Month: October 2022

Schroeder, Griffin M.; Dutta, Debapratim; Cavender, Chapin E.; Jenkins, Jermaine L.; Pritchett, Elizabeth M.; Baker, Cameron D.; Ashton, John M.; Mathews, David H.; Wedekind, Joseph E. published the artcile< Analysis of a preQ1-I riboswitch in effector-free and bound states reveals a metabolite-programmed nucleobase-stacking spine that controls gene regulation>, Recommanded Product: 7H-Purin-2-amine, the main research area is turnip yellow mosaic virus preQ1I riboswitch nucleobase gene regulation.

Riboswitches are structured RNA motifs that recognize metabolites to alter the conformations of downstream sequences, leading to gene regulation. To investigate this mol. framework, we determined crystal structures of a preQ1-I riboswitch in effector-free and bound states at 2.00 Å and 2.65 Å-resolution Both pseudoknots exhibited the elusive L2 loop, which displayed distinct conformations. Conversely, the Shine-Dalgarno sequence (SDS) in the S2 helix of each structure remained unbroken. The expectation that the effector-free state should expose the SDS prompted us to conduct solution experiments to delineate environmental changes to specific nucleobases in response to preQ1. We then used nudged elastic band computational methods to derive conformational-change pathways linking the crystallog.-determined effector-free and bound-state structures. Pathways featured: (i) unstacking and unpairing of L2 and S2 nucleobases without preQ1-exposing the SDS for translation and (ii) stacking and pairing L2 and S2 nucleobases with preQ1-sequestering the SDS. Our results reveal how preQ1 binding reorganizes L2 into a nucleobase-stacking spine that sequesters the SDS, linking effector recognition to biol. function. The generality of stacking spines as conduits for effector-dependent, interdomain communication is discussed in light of their existence in adenine riboswitches, as well as the turnip yellow mosaic virus ribosome sensor.

Nucleic Acids Research published new progress about 3′-Untranslated region Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, Recommanded Product: 7H-Purin-2-amine.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Tanis, Virginia M.; Venkatesan, Hariharan; Cummings, Maxwell D.; Albers, Michael; Kent Barbay, J.; Herman, Krystal; Kummer, David A.; Milligan, Cynthia; Nelen, Marina I.; Nishimura, Rachel; Schlueter, Thomas; Scott, Brian; Spurlino, John; Wolin, Ronald; Woods, Craig; Xue, Xiaohua; Edwards, James P.; Fourie, Anne M.; Leonard, Kristi published the artcile< 3-Substituted Quinolines as RORγt Inverse Agonists>, Quality Control of 1003-21-0, the main research area is quinoline derivative preparation ROR gamma t inverse agonist SAR; IL-17; Inverse agonist; RORγt; Retinoic acid-related orphan nuclear receptor gamma t; Th17.

We have previously reported the syntheses of a series of 3,6-disubstituted quinolines as modulators of the retinoic acid receptor-related orphan receptor gamma t (RORγt). These mols. are potent binders but are high mol. weight and they exhibited poor solubility at pH 2 and pH 7. This manuscript details our efforts at improving phys. chem. properties for this series of compounds by increasing the diversity at the 3-position (i.e. introducing heteroatoms and lowering the mol. weight). These efforts have led to mols. which are potent binders with improved solubility

Bioorganic & Medicinal Chemistry Letters published new progress about Drug design. 1003-21-0 belongs to class imidazoles-derivatives, and the molecular formula is C4H5BrN2, Quality Control of 1003-21-0.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Zhang, Patricia; Le, Chi “Chip”; MacMillan, David W. C. published the artcile< Silyl Radical Activation of Alkyl Halides in Metallaphotoredox Catalysis: A Unique Pathway for Cross-Electrophile Coupling>, Application In Synthesis of 1003-21-0, the main research area is alkyl halide coupling reaction aryl bromide metallaphotoredox catalyst tristrimethylsilylsilane.

A strategy for cross-electrophile coupling has been developed via the merger of photoredox and transition metal catalysis. In this report, we demonstrate the use of com. available tris(trimethylsilyl)silane with metallaphotoredox catalysis to efficiently couple alkyl bromides with aryl or heteroaryl bromides in excellent yields. We hypothesize that a photocatalytically generated silyl radical species can perform halogen-atom abstraction to activate alkyl halides as nucleophilic cross-coupling partners. This protocol allows the use of mild yet robust conditions to construct Csp3-Csp2 bonds generically via a unique cross-coupling pathway.

