condition. However, slow conversion indicated that further optimization is needed. We also found that iodination can occur without CiVCPO, albeit at a lower conversion. Further investigation suggested that such a conversion took place via I2 generated in situ. Overall, this chemoenzymatic method could offer an environmentally friendly approach to access a variety of 3-bromo or 3-chlorochromones.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500277"},"PeriodicalIF":2.6,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264932","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

Rational Design and Bioactive Screening of Peptide Inhibitors Targeting Host-Pathogen Interactions in Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV). 针对发热伴血小板减少综合征病毒（SFTSV）宿主-病原体相互作用肽抑制剂的合理设计和生物活性筛选

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-06-10 DOI: 10.1002/cbic.202500296

Zhipeng Hu, Lixin Yang, Tingting Zhou, Dan Wang, Jie Xu, Naiwen Zhang, Dongbo Tang, Yifang Han, Hai Qian, Wei Shi

{"title":"Rational Design and Bioactive Screening of Peptide Inhibitors Targeting Host-Pathogen Interactions in Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV).","authors":"Zhipeng Hu, Lixin Yang, Tingting Zhou, Dan Wang, Jie Xu, Naiwen Zhang, Dongbo Tang, Yifang Han, Hai Qian, Wei Shi","doi":"10.1002/cbic.202500296","DOIUrl":"https://doi.org/10.1002/cbic.202500296","url":null,"abstract":"Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) poses a significant threat to public health, with limited therapeutic options available. This study focuses on the rational design and screening of peptide inhibitors targeting host-pathogen interactions, specifically between the viral Gn glycoprotein and key host cell receptors, DC-SIGN and NMMHC-IIA. By employing molecular dynamics simulations, alanine scanning, and peptide docking techniques, peptides were designed to disrupt these protein-protein interactions. Among the synthesized candidates, peptides II-1 and II-4 demonstrated potent inhibitory activity against SFTSV infection, with reduced TCID50 values in cellular assays and displayed exceptional affinity (KD = 7.381 × 10-8 M, 1.439 × 10-8 M), These peptides also exhibited low cytotoxicity and hemolytic toxicity, highlighting their safety profile. Molecular dynamics simulations confirmed strong binding affinities for these peptides, underpinned by stable hydrogen bonding interactions. This research provides a promising platform for developing peptide-based therapeutics targeting SFTSV, paving the way for further preclinical evaluation and clinical applications.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500296"},"PeriodicalIF":2.6,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144256901","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

α-Synuclein Sequences from Long-Lived Animals Display Generally Diminished Aggregation Compared to Shorter-Lived Animals Including Humans. 与包括人类在内的寿命较短的动物相比，长寿动物α-突触核蛋白序列的聚集性普遍降低。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-06-10 DOI: 10.1002/cbic.202500340

Gilbert B Ampomah, Eldon R Hard, Matthew Robert Pratt

{"title":"α-Synuclein Sequences from Long-Lived Animals Display Generally Diminished Aggregation Compared to Shorter-Lived Animals Including Humans.","authors":"Gilbert B Ampomah, Eldon R Hard, Matthew Robert Pratt","doi":"10.1002/cbic.202500340","DOIUrl":"https://doi.org/10.1002/cbic.202500340","url":null,"abstract":"The overall process of protein aggregation from soluble species to amyloid fibrils is toxic to neurons and can propagate along neuronal connections in ways that potentially explain the pathological progression in most neurodegenerative diseases. One of these aggregation-prone proteins is α-synuclein (α-Syn), which forms insoluble protein deposits in Parkinson's disease and other synucleinopathies. The majority of cases of Parkinson's disease occur fairly late in life and even early-onset variants of the disease caused by mutations to α-Syn occur towards the end of the lifespan for prehistoric man. This suggests a lack of evolutionary pressure to prevent protein aggregation in animals with similar or shorter lifespans. However, α-Syn is also found in animals with notably longer lifespans. Here, we tested the aggregation propensity of α-Syn sequences from short- and longer-lived animals at a range of evolutionary distances from humans. We find that in general longer-lived animals display slower α-Syn aggregation kinetics and the formation of smaller and less uniform fibrils. Overall, our data indicate that some evolutionary pressure may have existed for preventing α-Syn aggregation, but that pressure was lost in the more recent branch of shorter-lived animals containing humans.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500340"},"PeriodicalIF":2.6,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264934","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

