ChemBioChem最新文献_第4页

Binding of Hg(I) and Hg(II) Ions to Amyloid-Beta (Aβ) Peptide Variants Affect Their Structure and Aggregation. Hg(I)和Hg（II）离子与淀粉样β (Aβ)肽变体的结合影响其结构和聚集。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-04-30 DOI: 10.1002/cbic.202500252

Elina Berntsson, Andra Noormägi, Kärt Padari, Jüri Jarvet, Astrid Gräslund, Margus Pooga, Peep Palumaa, Sebastian K T S Wärmländer

{"title":"Binding of Hg(I) and Hg(II) Ions to Amyloid-Beta (Aβ) Peptide Variants Affect Their Structure and Aggregation.","authors":"Elina Berntsson, Andra Noormägi, Kärt Padari, Jüri Jarvet, Astrid Gräslund, Margus Pooga, Peep Palumaa, Sebastian K T S Wärmländer","doi":"10.1002/cbic.202500252","DOIUrl":"https://doi.org/10.1002/cbic.202500252","url":null,"abstract":"Mercury (Hg) exposure is a possible risk factor for Alzheimer´s disease (AD). Some studies reported higher Hg levels in AD patients, but evidence is inconclusive. A mechanism linking Hg exposure to AD neuropathology remains to be found. The hallmark of AD brains is deposits of insoluble amyloid plaques consisting mainly of aggregated amyloid-β (Aβ) peptides. Here, we use transmission electron microscopy (TEM) and biophysical spectroscopy techniques to study in vitro interactions between inorganic Hg and pathologically relevant Aβ(1-40) and Aβ(4-40) variants and the Aβ(1-40)(H6A, H13A, H14A) mutant. For the first time, effect on Aβ aggregation of both Hg(I) and Hg(II) is compared. Hg(II) binds Aβ(1-40) with apparent binding affinity of 28±8 µM, at 20 °C in 20 mM MES buffer, pH 7.3. The N-terminal His6, His13 and His14 residues are involved in binding coordination. Hg(II) binding induces structural alterations (coil-coil interactions) in Aβ monomers positioned in membrane-mimicking SDS micelles. Equimolar amounts of either Hg(I) or Hg(II) inhibit normal Aβ fibrillation by directing aggregation towards formation of large amorphous aggregates. All these structural rearrangements may be relevant for the harmful Aβ aggregation processes involved in AD brain pathology. Inducing protein misfolding and aggregation might be a general toxic mechanism of mercury.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500252"},"PeriodicalIF":2.6,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954812","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

Exploiting SpyTag/SpyCatcher Technology To Design New Artificial Catalytic Copper Proteins. 利用SpyTag/SpyCatcher技术设计新型人工催化铜蛋白。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-04-29 DOI: 10.1002/cbic.202500208

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

{"title":"Exploiting SpyTag/SpyCatcher Technology To Design New Artificial Catalytic Copper Proteins.","authors":"Silvia Gentili, Francesca Miglioli, Valentina Borghesani, Gloria Spagnoli, Denise Bellotti, Davide Cavazzini, Remo Guerrini, Maurizio Remelli, Giovanni Maestri, Simone Ottonello, Angelo Bolchi, Matteo Tegoni","doi":"10.1002/cbic.202500208","DOIUrl":"https://doi.org/10.1002/cbic.202500208","url":null,"abstract":"Designing artificial metal binding sites within a protein is challenging since amino acid residues need to be placed in desired positions in the final construct and the use of non-natural amino acids is difficult. The alternative approach of directing the insertion of artificial metal coordination systems presents the difficulty of grafting such site in a single desired position. Spy protein is composed by a protein component (SpyCatcher) which binds spontaneously an oligopeptide (SpyTag) with formation of an isopeptide bond. We designed a SpyTag peptide equipped with an ATCUN (Amino Terminal Copper and Nickel) binding site which binds copper(II) with high femtomolar affinity both in the absence of SpyCatcher and in the reconstituted Spy construct. The Cu2+ ATCUN site in the reconstituted Spy protein presents a catalytic activity in ROS production, higher than that of the SpyTag peptide alone. This method offers a novel approach for constructing artificial metalloproteins by incorporating functional metal binding sites into a peptide, which can then be clicked onto its protein counterpart. The small size and modularity of this construct make it versatile for integration into other protein systems, eventually moving the complexity from a protein to a peptide and highlighting its potential for protein design.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500208"},"PeriodicalIF":2.6,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953842","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