Journal of the American Chemical Society published new progress about Aryl bromides Role: RCT (Reactant), RACT (Reactant or Reagent). 1003-21-0 belongs to class imidazoles-derivatives, and the molecular formula is C4H5BrN2, Application In Synthesis of 1003-21-0.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Chen, Hu; Lei, Min; Hu, Lihong published the artcile< Synthesis of 1-aryl indoles via coupling reaction of indoles and aryl halides catalyzed by CuI/metformin>, Product Details of C4H5BrN2, the main research area is aryl indole preparation; Ullmann coupling indole aryl halide copper metformin catalyst.

Ullmann-type C-N coupling reaction has been developed for the synthesis of 1-aryl indole derivatives by indoles and aryl halides in the presence of CuI/metformin (CuI/Met) in DMF. This method is very easy, rapid, and high yielding reaction for the synthesis of 1-aryl indoles. In particular, the metformin, which is used as ligand, is inexpensive and nontoxic that is considered to be relatively environmentally benign.

Tetrahedron published new progress about Aryl halides Role: RCT (Reactant), RACT (Reactant or Reagent). 1003-21-0 belongs to class imidazoles-derivatives, and the molecular formula is C4H5BrN2, Product Details of C4H5BrN2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Cristofalo, Matteo; Kovari, Daniel; Corti, Roberta; Salerno, Domenico; Cassina, Valeria; Dunlap, David; Mantegazza, Francesco published the artcile< Nanomechanics of Diaminopurine-Substituted DNA>, Related Products of 452-06-2, the main research area is diaminopurine double strand DNA nanomechanics.

2,6-Diaminopurine (DAP) is a nucleobase analog of adenine. When incorporated into double-stranded DNA (dsDNA), it forms three hydrogen bonds with thymine. Rare in nature, DAP substitution alters the phys. characteristics of a DNA mol. without sacrificing sequence specificity. Here, we show that in addition to stabilizing double-strand hybridization, DAP substitution also changes the mech. and conformational properties of dsDNA. Thermal melting experiments reveal that DAP substitution raises melting temperatures without diminishing sequence-dependent effects. Using a combination of at. force microscopy (AFM), magnetic tweezer (MT) nanomech. assays, and CD spectroscopy, we demonstrate that DAP substitution increases the flexural rigidity of dsDNA yet also facilitates conformational shifts, which manifest as changes in mol. length. DAP substitution increases both the static and dynamic persistence length of DNA (measured by AFM and MT, resp.). In the static case (AFM), in which tension is not applied to the mol., the contour length of DAP-DNA appears shorter than wild-type (WT)-DNA; under tension (MT), they have similar dynamic contour lengths. At tensions above 60 pN, WT-DNA undergoes characteristic overstretching because of strand separation (tension-induced melting) and spontaneous adoption of a conformation termed S-DNA. Cyclic overstretching and relaxation of WT-DNA at near-zero loading rates typically yields hysteresis, indicative of tension-induced melting; conversely, cyclic stretching of DAP-DNA showed little or no hysteresis, consistent with the adoption of the S-form, similar to what has been reported for GC-rich sequences. However, DAP-DNA overstretching is distinct from GC-rich overstretching in that it happens at a significantly lower tension. In physiol. salt conditions, evenly mixed AT/GC DNA typically overstretches around 60 pN. GC-rich sequences overstretch at similar if not slightly higher tensions. Here, we show that DAP-DNA overstretches at 52 pN. In summary, DAP substitution decreases the overall stability of the B-form double helix, biasing toward non-B-form DNA helix conformations at zero tension and facilitating the B-to-S transition at high tension.

Biophysical Journal published new progress about Conformational transition. 452-06-2 belongs to class imidazoles-derivatives, and the molecular formula is C5H5N5, Related Products of 452-06-2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Ibrahim, Mansur; Malik, Imran; Mansour, Waseem; Sharif, Muhammad; Fettouhi, Mohammed; El Ali, Bassam published the artcile< Efficient N-heterocyclic carbene palladium(II) catalysts for carbonylative Suzuki-Miyaura coupling reactions leading to aryl ketones and diketones>, Recommanded Product: 5-Bromo-1-methyl-1H-imidazole, the main research area is palladium heterocyclic carbene pyridine complex catalyst preparation; aryl ketone diketone preparation; iodide aryl boronic acid palladium catalyst carbonylative Suzuki Miyaura.