Pathological Disulfide bond Crosslinking: Molecular Insights into Amyloidogenesis and Diseases Progression. 病理二硫键交联：淀粉样蛋白发生和疾病进展的分子观察。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-06-10 DOI: 10.1002/cbic.202500316

Yun Kyung Kim, Dong Min Kang, Nataliia Lukianenko, Ja-Hyun Baik, Sungsu Lim

引用次数: 0

Probing Unspecific Peroxygenases for Non-Natural Nitrene Chemistry. 探索非特异性过氧酶在非天然亚硝基化学中的作用。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-06-06 DOI: 10.1002/cbic.202500332

Pascal Püllmann, Dominik Homann, Lewis Thomas-Hargreaves

引用次数: 0

Synthesis of Chemically Diverse siRNA-Lipid Conjugates Enabled by Reversible Adsorption to Solid Support (RASS). 固体载体（RASS）可逆吸附合成化学多样性sirna -脂类偶联物。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-06-05 DOI: 10.1002/cbic.202500169

Albert Kakkis, Linzhongyi Sun, Zhijie Xie, Maya Qaddourah, Philip E Dawson, Brittany B Sanchez, Brandon J Orzolek, Florence M Brunel, Joseph R Stock, Robert V Kolakowski, Ilia Korboukh, Jens C Leon

{"title":"Synthesis of Chemically Diverse siRNA-Lipid Conjugates Enabled by Reversible Adsorption to Solid Support (RASS).","authors":"Albert Kakkis, Linzhongyi Sun, Zhijie Xie, Maya Qaddourah, Philip E Dawson, Brittany B Sanchez, Brandon J Orzolek, Florence M Brunel, Joseph R Stock, Robert V Kolakowski, Ilia Korboukh, Jens C Leon","doi":"10.1002/cbic.202500169","DOIUrl":"https://doi.org/10.1002/cbic.202500169","url":null,"abstract":"Small interfering RNAs (siRNAs) directly regulate gene expression and are, thus, attractive targets for clinical development to treat a variety of human diseases. While \"naked\" siRNAs are poor drug candidates, numerous chemical modifications of siRNAs have been developed to lower nuclease-sensitivity, increase cellular uptake, and enable cell-type-specific targeting. One class of modifications that has received attention is postsynthetic lipidation, as the pharmacokinetics of siRNA-lipid conjugates have been found to vary significantly based on the structure of the lipid moiety. While postsynthetic lipidation is a facile and effective means to render siRNAs more drug-like, most of these modifications occur in a single-step and in aqueous solution, engendering a limited chemical space. Herein, reversible adsorption of oligos onto a cationic solid support is demonstrated to facilitate postsynthetic, multistep modifications of single- and double-stranded siRNA in neat organic solvent to obtain siRNA-lipid conjugates with lipid moieties (e.g., long-chain alkyl thioethers, polyfluorinated biphenyl groups) that are challenging to incorporate using established postsynthetic lipidation procedures. RASS represents a rapid and convenient approach to generate siRNA-lipid conjugates encompassing a broad chemical space and ultimately a promising avenue to accelerate the discovery of potent siRNA therapeutics.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2500169"},"PeriodicalIF":2.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144223813","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

Advancing the Exploration of the Ubiquitin-like Protein FUBI with Synthetic Chemical Tools. 利用合成化学工具推进对泛素样蛋白FUBI的研究

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-06-04 DOI: 10.1002/cbic.202500321

Francesca D'Amico, Cami Talavera Ormeño, Shivanganie Poeran, Jimmy Akkermans, Rayman T N Tjokrodirijo, Bharath Sampadi, Peter van Veelen, Aysegul Sapmaz, Monique Priscilla Catharina Mulder

