Month: December 2022

Tanaka, Masayoshi published the artcileAdenosine A_2B receptor down-regulates metabotropic glutamate receptor 5 in astrocytes during postnatal development, HPLC of Formula: 264622-53-9, the publication is Glia (2021), 69(11), 2546-2558, database is CAplus and MEDLINE.

Metabotropic glutamate receptor 5 (mGluR5) in astrocytes is a key mol. for controlling synapse remodeling. Although mGluR5 is abundant in neonatal astrocytes, its level is gradually down-regulated during development and is almost absent in the adult. However, in several pathol. conditions, mGluR5 re-emerges in adult astrocytes and contributes to disease pathogenesis by forming uncontrolled synapses. Thus, controlling mGluR5 expression in astrocyte is critical for several diseases, but the mechanism that regulates mGluR5 expression remains unknown. Here, we show that ATP (ATP)/adenosine-mediated signals down-regulate mGluR5 in astrocytes. First, in situ Ca2+ imaging of astrocytes in acute cerebral slices from post-natal day (P)7-P28 mice showed that Ca2+ responses evoked by (S)-3,5-dihydroxyphenylglycine (DHPG), a mGluR5 agonist, decreased during development, whereas those evoked by ATP or its metabolite, adenosine, increased. Second, ATP and adenosine suppressed expression of the mGluR5 gene, Grm5, in cultured astrocytes. Third, the decrease in the DHPG-evoked Ca2+ responses was associated with down-regulation of Grm5. Interestingly, among several adenosine (P1) receptor and ATP (P2) receptor genes, only the adenosine A2B receptor gene, Adora2b, was up-regulated in the course of development. Indeed, we observed that down-regulation of Grm5 was suppressed in Adora2b knockout astrocytes at P14 and in situ Ca2+ imaging from Adora2b knockout mice indicated that the A2B receptor inhibits mGluR5 expression in astrocytes. Furthermore, deletion of A2B receptor increased the number of excitatory synapse in developmental stage. Taken together, the A2B receptor is critical for down-regulation of mGluR5 in astrocytes, which would contribute to terminate excess synaptogenesis during development.

Glia published new progress about 264622-53-9. 264622-53-9 belongs to amides-buliding-blocks, auxiliary class GPCR/G Protein,Adenosine Receptor, name is N-(4-Acetylphenyl)-2-(4-(2,6-dioxo-1,3-dipropyl-2,3,6,9-tetrahydro-1H-purin-8-yl)phenoxy)acetamide, and the molecular formula is C14H31NO2, HPLC of Formula: 264622-53-9.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Metcalf, Gavin A. D. published the artcileAmplification-Free Detection of Circulating microRNA Biomarkers from Body Fluids Based on Fluorogenic Oligonucleotide-Templated Reaction between Engineered Peptide Nucleic Acid Probes: Application to Prostate Cancer Diagnosis, Computed Properties of 186046-83-3, the publication is Analytical Chemistry (Washington, DC, United States) (2016), 88(16), 8091-8098, database is CAplus and MEDLINE.

Highly abundant in cells, microRNAs (or miRs) play a key role as regulators of gene expression. A proportion of them are also detectable in biofluids making them ideal noninvasive biomarkers for pathologies in which miR levels are aberrantly expressed, such as cancer. Peptide nucleic acids (PNAs) are engineered uncharged oligonucleotide analogs capable of hybridizing to complementary nucleic acids with high affinity and high specificity. Herein, novel PNA-based fluorogenic biosensors have been designed and synthesized that target miR biomarkers for prostate cancer (PCa). The sensing strategy is based on oligonucleotide-templated reactions where the only miR of interest serves as a matrix to catalyze an otherwise highly unfavorable fluorogenic reaction. Validated in vitro using synthetic RNAs, these newly developed biosensors were then shown to detect endogenous concentrations of miR in human blood samples without the need for any amplification step and with minimal sample processing. This low-cost, quant., and versatile sensing technol. has been tech. validated using gold-standard RT-qPCR. Compared to RT-qPCR however, this enzyme-free, isothermal blood test is amenable to incorporation into low-cost portable devices and could therefore be suitable for widespread public screening.

Analytical Chemistry (Washington, DC, United States) published new progress about 186046-83-3. 186046-83-3 belongs to amides-buliding-blocks, auxiliary class Purine,Carboxylic acid,Amine,Benzene,Amide,Others,PNA,, name is 2-(N-(2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-2-(2-(((benzhydryloxy)carbonyl)amino)-6-oxo-5H-purin-9(6H)-yl)acetamido)acetic acid, and the molecular formula is C40H35N7O8, Computed Properties of 186046-83-3.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Wang, Sen-Lin published the artcileSynthesis and bioactivity of novel pyrazole oxime derivatives containing oxazole ring, Formula: C7H5Cl2NO, the publication is Chinese Chemical Letters (2015), 26(6), 672-674, database is CAplus.

A series of novel pyrazole oxime derivatives containing oxazole ring were designed and synthesized. The title compounds were structurally confirmed by ¹H NMR, ¹³C NMR spectra and elemental analyses. Preliminary bioassay results showed that some of the title compounds displayed promising fungicidal activity besides insecticidal and acaricidal activity. Particularly, compound 8c exhibited potent fungicidal activity against cucumber Pseudoperonospora cubensis beyond good insecticidal activity against Aphis craccivora and Nilaparvata lugens.

Chinese Chemical Letters published new progress about 2447-79-2. 2447-79-2 belongs to amides-buliding-blocks, auxiliary class Chloride,Amine,Benzene,Amide, name is 2,4-Dichlorobenzamide, and the molecular formula is C25H47NO8, Formula: C7H5Cl2NO.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Shrestha, Ritu published the artcileDual Peptide Nucleic Acid- and Peptide-Functionalized Shell Cross-Linked Nanoparticles Designed to Target mRNA toward the Diagnosis and Treatment of Acute Lung Injury, Related Products of amides-buliding-blocks, the publication is Bioconjugate Chemistry (2012), 23(3), 574-585, database is CAplus and MEDLINE.

In this work, multifunctional biosynthetic hybrid nanostructures were prepared and studied for their potential utility in the recognition and inhibition of mRNA sequences for inducible nitric oxide synthase (iNOS), which are overexpressed at sites of inflammation, such as in cases of acute lung injury. Shell cross-linked knedel-like polymer nanoparticles (SCKs) that present peptide nucleic acids, for binding to complementary mRNAs, and cell penetrating peptides (CPPs), to gain cell entry, along with fluorescent labels and sites for radiolabeling, were prepared by a series of robust, efficient, and versatile synthetic steps that proceeded from monomers to polymers to functional nanoparticles. Amphiphilic block graft copolymers having combinations of methoxy- and thioacetyl-terminated poly(ethylene glycol) (PEG) and DOTA-lysine units grafted from the backbone of poly(acrylic acid) (PAA) and extending with a backbone segment of poly(octadecyl acrylate-co-decyl acrylate) (P(ODA-co-DA)) were prepared by a combination of reversible addition-fragmentation chain transfer (RAFT) polymerization and chem. modification reactions, which were then used as the building blocks for the formation of well-defined SCKs decorated with reactive thiols accessible to the surface. Fluorescent labeling with Alexa Fluor 633 hydrazide was then accomplished by amidation with residual acrylic acid residues within the SCK shells. Finally, the PNAs and CPP units were covalently conjugated to the SCKs via Michael addition of thiols on the SCKs to maleimide units on the termini of PNAs and CPPs. Confirmation of the ability of the PNAs to bind selectively to the target iNOS mRNAs when tethered to the SCK nanoparticles was determined by in vitro competition experiments When attached to the SCKs having a hydrodynamic diameter of 60 ± 16 nm, the K_d values of the PNAs were ca. an order of magnitude greater than the free PNAs, while the mismatched PNA showed no significant binding.

Bioconjugate Chemistry published new progress about 186046-83-3. 186046-83-3 belongs to amides-buliding-blocks, auxiliary class Purine,Carboxylic acid,Amine,Benzene,Amide,Others,PNA,, name is 2-(N-(2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)ethyl)-2-(2-(((benzhydryloxy)carbonyl)amino)-6-oxo-5H-purin-9(6H)-yl)acetamido)acetic acid, and the molecular formula is C8H7ClO3, Related Products of amides-buliding-blocks.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Zheng, Yiwu published the artcileStabilizing p-Dithiobenzyl Urethane Linkers without Rate-Limiting Self-Immolation for Traceless Drug Release, Synthetic Route of 2418-95-3, the publication is ChemMedChem (2019), 14(12), 1196-1203, database is CAplus and MEDLINE.

Exploiting the redox sensitivity of disulfide bonds is a prevalent strategy in targeted prodrug designs. In contrast to aliphatic disulfides, p-thiobenzyl-based disulfides have rarely been used for prodrug designs, given their intrinsic instability caused by the low pK_a of aromatic thiols. Here, we examined the interplay between steric hindrance and the low-pK_a effect on thiol-disulfide exchange reactions and uncovered a new thiol-disulfide exchange process for the self-immolation of p-thiobenzyl-based disulfides. We observed a central leaving group shifting effect in the α,α-dimethyl-substituted p-dithiobenzyl urethane linkers (DMTB linkers), which leads to increased disulfide stability by more than two orders of magnitude, an extent that is significantly greater than that observed with typical aliphatic disulfides. In particular, the DMTB linkers display not only high stability, but also rapid self-immolation kinetics due to the low pK_a of the aromatic thiol, which can be used as a general and robust linkage between targeting reagents and cytotoxic drugs for targeted prodrug designs. The unique and promising stability characteristics of the present DMTB linker will likely inspire the development of novel targeted prodrugs to achieve traceless release of drugs into cells.

ChemMedChem published new progress about 2418-95-3. 2418-95-3 belongs to amides-buliding-blocks, auxiliary class Chiral,Carboxylic acid,Amine,Aliphatic hydrocarbon chain,Ester,Amino acide derivatives, name is H-Lys(Boc)-OH, and the molecular formula is C9H10O4, Synthetic Route of 2418-95-3.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Xie, Jianwei published the artcileTransition-metal-free decarboxylative amidation of aryl α-keto acids with diphenylphosphoryl azide: new avenue for the preparation of primary aryl amides, Recommanded Product: 2,4-Dichlorobenzamide, the publication is Youji Huaxue (2020), 40(12), 4284-4289, database is CAplus.

In this paper, a novel transition-metal-free decarboxylative amidation of (heteroaryl)aryl α-keto acids ArC(O)C(O)OH (Ar = 2,4-dichlorophenyl, naphthalen-2-yl, thiophen-2-yl, etc.) with diphenylphosphoryl azide (DPPA) under mild conditions has been developed. The reaction proceeded smoothly to afford the corresponding primary (heteroaryl)aryl amide products ArC(O)NH₂ in good to excellent yields under air and showed excellent functional group tolerance. Gram-scale reaction was also performed to produce the desired product in high yield. In addition, the mechanism of the present reaction was investigated.

Youji Huaxue published new progress about 2447-79-2. 2447-79-2 belongs to amides-buliding-blocks, auxiliary class Chloride,Amine,Benzene,Amide, name is 2,4-Dichlorobenzamide, and the molecular formula is C12H10O4S, Recommanded Product: 2,4-Dichlorobenzamide.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Huang, Guopu published the artcileA degradable, broad-spectrum and resistance-resistant antimicrobial oligoguanidine as a disinfecting and therapeutic agent in aquaculture, Formula: C4H6F3NOS, the publication is Polymer Chemistry (2022), 13(23), 3539-3551, database is CAplus.

The threat of antibiotic resistance to community healthcare and the global economy has raised extensive concern, and the over-use of antibiotics in animal husbandry plays a significant role in the occurrence and spread of resistance genes. An emerging solution for the above problem is the development of antimicrobial peptides (AMPs) and their mimics as alternative disinfectants in agriculture and aquaculture. These antibacterial agents usually exhibit excellent potency and a low drug resistance generation rate, but are highly cytotoxic to eukaryotes and thus post safety concerns. Here, we report our solution to this problem by introducing degradable linkers in oligoguanidine-based antimicrobial peptidomimetics with a dual-selective mechanism of action. With both bacterial membrane and DNA targeting capability, the hit peptidomimetic exhibited higher therapeutic indexes and synergistic effects with other antibiotics, while its fast antimicrobial kinetics and low resistance rate were maintained. In addition, the added degradable feature improved the biocompatibility and environmental sustainability of this material. The oligoguanidine-based hit peptidomimetic also showed good activity in vivo, as it did not cause observable toxicity in zebrafish, and it could significantly improve the survival rate of zebrafish in a scratch wound infection model.

Polymer Chemistry published new progress about 1869-45-0. 1869-45-0 belongs to amides-buliding-blocks, auxiliary class Trifluoromethylated Building Blocks, name is 2,2,2-Trifluoro-N-(2-mercaptoethyl)acetamide, and the molecular formula is C4H6F3NOS, Formula: C4H6F3NOS.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Smith, Kirk published the artcileMetabolic signatures of regulation by phosphorylation and acetylation, Recommanded Product: 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, the publication is iScience (2022), 25(1), 103730, database is CAplus and MEDLINE.

Acetylation and phosphorylation are highly conserved posttranslational modifications (PTMs) that regulate cellular metabolism, yet how metabolic control is shared between these PTMs is unknown. Here we analyze transcriptome, proteome, acetylome, and phosphoproteome datasets in E. coli, S. cerevisiae, and mammalian cells across diverse conditions using CAROM, a new approach that uses genome-scale metabolic networks and machine learning to classify targets of PTMs. We built a single machine learning model that predicted targets of each PTM in a condition across all three organisms based on reaction attributes (AUC>0.8). Our model predicted phosphorylated enzymes during a mammalian cell-cycle, which we validate using phosphoproteomics. Interpreting the machine learning model using game theory uncovered enzyme properties including network connectivity, essentiality, and condition-specific factors such as maximum flux that differentiate targets of phosphorylation from acetylation. The conserved and predictable partitioning of metabolic regulation identified here between these PTMs may enable rational rewiring of regulatory circuits.

iScience published new progress about 1011557-82-6. 1011557-82-6 belongs to amides-buliding-blocks, auxiliary class Epigenetics,Sirtuin, name is 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide, and the molecular formula is C5H5NO3S, Recommanded Product: 4-(tert-Butyl)-N-((4-(5-(dimethylamino)pentanamido)phenyl)carbamothioyl)benzamide.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Nieland, Thomas J. F. published the artcileIdentification of the Molecular Target of Small Molecule Inhibitors of HDL Receptor SR-BI Activity, Application In Synthesis of 321673-30-7, the publication is Biochemistry (2008), 47(1), 460-472, database is CAplus and MEDLINE.

Scavenger receptor, class B, type I (SR-BI), controls high-d. lipoprotein (HDL) metabolism by mediating cellular selective uptake of lipids from HDL without the concomitant degradation of the lipoprotein particle. We previously identified in a high-throughput chem. screen of intact cells five compounds (BLT-1-5) that inhibit SR-BI-dependent lipid transport from HDL, but do not block HDL binding to SR-BI on the cell surface. Although these BLTs are widely used to examine the diverse functions of SR-BI, their direct target(s), SR-BI itself or some other component of the SR-BI pathway, has not been identified. Here we show that SR-BI in the context of a membrane lipid environment is the target of BLT-1, -3, -4, and -5. The anal. using intact cells and an in vitro system of purified SR-BI reconstituted into liposomes was aided by information derived from structure-activity relationship (SAR) anal. of the most potent of these BLTs, the thiosemicarbazone BLT-1. We found that the sulfur atom of BLT-1 was crucially important for its inhibitory activity, because changing it to an oxygen atom resulted in the isostructural, but essentially inactive, semicarbazone derivative BLT-1s.c. SAR anal. also established the importance of BLT-1’s hydrophobic tail. BLTs and their corresponding inactive compounds can be used to explore the mechanism and function of SR-BI-mediated selective lipid uptake in diverse mammalian exptl. models. Consequently, BLTs may help determine the therapeutic potential of SR-BI-targeted pharmaceutical drugs.

Biochemistry published new progress about 321673-30-7. 321673-30-7 belongs to amides-buliding-blocks, auxiliary class Immunology/Inflammation,Scavenger receptor, name is [(2-Hexylcyclopentylidene)amino]thiourea, and the molecular formula is C12H23N3S, Application In Synthesis of 321673-30-7.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics

Khandaka, Himanshu published the artcileAerobic Cu and amine free Sonogashira and Stille couplings of aryl bromides/chlorides with a magnetically recoverable Fe₃O₄@SiO₂ immobilized Pd(II)-thioether containing NHC, Recommanded Product: 2-Chloroacetamide, the publication is Tetrahedron Letters (2021), 152844, database is CAplus.

Two value added C-C cross coupling reactions; Sonogashira and Stille couplings were achieved at milder conditions in the catalytic presence of a magnetically recoverable heterogeneous catalyst Fe₃O₄@SiO₂ immobilized Pd(II)-thioether containing NHC. The catalyst was earlier reported for Suzuki-Miyaura reaction and as an extension of its catalytic efficiency, the Stille and Sonogashira cross coupling reactions under aerobic condition had been explored in present report. The Sonogashira coupling of aryl bromides and terminal alkynes produced an excellent yield (∼96% at 0.25 mol% Pd) of the desired coupling product under copper and amines free conditions. Moreover, an excellent Stille coupling of readily available and more latent aryl chlorides and trialkylstannane was obtained (yields up to 95% at 0.25 mol% Pd) in absence of toxic fluorides additives. The broad substrate scope of the catalyst for both the coupling reactions and the magnetically recoverable feature of catalyst made this reaction highly desirable for industrial applications of present heterogeneous catalysis.

Tetrahedron Letters published new progress about 79-07-2. 79-07-2 belongs to amides-buliding-blocks, auxiliary class Chloride,Amine,Aliphatic hydrocarbon chain,Amide,Inhibitor, name is 2-Chloroacetamide, and the molecular formula is C2H4ClNO, Recommanded Product: 2-Chloroacetamide.

Referemce:
https://en.wikipedia.org/wiki/Amide,
Amide – an overview | ScienceDirect Topics