Preclinical Evaluation of Azabenzimidazole-Based PET Radioligands for γ-8 Dependent Transmembrane AMPA Receptor Regulatory Protein Imaging
Chembiochem. 2024 Jan 16:e202300813. doi: 10.1002/cbic.202300813. Online ahead of print.ABSTRACTAMPA glutamate receptors (AMPARs) play a pivotal role in excitatory neurotransmission, particularly in the hippocampus where the TARP γ-8 subunit is enriched and serves as a target for emerging anti-epileptic drugs. To enable in vivo visualization of TARP γ-8 distribution and expression by positron emission tomography (PET), this study focuses on the development of novel 18F-labeled TARP γ-8 inhibitors and their corresponding precursors, stemming from the azabenzimidazole scaffold. The resulting radioligands [18F]TARP-2204 an...
Source: Chembiochem - January 16, 2024 Category: Biochemistry Authors: Jiahui Chen Yinlong Li QingZhen Yu Jimmy S Patel Xin Zhou Kuo Zhang Jian Rong Chunyu Zhao Ahmad F Chaudhary Wei Zhang Chunyang Bi Zhendong Song April T Davenport Ahmed Haider James B Daunais Lee Collier Hongjie Yuan Steven Liang Source Type: research
Heterochiral modifications enhance robustness and function of DNA in living human cells
Chembiochem. 2024 Jan 16:e202300755. doi: 10.1002/cbic.202300755. Online ahead of print.ABSTRACTOligonucleotide therapeutics are becoming increasingly important as more are approved by the FDA, both for treatment and vaccination. Similarly, dynamic DNA nanotechnology is a promising technique that can be used to sense exogenous input molecules or endogenous biomarkers and integrate the results of multiple sensing reactions in situ via a programmed cascade of reactions. The combination of these two technologies could be highly impactful in biomedicine by enabling smart oligonucleotide therapeutics that can autonomously sense...
Source: Chembiochem - January 16, 2024 Category: Biochemistry Authors: Tracy L Mallette Diane S Lidke Matthew R Lakin Source Type: research
Unveiling PET Hydrolase Surface Dynamics through Fluorescence Microscopy
Chembiochem. 2024 Jan 15:e202300661. doi: 10.1002/cbic.202300661. Online ahead of print.ABSTRACTPET hydrolases are an emerging class of enzymes that are being heavily researched for their use in bioprocessing polyethylene terephthalate (PET). While work has been done in studying the binding of PET oligomers to the active site of these enzymes, the dynamics of PET hydrolases binding to a bulk PET surface is an unexplored area. Here, methods were developed for total internal reflection fluorescence (TIRF) microscopy and fluorescence recovery after photobleaching (FRAP) microscopy to study the adsorption and desorption dynami...
Source: Chembiochem - January 15, 2024 Category: Biochemistry Authors: A P Rennison A Nousi P Westh R Marie M S M øller Source Type: research
Amylose Dimerization in Solution Can Be Studied Using a Model System
Chembiochem. 2024 Jan 14:e202300832. doi: 10.1002/cbic.202300832. Online ahead of print.ABSTRACTAmylose, the linear polymer of α-1,4-linked glucopyranose units, is known to crystallize as a parallel double helix, but evidence of this duplex forming in solution has remained elusive for decades. We show how the dimerization of short amylose chains can be detected in solution using NMR spectroscopy when the glucans are labeled at the reducing-end with an aromatic moiety that overcomes chemical shift degeneracy leading to distinct signals for the single-stranded and duplex amylose. A set of α-1,4 glucans with varying lengths...
Source: Chembiochem - January 14, 2024 Category: Biochemistry Authors: Charlotte Nybro Dansholm Sebastian Meier Sophie R Beeren Source Type: research
DMSO-Related Effects on Ligand-Binding Properties of Lysine Methyltransferases G9a and SETD8
Chembiochem. 2024 Jan 11:e202300809. doi: 10.1002/cbic.202300809. Online ahead of print.ABSTRACTBeing the standard solvent for preparing stock solutions of compounds for drug discovery, DMSO is always present in assay buffers in concentrations ranging from 0.1 % to 5 % (v/v). Even at the lowest concentrations, DMSO-containing solutions can have significant effects on individual proteins and possible pitfalls cannot be eliminated. Herein, we used two protein systems, the lysine methyltransferases G9a/KMT1 C and SETD8/KMT5 A, to study the effects of DMSO on protein stability and on the binding of the corresponding inhibitors...
Source: Chembiochem - January 11, 2024 Category: Biochemistry Authors: Alessandra Feoli Giuliana Sarno Sabrina Castellano Gianluca Sbardella Source Type: research
Molybdenum-Copper Antagonism In Metalloenzymes And Anti-Copper Therapy
Chembiochem. 2024 Jan 11:e202300679. doi: 10.1002/cbic.202300679. Online ahead of print.ABSTRACTThe connection between 3d (Cu) and 4d (Mo) via the "Mo-S-Cu" unit is called Mo-Cu antagonism. Biology offers case studies of such interactions in metalloproteins such as Mo/Cu-CO Dehydrogenases (Mo/Cu-CODH), and Mo/Cu Orange Protein (Mo/Cu-ORP). The CODH significantly maintains the CO level in the atmosphere below the toxic level by converting it to non-toxic CO2 for respiring organisms. Several models were synthesized to understand the structure-function relationship of these native enzymes. However, this interaction was first ...
Source: Chembiochem - January 11, 2024 Category: Biochemistry Authors: Biplab K Maiti Isabel Moura Jos é J G Moura Source Type: research
Illuminating the Path to Enhanced Bioimaging by Phosphole-based Fluorophores
In this study, we introduce phosphole-based fluorophores that surpass existing options like dansyl chloride. The reactive S-Cl bond in chlorosulfonylimino-5-phenylphosphole derivatives allows rapid and direct coupling to peptides making the fluorophores easily introducible to peptides. This coupling process occurs under mild conditions, demonstrated for [F7 ,P34 ]-NPY and its shorter analogues. Peptides linked with our fluorophores exhibit similar receptor activation to the control peptide, while maintaining high stability and low toxicity, making them ideal biolabeling reagents. In fluorescence microscopy experiments, the...
Source: Chembiochem - January 11, 2024 Category: Biochemistry Authors: Mareike Schenk Nils K önig Evamarie Hey-Hawkins Annette G Beck-Sickinger Source Type: research
Design and Evaluation of PROTACs Targeting Acyl Protein Thioesterase 1
Chembiochem. 2024 Jan 9:e202300736. doi: 10.1002/cbic.202300736. Online ahead of print.ABSTRACTPROTAC linker design remains mostly an empirical task. We employed the PRosettaC computational software in the design of sulfonyl-fluoride-based PROTACs targeting acyl protein thioesterase 1 (APT1). The software efficiently generated ternary complex models from empirically-designed PROTACs and suggested alkyl linkers to be the preferred type of linker to target APT1. Western blotting analysis revealed efficient degradation of APT1 and activity-based protein profiling showed remarkable selectivity of an alkyl linker-based PROTAC a...
Source: Chembiochem - January 10, 2024 Category: Biochemistry Authors: Lu ís A R Carvalho B árbara B Sousa Daniel Zaidman Hannah Kiely-Collins Gon çalo J L Bernardes Source Type: research
In-Bridge Stereochemistry: A Determinant of Stapled Peptide Conformation and Activity
Chembiochem. 2024 Jan 8:e202300747. doi: 10.1002/cbic.202300747. Online ahead of print.ABSTRACTPeptide side chain stapling has been proven to be an effective strategy for fine-tuning peptide properties. This innovative approach leads to the creation of stapled peptides characterized by stabilized α-helical conformations, enhanced protein-binding affinity, improved cell permeability, superior enzymatic stability, and numerous other advantages. Extensive research has explored the impact of various stapling bridges on the properties of these peptides, with limited investigation into the influence of bridge chirality, until v...
Source: Chembiochem - January 9, 2024 Category: Biochemistry Authors: Jingyi Zhang Suwei Dong Source Type: research
In-Bridge Stereochemistry: A Determinant of Stapled Peptide Conformation and Activity
Chembiochem. 2024 Jan 8:e202300747. doi: 10.1002/cbic.202300747. Online ahead of print.ABSTRACTPeptide side chain stapling has been proven to be an effective strategy for fine-tuning peptide properties. This innovative approach leads to the creation of stapled peptides characterized by stabilized α-helical conformations, enhanced protein-binding affinity, improved cell permeability, superior enzymatic stability, and numerous other advantages. Extensive research has explored the impact of various stapling bridges on the properties of these peptides, with limited investigation into the influence of bridge chirality, until v...