New N, N’substituted imidazolium salts and their corresponding diiodopyridinepalladium(II) complexes I [R = CN, OMe] were successfully synthesized and characterized. Reactions of palladium iodide with the newly synthesized N, N’-substituted imidazolium iodides in pyridine afforded the corresponding new palladium-N-heterocyclic carbene pyridine complexes I in high yields. The new palladium(II) complex I [R = OMe] was characterized by single crystal X-ray diffraction anal. The Pd(II) ion was bonded to the nitrogen atom of the pyridine, the carbon atom of the NHC carbene ligand and two trans iodides resulting in distorted square planar geometry. The carbonylative Suzuki-Miyaura coupling reaction of aryl iodides with aryl boronic acids afforded aryl ketones II [R1 = H, CN, C(O)Me, OMe; R2 = H, OMe, COOH, etc.] and diketones III [R3 = H, CN, OMe] using palladium-N-heterocyclic carbene pyridine complexes.

Journal of Organometallic Chemistry published new progress about Aryl iodides Role: RCT (Reactant), RACT (Reactant or Reagent). 1003-21-0 belongs to class imidazoles-derivatives, and the molecular formula is C4H5BrN2, Recommanded Product: 5-Bromo-1-methyl-1H-imidazole.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Akiyama, Masayasu; Hara, Yukihiro; Tanabe, Minoru published the artcile< Effects of the substituents on the hydrolysis of 4-nitrophenyl acetate catalyzed by 2-substituted imidazoles>, Computed Properties of 36947-69-0, the main research area is hydrolysis kinetics nitrophenyl acetate imidazole; Broensted catalysis nitrophenyl acetate hydrolysis; mechanism hydrolysis nitrophenyl acetate imidazole; LFER hydrolysis nitrophenyl acetate.

A series of 2-alkyl and -(hydroxyalkyl)-substituted imidazoles catalyzed the hydrolysis of 4-nitrophenyl acetate. Activation parameters and D2O solvent isotope effects were determined for some of these imidazoles and showed that a bulky substituent decreased the rate of nucleophilic catalysis for most of the imidazoles. Anal. in terms of the Broensted catalysis law gave an extrapolated rate for each imidazole and indicated the importance of the steric effect relative to the parent compound Catalysis by 2-(1,1-dimethyl-2-hydroxyethyl)imidazole involved partial general base catalysis.

Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999) published new progress about Bronsted LFER. 36947-69-0 belongs to class imidazoles-derivatives, and the molecular formula is C7H12N2, Computed Properties of 36947-69-0.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Sun, Ping; Wang, Naixin; Zhao, Peng; Wang, Chao; Li, Hairu; Chen, Qi; Ge, Mang; Wang, Weiwei; Fang, Shaohong; Du, Guoqing; Zhang, Maomao; Tian, Jiawei published the artcile< Circulating Exosomes Control CD4+ T Cell Immunometabolic Functions via the Transfer of miR-142 as a Novel Mediator in Myocarditis>, Application of C30H30Cl2N6O2, the main research area is miR CD T cell immunometabolic function circulating exosome myocarditis; exosomes; experimental autoimmune myocarditis; glycolysis; miR-142.

The CD4+ T cells undergo immunometabolic activation to mount an immunogenic response during exptl. autoimmune myocarditis (EAM). Exosomes are considered key messengers mediating multiple T cell functions in autoimmune responses. However, the role of circulating exosomes in EAM immunopathogenesis and CD4+ T cell dysfunction remains elusive. Our objective was to elucidate the mechanism of action for circulating exosomes in EAM pathogenesis. We found that serum exosomes harvested from EAM mice induced CD4+ T cell immunometabolic dysfunction. Treatment with the exosome inhibitor GW4869 protected mice from developing EAM, underlying that exosomes are indispensable for the pathogenesis of EAM. Furthermore, by transfer of EAM exosomes, we confirmed that circulating exosomes initiate the T cell pathol. immune response, driving the EAM pathol. process. Mechanistically, EAM-circulating exosomes selectively loaded abundant microRNA (miR)-142. We confirmed methyl-CpG binding domain protein 2 (MBD2) and suppressor of cytokine signaling 1 (SOCS1) as functional target genes of miR-142. The miR-142/MBD2/MYC and miR-142/SOCS1 communication axes are critical to exosome-mediated immunometabolic turbulence. Moreover, the in vivo injection of the miR-142 inhibitor alleviated cardiac injury in EAM mice. This effect was abrogated by pretreatment with EAM exosomes. Collectively, our results indicate a newly endogenous mechanism whereby circulating exosomes regulateCD4+ T cell immunometabolic dysfunction and EAM pathogenesis via cargo miR-142.