{"title":"Advancing the Exploration of the Ubiquitin-like Protein FUBI with Synthetic Chemical Tools.","authors":"Francesca D'Amico, Cami Talavera Ormeño, Shivanganie Poeran, Jimmy Akkermans, Rayman T N Tjokrodirijo, Bharath Sampadi, Peter van Veelen, Aysegul Sapmaz, Monique Priscilla Catharina Mulder","doi":"10.1002/cbic.202500321","DOIUrl":"https://doi.org/10.1002/cbic.202500321","url":null,"abstract":"The Ubiquitin-like protein FUBI is encoded in humans by the FAU gene, whose down-regulation in prostate, ovarian and breast cancer is significantly associated with poor prognosis. Despite its implications in disease progression, the regulatory mechanisms orchestrated by FUBI remain elusive. To address this knowledge gap, we developed a linear synthetic platform to generate FUBI chemical tools, enabling the site-specific incorporation of unnatural building blocks and the introduction of fluorophores, tags and reactive warheads. Using this platform, we created activity-based probes for FUBI conjugation and deconjugation enzymes, validating them in cell lysate-based assays and proteomics. Additionally, we synthesized a triazole-linked Di-FUBI to investigate FUBI chain modulators. Among the proteomics hits, we identify IMPDH1 and the deubiquitinase UCHL3 as novel Di-FUBI specific interactors. Further characterization revealed that Di-FUBI inhibits UCHL3 cleavage activity in a concentration-dependent manner, suggesting a novel regulatory interplay between UCHL3 and FUBI. Collectively, these tools demonstrate the versatility of our synthetic FUBI platform, advancing the characterization of FUBI-related enzymes in the ongoing efforts to decipher the complex code of Ubiquitin-like signaling.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500321"},"PeriodicalIF":2.6,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214466","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: Engineering and Structural Elucidation of a Sac7d-Derived IgG Fc-Specific Affitin and Its Application for the Light-Controlled Affinity Purification of Antibodies (ChemBioChem 11/2025) 封面：sac7d衍生的IgG fc特异性粘附蛋白的工程和结构解析及其在抗体光控亲和纯化中的应用（ChemBioChem 11/2025）

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-06-04 DOI: 10.1002/cbic.202581101

Felix Veitl, Andreas Eichinger, Peter Mayrhofer, Markus R. Anneser, Mauricio Testanera, Kilian Rauscher, Matthias Lenz, Arne Skerra

引用次数: 0

Enhancing Peptide Cyclization: Unveiling the Key Roles of Coupling Reagents and Heat for Optimal Results. 增强肽环化：揭示偶联试剂和热对最佳结果的关键作用。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-06-04 DOI: 10.1002/cbic.202500375

Kim Gaudin, Alexie Bobe, Vijay Kumar Pal, Céline Corcelle, Kelton Rodrigues de Souza, Cecilia Menard-Moyon

{"title":"Enhancing Peptide Cyclization: Unveiling the Key Roles of Coupling Reagents and Heat for Optimal Results.","authors":"Kim Gaudin, Alexie Bobe, Vijay Kumar Pal, Céline Corcelle, Kelton Rodrigues de Souza, Cecilia Menard-Moyon","doi":"10.1002/cbic.202500375","DOIUrl":"https://doi.org/10.1002/cbic.202500375","url":null,"abstract":"Cyclic peptides offer several advantages over their linear counterparts, including enhanced structural stability due to their rigid conformation and increased resistance to enzymatic proteolysis. Additionally, their ring structure and constrained conformation reduce the entropic cost upon binding to receptors and other biological targets, leading to higher binding affinity and specificity. However, peptide macrocyclization is often synthetically challenging due to reduced entropy, oligomer formation, and C-terminal epimerization. The conventional approach for synthesizing cyclic peptides involves the direct coupling of amine and carboxyl termini in solution phase, using protected side-chain peptides and coupling reagents. Despite this, improving the efficiency of head-to-tail cyclization remains a key challenge. In this study, we optimized the cyclization of a de novo octapeptide composed of alternating l- and d-amino acids. The impact of various factors on the cyclization was examined, including coupling reagents, temperature, heating, chaotropic agents, solvent and concentration. This investigation has not only led to the identification of efficient cyclization conditions, but it also provides a valuable framework for the cyclization of challenging peptide sequences. The insights gained in this study contribute to the field of peptide chemistry, expanding the understanding of peptide cyclization reactions, which could accelerate the development of cyclic peptide-based therapeutics.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500375"},"PeriodicalIF":2.6,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214467","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

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