Source: Chembiochem - January 9, 2024 Category: Biochemistry Authors: Jingyi Zhang Suwei Dong Source Type: research
A facile and general tandem oligonucleotide synthesis methodology for DNA and RNA
Chembiochem. 2024 Jan 5:e202300870. doi: 10.1002/cbic.202300870. Online ahead of print.ABSTRACTTandem oligonucleotide synthesis (TOS) is an attractive strategy to increase automated oligonucleotide synthesis efficiency. TOS is accomplished via the introduction of an immolative linker within a single sequence composed of multiple oligonucleotide fragments. Here, we report the use of a commercially available building block, typically utilized for the chemical phosphorylation of DNA/RNA oligomers, to perform TOS. We show that the 2,2'-sulfonyldiethylene linker is efficiently self-immolated during the standard deprotection of ...
Source: Chembiochem - January 5, 2024 Category: Biochemistry Authors: Jagandeep S Saraya Derek O'Flaherty Source Type: research
Selection and Characterization of DNA Aptamers for Cytidine and Uridine
This study employs the library-immobilization capture-SELEX technique to isolate aptamers capable of selectively binding to cytidine and uridine. First, a selection was performed using a mixture of cytidine and uridine as the target. This selection led to the isolation of a highly selective aptamer for cytidine with a dissociation constant (Kd ) of 0.9 μM as determined by isothermal titration calorimetry (ITC). In addition, a dual-recognition aptamer was also discovered, which exhibited selective binding to both cytidine and uridine. Subsequently, a separate selection was carried out using uridine as the sole target, and ...
Source: Chembiochem - January 5, 2024 Category: Biochemistry Authors: Lide Gu Jiajie Zheng Yao Zhang Deli Wang Juewen Liu Source Type: research
A facile and general tandem oligonucleotide synthesis methodology for DNA and RNA
Chembiochem. 2024 Jan 5:e202300870. doi: 10.1002/cbic.202300870. Online ahead of print.ABSTRACTTandem oligonucleotide synthesis (TOS) is an attractive strategy to increase automated oligonucleotide synthesis efficiency. TOS is accomplished via the introduction of an immolative linker within a single sequence composed of multiple oligonucleotide fragments. Here, we report the use of a commercially available building block, typically utilized for the chemical phosphorylation of DNA/RNA oligomers, to perform TOS. We show that the 2,2'-sulfonyldiethylene linker is efficiently self-immolated during the standard deprotection of ...
Source: Chembiochem - January 5, 2024 Category: Biochemistry Authors: Jagandeep S Saraya Derek O'Flaherty Source Type: research
Selection and Characterization of DNA Aptamers for Cytidine and Uridine
This study employs the library-immobilization capture-SELEX technique to isolate aptamers capable of selectively binding to cytidine and uridine. First, a selection was performed using a mixture of cytidine and uridine as the target. This selection led to the isolation of a highly selective aptamer for cytidine with a dissociation constant (Kd ) of 0.9 μM as determined by isothermal titration calorimetry (ITC). In addition, a dual-recognition aptamer was also discovered, which exhibited selective binding to both cytidine and uridine. Subsequently, a separate selection was carried out using uridine as the sole target, and ...
Source: Chembiochem - January 5, 2024 Category: Biochemistry Authors: Lide Gu Jiajie Zheng Yao Zhang Deli Wang Juewen Liu Source Type: research
A facile and general tandem oligonucleotide synthesis methodology for DNA and RNA
Chembiochem. 2024 Jan 5:e202300870. doi: 10.1002/cbic.202300870. Online ahead of print.ABSTRACTTandem oligonucleotide synthesis (TOS) is an attractive strategy to increase automated oligonucleotide synthesis efficiency. TOS is accomplished via the introduction of an immolative linker within a single sequence composed of multiple oligonucleotide fragments. Here, we report the use of a commercially available building block, typically utilized for the chemical phosphorylation of DNA/RNA oligomers, to perform TOS. We show that the 2,2'-sulfonyldiethylene linker is efficiently self-immolated during the standard deprotection of ...
Source: Chembiochem - January 5, 2024 Category: Biochemistry Authors: Jagandeep S Saraya Derek O'Flaherty Source Type: research
