ChemBioChem最新文献_第7页

Harnessing Synthetic Riboswitches for Tunable Gene Regulation in Mammalian Cells.

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-02-24 DOI: 10.1002/cbic.202401015

Rushikesh M Khadake, Vaani Arora, Payal Gupta, Ambadas B Rode

引用次数: 0

Quantification of Propargylated RNA Nucleosides After Metabolic Labeling Via the Methylation Pathway.

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-02-24 DOI: 10.1002/cbic.202400986

Nadine A Kueck, Sabine Hüwel, Arne Hoffmann, Andrea Rentmeister

{"title":"Quantification of Propargylated RNA Nucleosides After Metabolic Labeling Via the Methylation Pathway.","authors":"Nadine A Kueck, Sabine Hüwel, Arne Hoffmann, Andrea Rentmeister","doi":"10.1002/cbic.202400986","DOIUrl":"10.1002/cbic.202400986","url":null,"abstract":"RNA modifications are involved in numerous biological processes and vary in different cell types. Methylation is the most widespread type of RNA modification and occurs via S-adenosyl-L-methionine (SAM). We recently developed a metabolic labeling approach based on intracellular formation of a clickable SAM analog (SeAdoYn) and demonstrated its use in mapping methyltransferase (MTase) target sites in mRNA from HeLa cells. Here we investigate how metabolic labeling via the clickable SAM analog modifies four different nucleosides in RNA of HEK293T in comparison to HeLa cells. We find that HEK293T cells retain higher cell viability upon feeding the clickable metabolic SAM precursor. In poly(A)+ RNA we find high Aprop/A levels (0.04 %) and in total RNA (but not poly(A)+ RNA) we detect prop3C, which had not been detected previously in HeLa cells. We discuss the findings in the context of data from the literature with respect to mRNA half-lives in cancer and non-cancer cell lines and suggest that CMTr2 is most likely responsible for the high Aprop level in poly(A)+ RNA.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202400986"},"PeriodicalIF":2.6,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490236","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

Glyoxalase 2 Coordinates de Novo Serine Metabolism. 乙二醛酶 2 协调新丝氨酸的生物合成。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-02-23 DOI: 10.1002/cbic.202401086

Marissa N Trujillo, Erin Q Jennings, Dominique O Farrera, Naoya Kitamura, Colin C Anderson, Sarah Gehrke, Julie A Reisz, Mogens Johannsen, James R Roede, Angelo D'Alessandro, James J Galligan

{"title":"Glyoxalase 2 Coordinates de Novo Serine Metabolism.","authors":"Marissa N Trujillo, Erin Q Jennings, Dominique O Farrera, Naoya Kitamura, Colin C Anderson, Sarah Gehrke, Julie A Reisz, Mogens Johannsen, James R Roede, Angelo D'Alessandro, James J Galligan","doi":"10.1002/cbic.202401086","DOIUrl":"10.1002/cbic.202401086","url":null,"abstract":"Phosphoglycerate dehydrogenase (PHGDH) is the first enzyme in de novo Ser biosynthesis. Numerous metabolic pathways rely on Ser as a precursor, most notably one-carbon metabolism, glutathione biosynthesis, and de novo nucleotide biosynthesis. To facilitate proliferation, many cancer cells shunt glycolytic flux through this pathway, placing PHGDH as a metabolic liability and feasible therapeutic target for the treatment of cancer. Herein, we demonstrate the post-translational modification (PTM) of PHGDH by lactoylLys. These PTMs are generated through a non-enzymatic acyl transfer from the glyoxalase cycle intermediate, lactoylglutathione (LGSH). Knockout of the primary LGSH regulatory enzyme, glyoxalase 2 (GLO2), results in increased LGSH and resulting lactoylLys modification of PHGDH. These PTMs reduce enzymatic activity, resulting in a marked reduction in intracellular Ser. Using stable isotope tracing, we demonstrate reduced flux through the de novo Ser biosynthetic pathway. Collectively, these data identify PHGDH as a target for modification by lactoylLys, resulting in reduced enzymatic activity and reduced intracellular Ser.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202401086"},"PeriodicalIF":2.6,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481816","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

Unveiling the Architecture of Human Fibrinogen: A Full-Length Structural Model.

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-02-22 DOI: 10.1002/cbic.202400425

Romina Medeiros, Jorge Cantero, Graciela Borthagaray, Margot Paulino

{"title":"Unveiling the Architecture of Human Fibrinogen: A Full-Length Structural Model.","authors":"Romina Medeiros, Jorge Cantero, Graciela Borthagaray, Margot Paulino","doi":"10.1002/cbic.202400425","DOIUrl":"10.1002/cbic.202400425","url":null,"abstract":"Fibrinogen is a protein involved in the haemostasis process playing a central role by forming the fibrin clot. An understanding of protein structure is vital to determining biological function. Despite many studies on the fibrin polymerization process, its molecular mechanism remains elusive mainly due to the absence of a full-length three-dimensional model of human fibrinogen. Amino- and carboxyl-terminal regions of the three pairs of chains that form this molecule are missing in the crystallographic structure, being the carboxyl-terminal of the Aα chain the most affected with a section of more than 400 amino acids missing. To have a full structure of the fibrinogen molecule would allow the creation of a model of protofibril, shedding light into the fibrin formation process through computational techniques such as molecular dynamics simulations. Absent regions were explored using homology modelling and coarse-grained molecular dynamics simulations. Later on, the model was refined and stabilized with atomistic molecular dynamic simulations. In the present study, we obtained the first realistic full-length structure of fibrinogen, with features in accordance with previous results obtained by experimental techniques.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202400425"},"PeriodicalIF":2.6,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476171","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

Biomimetic Recognition of SARS-CoV-2 Receptor-Binding Domain N-Glycans by an Antiviral Synthetic Receptor.

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-02-21 DOI: 10.1002/cbic.202500106

Carlo Santambrogio, Mirco Toccafondi, Lorena Donnici, Elisa Pesce, Raffaele De Francesco, Renata Grifantini, Erika Ponzini, Francesco Milanesi, Marco Fragai, Cristina Nativi, Stefano Roelens, Rita Grandori, Oscar Francesconi

引用次数: 0

From Genes to Molecules: The Fusarium PKS16 Gene Cluster facilitates the biosynthesis of proliferapyrones. 从基因到分子：镰刀菌 PKS16 基因簇促进了丙磺舒的生物合成。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-02-21 DOI: 10.1002/cbic.202401039

Anna K Atanasoff-Kardjalieff, Katharina Steinert, Klaus Bergander, Svetlana Kalinina, Lena Studt-Reinhold

{"title":"From Genes to Molecules: The Fusarium PKS16 Gene Cluster facilitates the biosynthesis of proliferapyrones.","authors":"Anna K Atanasoff-Kardjalieff, Katharina Steinert, Klaus Bergander, Svetlana Kalinina, Lena Studt-Reinhold","doi":"10.1002/cbic.202401039","DOIUrl":"https://doi.org/10.1002/cbic.202401039","url":null,"abstract":"Ascomycete fungi of the genus Fusarium are found in manifold ecological niches and thus pursue several lifestyles. On average, individual Fusarium species have the genetic capability to produce 50 natural products (NPs), which are in general thought to improve the fungus's fitness in defined environments. This also includes NPs with toxic potential (mycotoxins) contaminating food and feed sources. Recent research has shown that the production of NPs is tightly regulated on the transcriptional level and depends on the delicate balance between the deposition and removal of histone marks. Within this study, we show that the expression of the prior cryptic Fusarium PKS16 biosynthetic gene cluster (BGC) greatly depends on modifications at histone 3 lysine 27 (H3K27). By combining molecular-, chemical-, and bioinformatic analyses we show that the PKS16 BGC from F. fujikuroi B14 (FfB14) consists of nine genes, including a positively acting pathway-specific transcription factor, which although absent in some fusaria, functions in activating other PKS16 cluster genes. Moreover, we linked the PKS16 BGC to the biosynthesis of proliferapyrone (PRO) B, an isomer of the recently isolated PRO A.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202401039"},"PeriodicalIF":2.6,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143472002","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

Interactive 3D Objects Enhance Scientific Communication of Structural Data

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-02-20 DOI: 10.1002/cbic.202500036

Daniel Mokos, Bastian Daniel

{"title":"Interactive 3D Objects Enhance Scientific Communication of Structural Data","authors":"Daniel Mokos, Bastian Daniel","doi":"10.1002/cbic.202500036","DOIUrl":"10.1002/cbic.202500036","url":null,"abstract":"In scientific communication about three-dimensional structures, creating two-dimensional representations is standard practice. These representations often suffer from the drawback of losing potential information due to dimensionality reduction. Several options exist to present, share and publish 3D figures, however based on recent publications they are not widely utilized. Here we present simple ways to preserve the three-dimensionality of the structure by the creation of a custom-made model in GLTF format that is generated in the same workflow as the conventional figures. They can be published alongside a given manuscript with minimal additional effort to the authors, but a huge impact on the communicative power of the manuscript concerning the three-dimensional features of the reported structures. The scripts we adapted and published for this purpose open up new possibilities for the illustrator and allow the viewer to access the full three-dimensionality of the published structure. In future, this can simplify the publication process of protein structures or other models and be a valuable tool for scientific communication in digital or printed form.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 6","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.202500036","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456449","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

Small Molecule Fluorescent Probes for Glutathione S-Transferase.

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-02-19 DOI: 10.1002/cbic.202400994

Pingping Lu, Huiting Huang, Jia Liu, Yixuan Cao, Sheng Hua Liu, Jun Yin

引用次数: 0

Mitochondria-Targeted Temozolomide Probe for Overcoming MGMT-Mediated Resistance in Glioblastoma

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-02-19 DOI: 10.1002/cbic.202400935

Daniel Szames, Dr. Shana O. Kelley

{"title":"Mitochondria-Targeted Temozolomide Probe for Overcoming MGMT-Mediated Resistance in Glioblastoma","authors":"Daniel Szames, Dr. Shana O. Kelley","doi":"10.1002/cbic.202400935","DOIUrl":"10.1002/cbic.202400935","url":null,"abstract":"Temozolomide (Tmz) is a DNA methylating agent used for the treatment of glioblastoma multiforme (GBM). Resistance to Tmz in GBM is caused by the DNA direct repair enzyme O6-methylguanine DNA methyltransferase (MGMT), which is expressed in ~50 % of GBM tumours. It has yet to be confirmed that MGMT acts within mitochondria to repair mitochondrial DNA (mtDNA), and in this report we discuss the development of a novel mitochondria-targeted temozolomide probe (mtTmz) for evading MGMT-mediated resistance. Through conjugation of Tmz to a mitochondria-penetrating peptide (MPP), exclusive mitochondrial localization was achieved, and the probe retained alkylation activity demonstrated by chemical and DNA-based assays. Absence of nuclear DNA damage was assessed by detecting γH2AX foci. mtTmz demonstrated efficient cell killing capabilities independent of MGMT status in GBM cells as determined by cell viability assays. It was determined using a Proteinase K digestion assay that MGMT does not translocate to mitochondria in response to mtTmz treatment, and RT-qPCR analysis demonstrated that mtTmz does not induce MGMT gene expression compared to Tmz. The results reported highlight both the potential of mitochondrial targeting of Tmz and mitochondria as a therapeutic target in MGMT-expressing GBM.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"26 6","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.202400935","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143447797","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

Conjugation of Human N-Glycans Improves the Drug Properties of Existing Peptides and Proteins.

IF 2.6 4区生物学

ChemBioChem Pub Date : 2025-02-19 DOI: 10.1002/cbic.202401066

Yuji Nishiuchi, Sofia Elouali, Masato Noguchi, Hirofumi Ochiai

{"title":"Conjugation of Human N-Glycans Improves the Drug Properties of Existing Peptides and Proteins.","authors":"Yuji Nishiuchi, Sofia Elouali, Masato Noguchi, Hirofumi Ochiai","doi":"10.1002/cbic.202401066","DOIUrl":"10.1002/cbic.202401066","url":null,"abstract":"Glycosylation is one of the most ubiquitous post-translational modifications observed in peptides and proteins. It affects the structural and functional characteristics of these macromolecules, thereby exerting a profound influence on a multitude of biological processes. N-Glycans are expected to be a beneficial modifier for increasing the solubility and in vivo half-life, and reducing the aggregation and immunogenicity of native bioactive peptides and proteins, which have seen limited clinical utility due to their short blood half-life and unsuitable physicochemical properties. Chemoselective glycosylation reactions that can be conducted post-synthesis and in aqueous conditions are a promising strategy for the high-throughput development of peptide/protein drugs. This \"glycoconjugation\" approach is particularly advantageous in that manipulation of glycan protecting groups is not necessary, thereby allowing conjugation reactions to be carried out between target molecules and unprotected glycans. By providing a single glycosylation profile, i. e., glycan structure, number, and position, glycoconjugation not only allows the beneficial properties of N-glycans to be exploited, but also facilitates the investigation of N-glycan function.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202401066"},"PeriodicalIF":2.6,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456447","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