ChemBioChem最新文献_第10页

The Position of Indole Methylation Controls the Structure, DNA Binding, and Cellular Functions of Mithramycin SA-Trp Analogues 吲哚甲基化位置控制米霉素SA-Trp类似物的结构、DNA结合和细胞功能。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-04-17 DOI: 10.1002/cbic.202401084

Caixia Hou, Suhas Bhosale, Kazuto Yasuda, Rajesh Yetirajam, Markos Leggas, Jürgen Rohr, Oleg V. Tsodikov

{"title":"The Position of Indole Methylation Controls the Structure, DNA Binding, and Cellular Functions of Mithramycin SA-Trp Analogues","authors":"Caixia Hou, Suhas Bhosale, Kazuto Yasuda, Rajesh Yetirajam, Markos Leggas, Jürgen Rohr, Oleg V. Tsodikov","doi":"10.1002/cbic.202401084","DOIUrl":"10.1002/cbic.202401084","url":null,"abstract":"Mithramycin (MTM) is a polyketide anticancer natural product, which functions by noncovalent binding to DNA in the minor groove without intercalation, resulting in inhibiting transcription at G/C-rich promoters. MTM is a potent inhibitor of cancer cells, such as Ewing sarcoma, driven by abnormal fusions involving E26 transformation-specific (ETS) family transcription factors friend leukemia integration 1 (FLI1) and ETS-related gene (ERG). However, MTM is rather toxic and nonselective; therefore, safer, selective analogues of MTM are required for use in the clinic as anticancer drugs. Herein, by using a combination of X-ray crystallographic, biophysical, and cell and molecular biological techniques, the structural and functional consequences of 3-side chain methylation at positions 5, 6, and 7 of the indole ring of the potent analogue MTM SA-Trp are explored. The conformation of the analogues in complexes with DNA, their DNA binding function, cytotoxicity, selectivity, and potency as transcription antagonists depended on the position of the methylation. MTM SA-5-methyl-Trp emerged as the most selective analogue, presumably due to the right balance of the DNA binding and the solvent exposure of the 3-side chain. This study demonstrates that minor chemical changes can have strong effects in analogue development and paves the way to further development of next-generation MTM analogues.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 10","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957802","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: The Biarylitides: Understanding the Structure and Biosynthesis of a Fascinating Class of Cytochrome P450 Modified RiPP Natural Products (ChemBioChem 7/2025) 封面：The biarylides：了解一类迷人的细胞色素P450修饰的RiPP天然产物的结构和生物合成（ChemBioChem 7/2025）

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-04-16 DOI: 10.1002/cbic.202580701

Leo Padva, Jemma Gullick, Laura J. Coe, Mathias H. Hansen, James J. De Voss, Max Crüsemann, Max J. Cryle

引用次数: 0

Purine Chemistry in the Early RNA World at the Origins of Life: From RNA and Nucleobases Lesions to Current Key Metabolic Routes 生命起源早期RNA世界中的嘌呤化学：从RNA和核碱基病变到当前的关键代谢途径。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-04-16 DOI: 10.1002/cbic.202500035

Jean-Luc Décout, Marie-Christine Maurel

{"title":"Purine Chemistry in the Early RNA World at the Origins of Life: From RNA and Nucleobases Lesions to Current Key Metabolic Routes","authors":"Jean-Luc Décout, Marie-Christine Maurel","doi":"10.1002/cbic.202500035","DOIUrl":"10.1002/cbic.202500035","url":null,"abstract":"In early life, RNA probably played the central role and, in the corresponding RNA world, the main produced amino acids and small peptides had to react continuously with RNA, ribonucleos(t)ides and nucleobases, especially with purines. A RNA-peptide world and key metabolic pathways have emerged from the corresponding chemical modifications such as the translation process performed by the ribosome. Some interesting reactions of the purine bicycle and of the corresponding ribonucleos(t)ides are performed under plausible prebiotic conditions and described RNA chemical lesions are reviewed with the prospect to highlight their connection with some major steps of the purine and histidine biosynthetic pathways that are, in an intriguingly way, related through two key metabolites, adenosine 5′-triphosphate and the imidazole ribonucleotide 5-aminoimidazole-4-carboxamide ribonucleotide. Ring-opening reactions of purines stand out as efficient accesses to imidazole ribonucleotides and to formamidopyrimidine (Fapy) ribonucleotides suggesting that biosynthetic pathway’ first steps have emerged from RNA and ribonucleos(t)ide damages. Also, are summarized the works on the formation and catalytic properties, under plausible prebiotic conditions, of N6-derivatives of the purine base adenine as potential surrogates of histidine in catalysis accordingly to their structural relationship.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 11","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.202500035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Cover Feature: Boronic Acid-Linked Apo-Zinc Finger Protein for Ubiquitin Delivery in Live Cells (ChemBioChem 7/2025) 封面专题：用于活细胞中泛素传递的硼酸连接载脂蛋白锌指蛋白（ChemBioChem 7/2025）