Engineering of small ribozymes acting on RNA: What is needed to make a new function work with an existing catalyst? 作用于RNA的小核糖酶的工程：需要什么才能使新功能与现有催化剂协同工作？

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-04-28 DOI: 10.1002/cbic.202500213

Sabine Müller, Constanze Ebermann

{"title":"Engineering of small ribozymes acting on RNA: What is needed to make a new function work with an existing catalyst?","authors":"Sabine Müller, Constanze Ebermann","doi":"10.1002/cbic.202500213","DOIUrl":"https://doi.org/10.1002/cbic.202500213","url":null,"abstract":"The engineering of nucleic acids has been a longstanding objective in research, with the field gaining significant attention following the discovery of ribozymes in the early 1980s. Numerous nucleic acid catalysts have been developed to catalyze a wide range of reactions, and the structures of ribozymes have been modified to allow allosteric regulation by an external cofactor. All these constructs hold considerable promise for applications in biosensors for medical and environmental diagnostics, as well as in molecular tools for regulating cellular processes. In addition to the development of nucleic acid enzymes through in vitro selection, rational design offers a robust strategy for engineering ribozymes with customized properties. The structures and mechanisms of numerous nucleic acid catalysts have been thoroughly elucidated, making structural modulation a viable approach for designing their functional properties. Rational design necessitates the consideration of several parameters, and a range of tools is available to guide sequence design. In this review, we discuss sequence, structural, and functional design, primarily using the example of the hairpin ribozyme, to highlight the challenges and opportunities of rational nucleic acid enzyme engineering.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500213"},"PeriodicalIF":2.6,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957520","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

Challenges and achievements of peptide synthesis in aqueous and micellar media. 在水和胶束介质中合成肽的挑战和成就。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-04-27 DOI: 10.1002/cbic.202500099

Alessandro Angelini, Alessandro Scarso, Francesca Bordignon

引用次数: 0

Proline amide catalyzes formation of toxic crotonaldehyde from acetaldehyde under physiologically relevant conditions. 脯氨酸酰胺在生理相关条件下催化乙醛生成有毒的巴豆醛。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-04-25 DOI: 10.1002/cbic.202500138

Richard Hopkinson, Liam A Thomas, Vicki L Emms, Dipti Vashi, Louise Fairall, John W R Schwabe

引用次数: 0

Molecular Dynamics Simulations of Monomeric and Tetrameric Amyloid β_1-42 Peptides with d-Aspartic Acid Residues. 含d-天冬氨酸残基的单聚和四聚淀粉样蛋白β1-42肽的分子动力学模拟。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-04-25 DOI: 10.1002/cbic.202500171

Ayato Mizuno, Tomoki Nakayoshi, Kenju Inaoka, Ayumi Shingaki, Eiji Kurimoto, Koichi Kato, Akifumi Oda

{"title":"Molecular Dynamics Simulations of Monomeric and Tetrameric Amyloid β1-42 Peptides with d-Aspartic Acid Residues.","authors":"Ayato Mizuno, Tomoki Nakayoshi, Kenju Inaoka, Ayumi Shingaki, Eiji Kurimoto, Koichi Kato, Akifumi Oda","doi":"10.1002/cbic.202500171","DOIUrl":"https://doi.org/10.1002/cbic.202500171","url":null,"abstract":"Amyloid β1-42 (Aβ1-42) peptide includes three aspartic acid (Asp) residues. It is known that these Asp residues undergo stereoinversion to d-Asp in ageing tissues, a process that promotes β-sheet structure formation. In this study, the 3D structures of Aβ1-42 monomers and tetramers containing d-Asp residues are analyzed using molecular dynamics (MD) simulations. Seven types of mutants are generated by stereoinverting the three Asp residues, and monomer MD simulations are performed using an implicit solvent model for all seven mutants and the wild type. Following these implicit solvent simulations, tetramer MD simulations using explicit water molecules are conducted for the wild type and three mutants previously reported to form secondary structures in experimental studies. The MD simulations of Aβ1-42 monomers with implicit solvent successfully reproduced the trend of increased β-structure formation caused by D-Asp7 and d-Asp23. However, the effects of d-Asp1 are only captured in tetramer simulations using explicit water. These findings suggest that explicit water is necessary to accurately model peptide-peptide interactions and that multimer simulations are essential for investigating structural features, such as β-sheet formations and aggregation in proteins containing d-amino acids.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2500171"},"PeriodicalIF":2.6,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957921","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

