Category: 2418-95-3

Ongaro, Alberto published the artcileDesign and synthesis of a peptide derivative of ametantrone targeting the major groove of the d(GGCGCC)₂ palindromic sequence, Related Products of amides-buliding-blocks, the publication is New Journal of Chemistry (2020), 44(9), 3624-3631, database is CAplus.

In oncol., some DNA intercalating agents have been used in chemotherapy for years to eradicate cancer cells, but these drugs generally suffer from a lack of selectivity for malignant tissues and consequently induce major side-effects. We report herein the design and synthesis of an antitumor intercalating agent ametantrone complemented with two identical peptide arms including a central Lys residue in order to selectively target palindromic sequences of DNA of malignant cells. The peptide arms are linked to the ametantrone core through 1,2,3-triazole. According to our docking prediction, this compound should be double-stranded β-sheet structured, and it has been designed to interact with two guanine residues upstream from a central d(CpG)₂ intercalation site on each DNA strand, owing to the H-bonds involving the Lys terminal side chain ammonium group of the peptide arms. This new ametantrone derivative has been obtained thanks to a convergent synthetic pathway, whose key steps were double nucleophilic substitution performed on the ametantrone core, followed by “double-site” 1,3-dipolar cycloaddition affording the 1,4-disubstituted triazole linker almost quant. Preliminary binding assays performed by mass spectrometry proved its accuracy for DNA palindromic sequences. The cytotoxicity of this compound was evaluated on three cancer cell lines and one healthy cell line, and compared to that of mitoxantone, a dihydroxylated analog of ametantrone. Such a peptide derivative was about ten-fold less cytotoxic than mitoxantrone on these cancer cell lines, but about fifty times less cytotoxic on healthy cells. This study could open new avenues towards the design of targeted intercalating agents.

New Journal of Chemistry 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 C11H22N2O4, Related Products of amides-buliding-blocks.

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

Rodrigues, Debora Munhoz published the artcileSynthesis, antitumor activity and in silico analyses of amino acid derivatives of artepillin C, drupanin and baccharin from green propolis, Synthetic Route of 2418-95-3, the publication is Bioorganic & Medicinal Chemistry (2021), 116372, database is CAplus and MEDLINE.

Breast cancer has the highest incidence and mortality in females, while prostate cancer has the second-highest incidence in males. Studies have shown that compounds from Brazilian green propolis have antitumor activities and can selectively inhibit the AKR1C3 enzyme, overexpressed in hormone-dependent prostate and breast tumors. Thus, in an attempt to develop new cytotoxic inhibitors against these cancers, three prenylated compounds, artepillin C, drupanin and baccharin, were isolated from green propolis to synthesize new derivatives via coupling reactions with different amino acids. All obtained derivatives were submitted to antiproliferative assays against four cancer cells (MCF-7, MDA MB-231, PC-3, and DU145) and two normal cell lines (MCF-10A and PNT-2) to evaluate their cytotoxicity. In general, the best activity was observed for compound 6e, derived from drupanin, which exhibited half-maximal inhibitory concentration (IC₅₀) of 9.6 ± 3 μM and selectivity index (SI) of 5.5 against MCF-7 cells. In silico studies demonstrated that these derivatives present coherent docking interactions and binding modes against AKR1C3, which might represent a possible mechanism of inhibition in MCF-7 cells.

Bioorganic & Medicinal Chemistry 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 C11H22N2O4, Synthetic Route of 2418-95-3.

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

Abdelkader, Elwy H. published the artcileGenetic Encoding of N⁶-(((Trimethylsilyl)methoxy)carbonyl)-L-lysine for NMR Studies of Protein-Protein and Protein-Ligand Interactions, Related Products of amides-buliding-blocks, the publication is Journal of the American Chemical Society (2021), 143(2), 1133-1143, database is CAplus and MEDLINE.

Trimethylsilyl (TMS) groups present outstanding NMR probes of biol. macromols. as they produce intense singlets in ¹H NMR spectra near 0 ppm, where few other proton resonances occur. We report a system for genetic encoding of N⁶-(((trimethylsilyl)methoxy)carbonyl)-L-lysine (TMSK) for site-specific incorporation into proteins. The system is based on pyrrolysyl-tRNA synthetase mutants, which deliver proteins with high yield and purity in vivo and in cell-free protein synthesis. As the TMS signal can readily be identified in 1D ¹H NMR spectra of high-mol. weight systems without the need of isotopic labeling, TMSK delivers an excellent site-specific NMR probe for the study of protein structure and function, which is both inexpensive and convenient. We demonstrate the utility of TMSK to detect ligand binding, measure the rate of conformational change, and assess protein dimerization by paramagnetic relaxation enhancement. In addition, we present a system for dual incorporation of two different unnatural amino acids (TMSK and O-tert-butyl-tyrosine) in the same protein in quantities sufficient for NMR spectroscopy. Close proximity of the TMS and tert-Bu groups was readily detected by nuclear Overhauser effects.

Journal of the American Chemical Society 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 C11H22N2O4, Related Products of amides-buliding-blocks.

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

Hu, Liming published the artcileThermophilic pyrrolysyl-tRNA synthetase mutants for enhanced mammalian genetic code expansion, Quality Control of 2418-95-3, the publication is ACS Synthetic Biology (2020), 9(10), 2723-2736, database is CAplus and MEDLINE.

Genetic code expansion (GCE) is a powerful technique for site-specific incorporation of noncanonical amino acids (ncAAs) into proteins in living cells, which is achieved through evolved aminoacyl-tRNA synthetase mutants. Stability is important for promoting enzyme evolution, and we found that many of the evolved synthetase mutants have reduced thermostabilities. In this study, we characterized two novel pyrrolysyl-tRNA synthetases (PylRSs) derived from thermophilic archaea: Methanosarcina thermophila (Mt) and Methanosarcina flavescens (Mf). Further study demonstrated that the wild-type PylRSs and several mutants were orthogonal and active in both Escherichia coli and mammalian cells and could thus be used for GCE. Compared with the commonly used M. barkeri PylRS, the wild-type thermophilic PylRSs displayed reduced GCE efficiency; however, some of the mutants, as well as some chimeras, outperformed their mesophilic counterparts in mammalian cell culture at 37°C. Their better performance could at least partially be attributed to the fact that these thermophilic synthetases exhibit a threshold of enhanced stability against destabilizing mutations to accommodate structurally diverse substrate analogs. These were indicated by the higher melting temperatures (by 3-6°C) and the higher expression levels that were typically observed for the MtPylRS and MfPylRS mutants relative to the Mb equivalent Using histone H3 as an example, we demonstrated that one of the thermophilic synthetase mutants promoted the incorporation of multiple acetyl-lysine residues in mammalian cells. The enzymes developed in this study add to the PylRS toolbox and provide potentially better scaffolds for PylRS engineering and evolution, which will be necessary to meet the increasing demands for expanded substrate repertoire with better efficiency and specificity in mammalian systems.

ACS Synthetic Biology 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 C11H22N2O4, Quality Control of 2418-95-3.

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

Fang, Danxuan published the artcileStable, Bioresponsive, and Macrophage-Evading Polyurethane Micelles Containing an Anionic Tripeptide Chain Extender, HPLC of Formula: 2418-95-3, the publication is ACS Omega (2019), 4(15), 16551-16563, database is CAplus and MEDLINE.

Polymeric nanocarriers have been extensively used in medicinal applications for drug delivery. However, i.v. nanocarriers circulating in the blood will be rapidly cleared from the mononuclear macrophage system. The surface physicochem. characterizations of nanocarriers are the primary factors to determine their fate in vivo, such as evading the reticuloendothelial system, exhibiting long blood circulation times, and accumulating in the targeted site. In this work, we develop a series of polyurethane micelles containing segments of an anionic tripeptide, hydrophilic mPEG, and disulfide bonds. It is found that the long hydrophilic mPEG can shield the micellar surface and have a synergistic effect with the neg. charged tripeptide to minimize macrophage phagocytosis. Meanwhile, the disulfide bond can rapidly respond to the intracellular reduction environment, leading to the acceleration of drug release and improvement of the therapeutic effect. Our results verify that these anionic polyurethane micelles hold great potential in the development of the stealth immune system and controllable intracellular drug transporters.

ACS Omega 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 C11H22N2O4, HPLC of Formula: 2418-95-3.

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

Huang, Sheng-Yin published the artcileA turn-on luminescent europium probe for cyanide detection in water, Category: amides-buliding-blocks, the publication is Chemical Communications (Cambridge, United Kingdom) (2018), 54(66), 9210-9213, database is CAplus and MEDLINE.

A luminescent europium probe that responds to cyanide directly in water with a large nine-fold turn-on of the Eu^III centered time-gated luminescence is presented. Unlike other CN^– probes reported, the mechanism of action of Eu^III-Lys-HOPO does not rely on reaction of CN^– with the probe, but on direct coordination of CN^– to the Eu^III ion concomitant with displacement of three inner-sphere water mols. This unusual coordination of CN^– with a lanthanide ion in aqueous solution was confirmed by luminescence lifetime measurements.

Chemical Communications (Cambridge, United Kingdom) 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 C11H22N2O4, Category: amides-buliding-blocks.

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

Monty, Olivier B. C. published the artcileHomogeneous and Functional Group Tolerant Ring-Closing Metathesis for DNA-Encoded Chemical Libraries, Related Products of amides-buliding-blocks, the publication is ACS Combinatorial Science (2020), 22(2), 80-88, database is CAplus and MEDLINE.

Reaction heterogeneity, poor pH control, and catalyst decomposition in the ring-closing metathesis (RCM) of DNA-chem. conjugates lead to poor yields of the cyclized products. Herein we address these issues with a RCM reaction system that includes a novel aqueous solvent combination to enable reaction homogeneity, an acidic buffer system which masks traditionally problematic functional groups, and a decomposition-resistant catalyst which maximizes conversion to the cyclized product. Addnl., we provide a systematic study of the substrate scope of the on-DNA RCM reaction, a demonstration of its applicability to a single-substrate DNA-encoded chem. library that includes sequencing anal., and the first successful stapling of an unprotected on-DNA [i, i+4] peptide.

ACS Combinatorial Science 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 C11H22N2O4, Related Products of amides-buliding-blocks.

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

McCutcheon, David C. published the artcilePhotoproximity Profiling of Protein-Protein Interactions in Cells, Recommanded Product: H-Lys(Boc)-OH, the publication is Journal of the American Chemical Society (2020), 142(1), 146-153, database is CAplus and MEDLINE.

We report a novel photoproximity protein interaction (PhotoPPI) profiling method to map protein-protein interactions in vitro and in live cells. This approach utilizes a bioorthogonal, multifunctional chem. probe that can be targeted to a genetically encoded protein of interest (POI) through a modular SNAP-Tag/benzylguanine covalent interaction. A first generation photoproximity probe, PP1, responds to 365 nm light to simultaneously cleave a central nitroveratryl linker and a peripheral diazirine group, resulting in diffusion of a highly reactive carbene nucleophile away from the POI. We demonstrate facile probe loading, and subsequent interaction- and light-dependent proximal labeling of a model protein-protein interaction (PPI) in vitro. Integration of the PhotoPPI workflow with quant. LC-MS/MS enabled unbiased interaction mapping for the redox regulated sensor protein, KEAP1, for the first time in live cells. We validated known and novel interactions between KEAP1 and the proteins PGAM5 and HK2, among others, under basal cellular conditions. By contrast, comparison of PhotoPPI profiles in cells experiencing metabolic or redox stress confirmed that KEAP1 sheds many basal interactions and becomes associated with known lysosomal trafficking and proteolytic proteins like SQSTM1, CTSD, and LGMN. Together, these data establish PhotoPPI as a method capable of tracking the dynamic subcellular and protein interaction “social network” of a redox-sensitive protein in cells with high temporal resolution

Journal of the American Chemical Society 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 C11H22N2O4, Recommanded Product: H-Lys(Boc)-OH.

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

Ko, Wooseok published the artcileConstruction of bacterial cells with an active transport system for unnatural amino acids, Application In Synthesis of 2418-95-3, the publication is ACS Synthetic Biology (2019), 8(5), 1195-1203, database is CAplus and MEDLINE.

Engineered organisms with an expanded genetic code have attracted much attention in chem. and synthetic biol. research. In this work, engineered bacterial organisms with enhanced unnatural amino acid (UAA) uptake abilities were developed by screening periplasmic binding protein (PBP) mutants for recognition of UAAs. A FRET-based assay was used to identify a mutant PBP (LBP-AEL) with excellent binding affinity (K_d ≈ 500 nM) to multiple UAAs from 37 mutants. Bacterial cells expressing LBP-AEL showed up to 5-fold enhanced uptake of UAAs, which was determined by genetic incorporation of UAAs into a green fluorescent protein and measuring UAA concentration in cell lysates. To the best of our knowledge, this work is the first report of engineering cellular uptake of UAAs and could provide an impetus for designing advanced unnatural organisms with an expanded genetic code, which function with the efficiency comparable to that of natural organisms. The system would be useful to increase mutant protein yield from lower concentrations of UAAs for industrial and large-scale applications. In addition, the techniques used in this report such as the sensor design and the measurement of UAA concentration in cell lysates could be useful for other biochem. applications.

ACS Synthetic Biology 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 C11H22N2O4, Application In Synthesis of 2418-95-3.

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

Stieglitz, Jessica T. published the artcileExploration of Methanomethylophilus alvus pyrrolysyl-tRNA synthetase activity in yeast, Category: amides-buliding-blocks, the publication is ACS Synthetic Biology (2022), 11(5), 1824-1834, database is CAplus and MEDLINE.

Archaeal pyrrolysyl-tRNA synthetases (PylRSs) have been used to genetically encode over 200 distinct noncanonical amino acids (ncAAs) in proteins in Escherichia coli and mammalian cells. This vastly expands the range of chem. functionality accessible within proteins produced in these organisms. Despite these clear successes, explorations of PylRS function in yeast remain limited. In this work, we demonstrate that the Methanomethylophilus alvus PylRS (MaPylRS) and its cognate tRNA_CUA^MaPyl support the incorporation of ncAAs into proteins produced in Saccharomyces cerevisiae using stop codon suppression methodologies. Addnl., we prepared three MaPylRS mutants originally engineered in E. coli and determined that all three were active with one or more ncAAs, although with low efficiencies of ncAA incorporation in comparison to the parent MaPylRS. Alongside MaPylRS variants, we evaluated the activity of previously reported Methanosarcina mazei, Methanosarcina barkeri, and chimeric M. mazei and M. barkeri PylRSs. Using S. cerevisiae RJY100 and pairing these PylRSs with the M. mazei tRNA_CUA, we did not observe any detectable stop codon suppression activity under the same conditions that produced moderately efficient ncAA incorporation with MaPylRS. The addition of MaPylRS/tRNA_CUA^MaPyl to the orthogonal translation machinery toolkit in S. cerevisiae potentially opens the door to hundreds of ncAAs that have not previously been genetically encodable using other aminoacyl-tRNA synthetase/tRNA pairs. Extending the scope of ncAA incorporation in yeast could powerfully advance chem. and biol. research for applications ranging from basic biol. discovery to enzyme engineering and therapeutic protein lead discovery.

ACS Synthetic Biology 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 C15H14O3, Category: amides-buliding-blocks.

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