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-04-16 DOI: 10.1002/cbic.202580702

Dr. Pritam Ghosh, Prof. Dr. Oliver Seitz

引用次数: 0

Structure–Affinity Relationship Analysis and Affinity Maturation of a Calprotectin-Binding Peptide 钙保护蛋白结合肽的结构-亲和关系分析及亲和成熟。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-04-16 DOI: 10.1002/cbic.202500071

Lluc Farrera-Soler, Che-Wei Hu, Benjamin Ricken, Cristina Díaz-Perlas, Christian-Benedikt Gerhold, Christian Heinis

{"title":"Structure–Affinity Relationship Analysis and Affinity Maturation of a Calprotectin-Binding Peptide","authors":"Lluc Farrera-Soler, Che-Wei Hu, Benjamin Ricken, Cristina Díaz-Perlas, Christian-Benedikt Gerhold, Christian Heinis","doi":"10.1002/cbic.202500071","DOIUrl":"10.1002/cbic.202500071","url":null,"abstract":"Peptide 3 is an 18-amino acid linear peptide binding with sub-micromolar affinity to the inflammation marker calprotectin. Its application in point-of-care diagnostic assays has shown promising results, yet improving its affinity for calprotectin could facilitate the development of sensitive and robust assays. Herein, a detailed structure–activity relationship analysis of Peptide 3 is reported to better understand the importance of each individual amino acid for the binding to calprotectin. Moreover, two different approaches have been followed here, one based on prolonging the peptide with random sequences and phage display selection, and one on screening chemically synthesized peptide variants containing non-canonical amino acids, to increase its binding affinity. Combining several mutations that enhance affinity by small factors yielded Peptide 4 binding human calprotectin with a KD of 39 ± 5 nM measured by surface plasmon resonance spectroscopy, which is a five-fold improvement compared to the previously reported Peptide 3.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 10","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954247","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

Probing Thrombosis Initiation with Lasso Peptide Variants as Inhibitors to the von Willebrand Protein-Collagen Interaction. 用套索肽变体作为血管性血友病蛋白-胶原相互作用抑制剂探测血栓形成。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-04-15 DOI: 10.1002/cbic.202500188

Danielle A Guarracino, Drew V Carson, Toby G Johnson, A James Link

引用次数: 0

Sulfur(IV) Chemistry-Based Peptide and Protein Late-Stage Modification 硫（IV）基于化学的肽和蛋白质后期修饰。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-04-15 DOI: 10.1002/cbic.202500234

Dongyan Yang, Zhijun Ruan, Shiliang He, Li Tang, Rui Wang, Chuan Wan

{"title":"Sulfur(IV) Chemistry-Based Peptide and Protein Late-Stage Modification","authors":"Dongyan Yang, Zhijun Ruan, Shiliang He, Li Tang, Rui Wang, Chuan Wan","doi":"10.1002/cbic.202500234","DOIUrl":"10.1002/cbic.202500234","url":null,"abstract":"The development of precise and controllable chemical modification tools for peptides and proteins represents a great challenge in elucidating their structure–activity relationships and regulatory mechanisms, as well as a powerful driver for advancing macromolecular therapeutic strategies. However, current technologies predominantly rely on irreversible covalent labeling or genetic encoding of unnatural amino acids, exhibiting significant limitations in reversible modification, in situ functional regulation, and adaptability to complex physiological environments. In recent years, breakthrough advancements in sulfur(IV) chemistry have provided a paradigm for the late-stage functionalization of peptides and proteins. Through synergistic innovations in sulfur(IV)-based reagent design, intermediate modulation, and bioorthogonal reactions, a more multifaceted modification toolbox has been progressively established, integrating site selectivity, condition responsiveness, and functional rescue. Providing current challenges and future perspectives in this field, this review focuses on sulfur(IV) chemistry-driven strategies for peptide and protein modification, as well as their applications in proximity-labeling strategies and drug delivery/therapeutic interventions.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 10","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953870","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

Characterization of the Cubamyces Menziesii Terpenome. 门氏立方菌萜烯的表征。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-04-14 DOI: 10.1002/cbic.202401083