Covalent Peptide-Graphene Conjugates for Enhanced Cell Spreading, Osteogenic Differentiation, and Angiogenesis in Bone Defects. 共价肽-石墨烯偶联物促进骨缺损细胞扩散、成骨分化和血管生成。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-04-25 DOI: 10.1002/cbic.202500210

Michelle Elise Wolf, Yaxuan Liu, Jason D Orlando, Jingzhi Zhou, Stefanie Arlene Sydlik

{"title":"Covalent Peptide-Graphene Conjugates for Enhanced Cell Spreading, Osteogenic Differentiation, and Angiogenesis in Bone Defects.","authors":"Michelle Elise Wolf, Yaxuan Liu, Jason D Orlando, Jingzhi Zhou, Stefanie Arlene Sydlik","doi":"10.1002/cbic.202500210","DOIUrl":"https://doi.org/10.1002/cbic.202500210","url":null,"abstract":"Traumatic bone injury is one of the most common injuries that require surgical intervention, and current treatments suffer severe drawbacks. Modern research in bone regeneration focuses on implants will support and enhance native tissue regeneration. One scaffold material that shows promise is graphene oxide (GO), a 2D nanomaterial made from oxidation of graphite. GO is biocompatible, strong, osteoinductive, is safely and slowly resorbed by the body, has a cheap, facile, and scalable synthesis, and is highly tailorable and functionalizable. The bioactivity of GO can be enhanced via functionalization with biomolecules such as peptides, proteins, and small molecules. Here, short peptides RGD, DGEA, and KKGHK are covalently bound to GO through a Claisen modification (CG) to create new functional graphenic materials that are cell-adhesive, osteogenic, and angiogenic, respectively. These peptide-Claisen graphenes (peptide-CGs) are found to be cytocompatible, to encourage cell spreading on the graphenic surface, to promote osteogenesis in stem cells, and to induce angiogenesis in vascular endothelial cells. They show promise as next-generation bone regeneration scaffolds by overcoming challenges frequently faced by bone regeneration scaffolds, namely retaining implanted and recruited cells, promoting their survival, proliferation, and differentiation, and ensuring a sufficient oxygen and nutrient supply to new tissue.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500210"},"PeriodicalIF":2.6,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953765","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

Exploring the Stability and Substrate Profile of Transaminase from Silicibacter pomeroyi with Ancestral Sequence Reconstruction. 用祖先序列重建法研究波默氏硅酸菌转氨酶的稳定性和底物特征。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-04-25 DOI: 10.1002/cbic.202500155

Luyao Zhao, Bhu-Bhud Thongrakon, Trishnamoni Gautom, Viktor Sahlberg, Per Berglund

{"title":"Exploring the Stability and Substrate Profile of Transaminase from Silicibacter pomeroyi with Ancestral Sequence Reconstruction.","authors":"Luyao Zhao, Bhu-Bhud Thongrakon, Trishnamoni Gautom, Viktor Sahlberg, Per Berglund","doi":"10.1002/cbic.202500155","DOIUrl":"https://doi.org/10.1002/cbic.202500155","url":null,"abstract":"Amine transaminases (ATAs), belonging to the class III transaminases within the superfamily of pyridoxal-5'-phosphate (PLP)-dependent enzymes, catalyze transamination reactions between amino donors and amino acceptors. These enzymes are particularly appealing for their role in the stereospecific synthesis of chiral amines. However, the stability of most ATAs is not satisfying, limiting their suitability for industrial applications. Among them, the amine transaminase from Silicibacter pomeroyi (Sp-ATA) has drawn attention due to its high activity and broad substrate scope under mild conditions and high pH. Nevertheless, maintaining the activity at higher temperatures presents a challenge. Previous research to enhance enzyme function through directed evolution has shown promise, yet predicting the cooperative effects of individual stabilizing mutations remains challenging. Computational approaches have been explored but often rely on structural information and are resource-intensive. An alternative strategy is ancestral sequence reconstruction (ASR), which is based on gene sequences to create a more or less artificial phylogenetic tree. This study aims to leverage ASR techniques to explore the thermostability, solvent tolerance, and substrate profile of Sp-ATA, to find highly stable transaminases. By using Sp-ATA as a template and incorporating insights from ancestral sequences, this strategy offers a promising approach for developing robust biocatalysts.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500155"},"PeriodicalIF":2.6,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143952372","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