Molecular Therapy published new progress about Apolipoprotein A-I Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Application of C30H30Cl2N6O2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Zhang, Jing; Tao, Yu; Cai, Renfei; Wang, Yao published the artcile< The miR-196a-5p-rich extracellular vesicles from trophoblasts induce M1 polarization of macrophages in recurrent miscarriage>, Application In Synthesis of 6823-69-4, the main research area is recurrent miscarriage miR196a5p extracellular vesicle trophoblast macrophage polarization.

Numerous studies have described the presence of crosstalk between trophoblasts and macrophages and the critical role it plays in recurrent miscarriage (RM). However, the mechanism of trophoblast-derived extracellular vesicle (EV) miRNAs and their interactions with decidual macrophages in the pathogenesis of RM remains unclear. MiRNA-seq was used to identify the differentially expressed miRNAs between RM patients and healthy controls. qPCR and in situ hybridization assays were performed to analyze the expression levels of miR-196a-5p in RM. THP-1 cells were treated with EVs, and qPCR and flow cytometry were performed to explore the polarization of macrophages. To explore the crosstalk between trophoblasts and macrophages, a coculture model and a series of cell function assays were performed. We first demonstrated that miR-196a-5p expression was higher in the cytotrophoblasts of villous tissues and plasma EVs from RM patients. miR-196a-5p derived from trophoblasts could be transferred into macrophages via EVs to induce M1 polarization via IκBα-mediated NF-κB pathway. Moreover, we found that M1 macrophages induced by EV miR-196a-5p derived from trophoblasts conversely regulated the proliferation, migration, and apoptosis of trophoblasts via TNF-α. This study indicated that trophoblast-derived EV miR-196a-5p was pos. associated with RM and functioned by regulating the crosstalk between trophoblasts and macrophages. These findings may attribute to identify a novel biomarker specific for RM.

Journal of Immunology Research published new progress about Apoptosis. 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Application In Synthesis of 6823-69-4.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem

Chen, Jialin; Zhou, Renpeng; Liang, Yimin; Fu, Xiujun; Wang, Danru; Wang, Chen published the artcile< Blockade of lncRNA-ASLNCS5088-enriched exosome generation in M2 macrophages by GW4869 dampens the effect of M2 macrophages on orchestrating fibroblast activation>, Application of C30H30Cl2N6O2, the main research area is monocytic cell skin fibroblast lncRNA exosome macrophage GW4869; TGF-β1; exosome inhibitor; glutaminase; hypertrophic scar; microRNA.

In hypertrophic scar (HS) formation, the type 2 immune response induces the alternatively activated macrophages (M2), which manipulate fibroblasts to differentiate into myofibroblasts with active biol. functions and proliferation. Myofibroblasts express α-smooth muscle actin (α-SMA) and synthesize and produce addnl. collagen type I and collagen type III, inducing HS formation. However, studies on the mechanism of M2 macrophage modulation are only based on the recognition of profibrotic factors such as TGF-β1 secreted by macrophages. The influence of exosomes from M2 macrophages on scar formation is still unknown. Both M2 macrophages and myofibroblasts highly express glutaminases (GLSs). GLS is a critical enzyme in glutaminolysis and is important for M2 macrophage and fibroblast polarization. In this study, we found that in a TGF-β1-stimulated coculture system, a long noncoding RNA (lncRNA) named lncRNA-ASLNCS5088 was enriched in M2 macrophage-derived exosomes. This lncRNA could be transferred with high efficiency to fibroblasts and acted as an endogenous sponge to adsorb microRNA-200c-3p, resulting in increased GLS and α-SMA expression. Pretreatment with GW4869, which impairs M2 macrophage exosome synthesis, ameliorated these pathol. changes in fibroblasts in vitro. Local injection in the late scar formation period with GW4869 reduced α-SMA+ fibroblasts and alleviated the fibrosis of tissue after wound healing in vivo.

FASEB Journal published new progress about Collagen type I Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 6823-69-4 belongs to class imidazoles-derivatives, and the molecular formula is C30H30Cl2N6O2, Application of C30H30Cl2N6O2.

Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem