U1 snrnp biogenesis deffects in neurodegenerative diseases
Chembiochem. 2024 Mar 9:e202300864. doi: 10.1002/cbic.202300864. Online ahead of print.ABSTRACTThe U1 small ribonucleoprotein (U1 snRNP) plays a pivotal role in the intricate process of gene expression, specifically within nuclear RNA processing. By initiating the splicing reaction and modulating 3'-end processing, U1 snRNP exerts precise control over RNA metabolism and gene expression. This ribonucleoparticle is abundantly present, and its complex biogenesis necessitates shuttling between the nuclear and cytoplasmic compartments. Over the past three decades, extensive research has illuminated the crucial connection betwee...
Source: Chembiochem - March 9, 2024 Category: Biochemistry Authors: Sebastien Campagne Source Type: research
U1 snrnp biogenesis deffects in neurodegenerative diseases
Chembiochem. 2024 Mar 9:e202300864. doi: 10.1002/cbic.202300864. Online ahead of print.ABSTRACTThe U1 small ribonucleoprotein (U1 snRNP) plays a pivotal role in the intricate process of gene expression, specifically within nuclear RNA processing. By initiating the splicing reaction and modulating 3'-end processing, U1 snRNP exerts precise control over RNA metabolism and gene expression. This ribonucleoparticle is abundantly present, and its complex biogenesis necessitates shuttling between the nuclear and cytoplasmic compartments. Over the past three decades, extensive research has illuminated the crucial connection betwee...
Source: Chembiochem - March 9, 2024 Category: Biochemistry Authors: Sebastien Campagne Source Type: research
U1 snrnp biogenesis deffects in neurodegenerative diseases
Chembiochem. 2024 Mar 9:e202300864. doi: 10.1002/cbic.202300864. Online ahead of print.ABSTRACTThe U1 small ribonucleoprotein (U1 snRNP) plays a pivotal role in the intricate process of gene expression, specifically within nuclear RNA processing. By initiating the splicing reaction and modulating 3'-end processing, U1 snRNP exerts precise control over RNA metabolism and gene expression. This ribonucleoparticle is abundantly present, and its complex biogenesis necessitates shuttling between the nuclear and cytoplasmic compartments. Over the past three decades, extensive research has illuminated the crucial connection betwee...
Source: Chembiochem - March 9, 2024 Category: Biochemistry Authors: Sebastien Campagne Source Type: research
Biophysical Investigation of RNA •DNA:DNA triple helix and RNA:DNA heteroduplex formation by the lncRNAs MEG3 and Fendrr
We present the investigations of the antiparallel triplex-forming lncRNA MEG3 targeting the gene TGFB2 and the parallel triplex-forming lncRNA Fendrr with its target gene Emp2. The thermodynamic properties of these oligonucleotides lead to concentration-dependent heterogeneous mixtures, where a DNA duplex, an RNA:DNA heteroduplex and an RNA•DNA:DNA triplex coexist and their relative populations are modulated in a temperature-dependent manner. The in vitro data provide a reliable readout of triplex structures, as RNA•DNA:DNA triplexes show distinct features compared to DNA duplexes and RNA:DNA heteroduplexes. Our experi...
Source: Chembiochem - March 8, 2024 Category: Biochemistry Authors: Nina M Krause Jasleen Kaur Bains Julius Blechar Christian Richter Irene Bessi Phillip Grote Matthias Leisegang Ralf P Brandes Harald Schwalbe Source Type: research
OptoProfilin: A Single Component Biosensor of Applied Cellular Stress
Chembiochem. 2024 Mar 8:e202400007. doi: 10.1002/cbic.202400007. Online ahead of print.ABSTRACTThe actin cytoskeleton is a biosensor of cellular stress and a potential prognosticator of human disease. In particular, aberrant cytoskeletal structures such as stress granules formed in response to energetic and oxidative stress are closely linked to ageing, cancer, cardiovascular disease, and viral infection. Whether these cytoskeletal phenomena can be harnessed for the development of biosensors for cytoskeletal dysfunction and, by extension, disease progression, remains an open question. In this work, we describe the design a...
Source: Chembiochem - March 8, 2024 Category: Biochemistry Authors: Noah Mann Jahiem T Hill Kenneth Wang Robert Hughes Source Type: research
High cell density cultivation combined with high specific enzyme activity: Cultivation protocol for the production of an amine transaminase from Bacillus megaterium in E. coli
Chembiochem. 2024 Mar 8:e202400006. doi: 10.1002/cbic.202400006. Online ahead of print.ABSTRACTHigh cell density cultivation is an established method for the production of various industrially important products such as recombinant proteins. However, these protocols are often not suitable for biocatalytic processes as often the focus lies on biomass production rather than high specific activities of the enzyme. In contrast, a range of shake flask protocols are well known with high specific activities but rather low cell densities. To overcome this gap, we established a tailor-made fed-batch protocol combining both aspects:...
Source: Chembiochem - March 8, 2024 Category: Biochemistry Authors: Berit Rothkranz Matthias Rieb Evelin Lisa Unrau Ilona Frindi-Wosch Johannes Hemmerich Torsten Sehl D örte Rother Source Type: research
Measuring Ligand-bound Protein Complexes with Proximity Labeling: A Practical Guide
Chembiochem. 2024 Mar 8:e202400073. doi: 10.1002/cbic.202400073. Online ahead of print.ABSTRACTIdentifying the drug-target interactome of small molecule therapeutics is essential for understanding the full pharmacological effects of a compound. These therapies often induce changes within the cellular proteome, leading to unexpected consequences such as changes in the targets complexation state or off-target interactions between the compound and additional proteins. Currently, unbiased target-ID approaches are being used to embark on this task. Here we provide an overview of the strengths and limitations of these methods, a...
Source: Chembiochem - March 8, 2024 Category: Biochemistry Authors: Pavitra Goyal Andrew J Tao Elizabeth J Mumby Justin G English Fleur M Ferguson Source Type: research
Bacterial hydrazine biosynthetic pathways featuring cupin/methionyl tRNA synthetase-like enzymes
Chembiochem. 2024 Mar 8:e202300874. doi: 10.1002/cbic.202300874. Online ahead of print.ABSTRACTNitrogen-Nitrogen (N-N) bond-containing functional groups in natural products and synthetic drugs play significant roles in exerting biological activities. The mechanisms of N-N bond formation in natural organic molecules have garnered increasing attention over the decades. Recent advances have illuminated various enzymatic and nonenzymatic strategies, and our understanding of natural N-N bond construction is rapidly expanding. A group of didomain proteins with zinc-binding cupin/methionyl-tRNA synthetase (MetRS)-like domains, al...
Source: Chembiochem - March 8, 2024 Category: Biochemistry Authors: Kenichi Matsuda Toshiyuki Wakimoto Source Type: research
Identification of a 2-aminobenzimidazole scaffold that potentiates gram-positive selective antibiotics against gram-negative bacteria
Chembiochem. 2024 Mar 7:e202400127. doi: 10.1002/cbic.202400127. Online ahead of print.ABSTRACTThe development of novel therapeutic approaches is crucial in the fight against multi-drug resistant (MDR) bacteria, particularly gram-negative species. Small molecule adjuvants that enhance the activity of otherwise gram-positive selective antibiotics against gram-negative bacteria have the potential to expand current treatment options. We have previously reported adjuvants based upon a 2-aminoimidazole (2-AI) scaffold that potentiate macrolide antibiotics against several gram-negative pathogens. Herein, we report the discovery ...
Source: Chembiochem - March 7, 2024 Category: Biochemistry Authors: Ansley M Nemeth Roberta J Melander Richard D Smith Robert K Ernst Christian Corey Melander Source Type: research
Identification of a 2-aminobenzimidazole scaffold that potentiates gram-positive selective antibiotics against gram-negative bacteria
Chembiochem. 2024 Mar 7:e202400127. doi: 10.1002/cbic.202400127. Online ahead of print.ABSTRACTThe development of novel therapeutic approaches is crucial in the fight against multi-drug resistant (MDR) bacteria, particularly gram-negative species. Small molecule adjuvants that enhance the activity of otherwise gram-positive selective antibiotics against gram-negative bacteria have the potential to expand current treatment options. We have previously reported adjuvants based upon a 2-aminoimidazole (2-AI) scaffold that potentiate macrolide antibiotics against several gram-negative pathogens. Herein, we report the discovery ...
Source: Chembiochem - March 7, 2024 Category: Biochemistry Authors: Ansley M Nemeth Roberta J Melander Richard D Smith Robert K Ernst Christian Corey Melander Source Type: research
A Dual-gene Reporter-amplifier Architecture for Enhancing the Sensitivity of Molecular MRI by Water Exchange
Chembiochem. 2024 Mar 4:e202400087. doi: 10.1002/cbic.202400087. Online ahead of print.ABSTRACTThe development of genetic reporters for magnetic resonance imaging (MRI) is essential for investigating biological functions in vivo. However, current MRI reporters have low sensitivity, making it challenging to create significant contrast against the tissue background, especially when only a small fraction of cells express the reporter. To overcome this limitation, we developed an approach for amplifying the sensitivity of molecular MRI by combining a chemogenetic contrast mechanism with a biophysical approach to increase water...
Source: Chembiochem - March 5, 2024 Category: Biochemistry Authors: Yimeng Huang Xinyue Chen Ziyue Zhu Arnab Mukherjee Source Type: research
Conversion of β-1,6-glucans to gentiobiose using an endo-β-1,6-glucanase PsGly30A from Paenibacillus sp. GKG
Chembiochem. 2024 Mar 5:e202400010. doi: 10.1002/cbic.202400010. Online ahead of print.ABSTRACTA plethora of di- and oligosaccharides isolated from the natural sources are used in food and pharmaceutical industry. An enzymatic hydrolysis of fungal cell wall β-glucans is a good alternative to produce the desired oligosaccharides with different functionalities, such as the flavour enhancer gentiobiose. We have previously identified PsGly30A as a potential yeast cell wall degrading β-1,6-glycosidase. The aim of this study is to characterise the PsGly30A enzyme, a member of the GH30 family, and to evaluate its suitability fo...
Source: Chembiochem - March 5, 2024 Category: Biochemistry Authors: Gediminas Plakys Nina Urbelien ė Gintaras Urbelis Justas Vaitek ūnas Linas Labanauskas Edita Ma žonienė Rolandas Me škys Source Type: research
Preclinical Evaluation of the Reversible Monoacylglycerol Lipase PET Tracer (R)-[ < sup > 11 < /sup > C]YH132: Application in Drug Development and Neurodegenerative Diseases
Chembiochem. 2024 Mar 5:e202300819. doi: 10.1002/cbic.202300819. Online ahead of print.ABSTRACTMonoacylglycerol lipase (MAGL) plays a crucial role in the degradation of 2-arachidonoylglycerol (2-AG), one of the major endocannabinoids in the brain. Inhibiting MAGL could lead to increased levels of 2-AG, which showed beneficial effects on pain management, anxiety, inflammation, and neuroprotection. In the current study, we report the characterization of an enantiomerically pure (R)-[11 C]YH132 as a novel MAGL PET tracer. It demonstrates an improved pharmacokinetic profile compared to its racemate. High in vitro MAGL specific...
Source: Chembiochem - March 5, 2024 Category: Biochemistry Authors: Yingfang He Aro Delparente Caitlin V M L Jie Claudia Keller Roland Humm Dominik Heer Ludovic Collin Roger Schibli Luca Gobbi Uwe Grether Linjing Mu Source Type: research
Reversible Influence of Hemipiperazine Photochromism on the Early Development of Zebrafish Embryo
This study explores the potential of controlling organismal development with light by using reversible photomodulation of activity in bioactive compounds. Specifically, our research focuses on plinabulin 1, an inhibitor of tubulin dynamics that contains a photochromic motif called hemipiperazine. The two isomeric forms, Z-1 and E-1, can partially interconvert with light, yet show remarkable thermal stability in darkness. The Z-isomer exhibits higher cytotoxicity due to stronger binding to α-tubulin's colchicine site. The less toxic E-1 form, considered a "pro-drug", can be isolated in vitro and stored. Upon activation by ...
Source: Chembiochem - March 5, 2024 Category: Biochemistry Authors: Angelika Seliwjorstow Masanari Takamiya Sepand Rastegar Zbigniew Pianowski Source Type: research
Synthesis and Macrodomain Binding of Gln-carba-ADPr-peptide
Chembiochem. 2024 Mar 5:e202300865. doi: 10.1002/cbic.202300865. Online ahead of print.ABSTRACTMono-ADP-ribosylation is a dynamic post-translational modification (PTM) with important roles in cell signalling. This modification occurs on a wide variety of amino acids, and one of the canonical modification sites within proteins is the side chain of glutamic acid. Given the transient nature of this modification (acylal linkage) and the high sensitivity of ADP-ribosylated glutamic acid, stabilized isosteres are required for structural and biochemical studies. Here, we report the synthesis of a mimic of ADP-ribosylated peptide ...
Source: Chembiochem - March 5, 2024 Category: Biochemistry Authors: Sande B Engelsma Aurelio Pio Nardozza Pieter de Saint Aulaire Herman S Overkleeft Gijsbert A van der Marel Andreas G Ladurner Dmitri Filippov Source Type: research