Hybrid Molecules of Small Molecular and Peptidic HIV Fusion Inhibitors. 小分子和多肽HIV融合抑制剂的杂交分子。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-04-24 DOI: 10.1002/cbic.202500230

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

{"title":"Hybrid Molecules of Small Molecular and Peptidic HIV Fusion Inhibitors.","authors":"Kohei Tsuji, Takuya Kobayakawa, Peter Bolah, Soshi Nishimura, Tsutomu Murakami, Hirokazu Tamamura","doi":"10.1002/cbic.202500230","DOIUrl":"https://doi.org/10.1002/cbic.202500230","url":null,"abstract":"Since the membrane fusion step is the last chance to block the virus extracellularly, membrane fusion is an important target for anti-human immunodeficiency virus (HIV) agents. Previously, the dimeric derivatives of C34, which are contained in the HIV-1 envelope protein gp41 are found, linked by a disulfide bridge or a pegylated linker at its C-terminus have more potent anti-HIV activity than the C34 peptide monomer, and that bivalent inhibitors crosslinking two peptidomimetic small compounds have more potent anti-HIV activity than the parent small compounds. In the present study, the hybrids of small compounds (7-9) and peptides (SC34 (2) and SC22EK (3)) are designed as heterodimeric molecules (10-15) to compensate for the drawbacks of the above homodimeric molecules. Some hybrid molecules of small compounds (7-9) and peptide SC22EK (3) have remarkably higher anti-HIV activity than peptide SC22EK (3). Crosslinking small compounds and peptides (3) is found to be critical for an increase in anti-HIV activity. Hybrid molecules with small compounds and peptides are useful HIV-1 fusion inhibitors.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2500230"},"PeriodicalIF":2.6,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956407","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

Impact of Mutational Status on Intracellular Effects of Cell-Permeable CaaX Peptides in Pancreatic Cancer Cells. 突变状态对胰腺癌细胞可渗透CaaX肽细胞内效应的影响。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-04-24 DOI: 10.1002/cbic.202401076

Merlin Klußmann, Martin Matijass, Ines Neundorf

{"title":"Impact of Mutational Status on Intracellular Effects of Cell-Permeable CaaX Peptides in Pancreatic Cancer Cells.","authors":"Merlin Klußmann, Martin Matijass, Ines Neundorf","doi":"10.1002/cbic.202401076","DOIUrl":"https://doi.org/10.1002/cbic.202401076","url":null,"abstract":"Prenyltransferases add a lipid group to the cysteine of a CaaX motif of proteins. This posttranslational modification enables proteins to attach to membranes where they are essential hubs for signaling, trafficking, and apoptosis. Recently, cell-permeable CaaX-peptides are developed as possible tools to interfere with the prenylation machinery. These peptides cause cytotoxic effects, particularly in KRas mutant pancreatic cancer cells (PANC-1) in which they also alter downstream signaling of Ras proteins. Herein, the aim is to get more clues about the relevance of the mutational status of KRas. Therefore, the activity of CaaX-peptides in KRas wildtype BxPC-3 and KRas mutated PANC-1 cells is compared. CaaX-peptides differently influence these two cell lines, although they internalize pretty much to the same extent. Indeed, an altered KRas plasma membrane localization in PANC-1 cells is observed, probably induced by disturbed KRas prenylation based on the presence of CaaX-peptides. The impact of CaaX-peptides on KRas signaling is likely dependent on the KRas mutation in PANC-1 cells in which they further trigger effects on KRas-dependent regulators, e.g., Neurofibromin -1 (NF1) and son of sevenless homolog 1 (SOS1). All in all, CaaX peptides are identified as promising tools for studying and manipulating the function of therapeutically important prenylated proteins.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e2401076"},"PeriodicalIF":2.6,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144052854","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