Létitia Leydet, Julie Couillaud, Agnès Amouric, Elise Courvoisier-Dezord, Carole Avesque, Thierry Giardina, Mireille Attolini, Pierre Rousselot-Pailley, Katia Duquesne, Marie-Noelle Rosso, Gilles Iacazio

{"title":"Characterization of the Cubamyces Menziesii Terpenome.","authors":"Létitia Leydet, Julie Couillaud, Agnès Amouric, Elise Courvoisier-Dezord, Carole Avesque, Thierry Giardina, Mireille Attolini, Pierre Rousselot-Pailley, Katia Duquesne, Marie-Noelle Rosso, Gilles Iacazio","doi":"10.1002/cbic.202401083","DOIUrl":"https://doi.org/10.1002/cbic.202401083","url":null,"abstract":"Long-lasting polypore fungi are significant producers of terpene cyclases of high interest for medicinal or biotechnological applications. Following the 1000 Fungal Genomes initiative launched by the Joint Genome Institute, the genome of Cubamyces (C.) menziesii and identified 18 genes encoding sesquiterpene cyclases (STCs) is explored. In a search for robust catalysts suitable for practical applications, the 18 codon-optimized open reading frames are cloned and overproduced the C. menziesii STCs in Escherichia coli. In ten cases, the catalytically active enzyme is purified and tested with three chemically synthesized linear diphosphates: geranyl diphosphate, farnesyl diphosphate (FDP), and geranylgeranyl diphosphate. Only FDP proved to be a substrate for these 10 enzymes. The product specificity of all these enzymes is determined by (GC-MS) gas chromatography mass spectrometry and (NMR) nuclear magnetic resonance analysis. Among the 10 enzymes, four produced a predominant compound, four yielded two main compounds, and the remaining two acted as a multiproduct catalysts. This work sheds light on the potential sesquiterpenes involved in the chemical ecology of the polypore C. menziesii and provides evidence for the potential of Polyporales fungi in the identification of new sesquiterpene cyclase activities.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2401083"},"PeriodicalIF":2.6,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957656","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

Diversity of ThDP-Dependent Enzymes Forming Chiral Tertiary Alcohols. thdp依赖性酶形成手性叔醇的多样性。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-04-14 DOI: 10.1002/cbic.202500200

Daniela Bjarnesen, Lucrezia Lanza, Francesco Presini, Pier Paolo Giovannini, Michael Müller

{"title":"Diversity of ThDP-Dependent Enzymes Forming Chiral Tertiary Alcohols.","authors":"Daniela Bjarnesen, Lucrezia Lanza, Francesco Presini, Pier Paolo Giovannini, Michael Müller","doi":"10.1002/cbic.202500200","DOIUrl":"10.1002/cbic.202500200","url":null,"abstract":"Thiamine diphosphate (ThDP)-dependent enzymes are well known biocatalysts for CC bond-forming reactions. While this enzyme class is mainly investigated for the formation of acyloins of secondary alcohols, recent studies have expanded its scope to utilize ketones as electrophiles in asymmetric carboligation reactions for the formation of tertiary alcohols. Chiral tertiary alcohols are ubiquitous motifs in natural products and important building blocks for the synthesis of bioactive compounds. ThDP-dependent enzymes are emerging as one of the most promising classes of biocatalysts for synthesizing a wide range of products due to the variety of possible substrate combinations, accessible starting materials, high enantioselectivity, and advantageous self-regeneration of the catalytic ThDP cofactor. This review provides an overview of the ThDP-dependent enzymes (e.g., decarboxylase, DC; transketolase, TK; α-keto acid dehydrogenase 2, αKADH2) that form tertiary alcohols, focusing on the substrate scope and diversity of physiological functions. The available toolbox and the characterized reactions shall serve as a starting point for future studies. Inspired by nature, an even broader diversity of classes and substrate specificities is expected in this field.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2500200"},"PeriodicalIF":2.6,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959338","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

Antimicrobial Piano-Stool and Polypyridyl Ru(II) Complexes with Thiazolhidrazinylidene-Chroman-2,4-Dione: Tautomerism, Membrane Disruption, and Electron Transport Interference 抗菌钢琴粪便和多吡啶Ru（II）配合物与噻唑肼基-铬-2,4-二酮：互变异构、膜破坏和电子传递干扰。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-04-11 DOI: 10.1002/cbic.202401025

Fatlinda Rahmani, Gozde Demirci, Youri Cortat, Aurélien Crochet, Fabio Zobi

引用次数: 0