Tag: M.W=400-450

Fernandez-Llamazares, Ana I. published the artcileN-Triethylene glycol (N-TEG) as a surrogate for the N-methyl group: application to Sansalvamide A peptide analogs, Recommanded Product: (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, the publication is Chemical Communications (Cambridge, United Kingdom) (2013), 49(57), 6430-6432, database is CAplus and MEDLINE.

The authors have studied the N-triethylene glycol (N-TEG) group as a surrogate for the N-Me group in Sansalvamide A peptide. The five N-TEG and N-Me analogs of this cyclic pentapeptide were synthesized, and their biol. activity, lipophilicity and conformational features were compared.

Chemical Communications (Cambridge, United Kingdom) published new progress about 77128-73-5. 77128-73-5 belongs to ethers-buliding-blocks, auxiliary class Inhibitor, name is (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, and the molecular formula is C25H23NO4, Recommanded Product: (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid.

Referemce:
https://en.wikipedia.org/wiki/Ether,
Ether | (C2H5)2O – PubChem

Juhl, Cathleen published the artcileDevelopment of Potent and Metabolically Stable APJ Ligands with High Therapeutic Potential, Related Products of ethers-buliding-blocks, the publication is ChemMedChem (2016), 11(21), 2378-2384, database is CAplus and MEDLINE.

The apelin ligand receptor system is an important target to develop treatment strategies for cardiovascular diseases. Although apelin exhibits strong inotropic effects, its pharmaceutical application is limited because no agonist with suitable properties is available. On the one hand, peptide ligands are too instable, and on the other hand, small-mol. agonists show only low potency. This study describes the development of apelin (APJ) receptor agonists with not only high activity but also metabolic stability. Several strategies including capping of termini, insertion of unnatural amino acids, cyclization, and lipidation were analyzed. Peptide activity was tested using a Ca²⁺-mobilization assay and the degradation of selected analogs was analyzed in rat plasma. The best results were obtained by N-terminal lipidation of a 13-mer apelin derivative This analog displayed a half-life of 29 h in rat plasma, compared with 0.025 h for the wild-type peptide. Furthermore, in vivo pharmacokinetics revealed a clearance of 0.049 L h^-1 kg^-1 and a half-life of 0.36 h. In summary, amino acid substitution and fatty acid modification resulted in a potent and 1000-fold more stable peptide that exhibits high pharmaceutical potential.

ChemMedChem published new progress about 77128-73-5. 77128-73-5 belongs to ethers-buliding-blocks, auxiliary class Inhibitor, name is (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, and the molecular formula is C25H23NO4, Related Products of ethers-buliding-blocks.

Referemce:
https://en.wikipedia.org/wiki/Ether,
Ether | (C2H5)2O – PubChem

Pham, Johnny D. published the artcilePolymorphism of Oligomers of a Peptide from β-Amyloid, Safety of (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, the publication is Journal of the American Chemical Society (2014), 136(14), 5432-5442, database is CAplus and MEDLINE.

This contribution reports solution-phase structural studies of oligomers of a family of peptides derived from the β-amyloid peptide (Aβ). We had previously reported the x-ray crystallog. structures of the oligomers and oligomer assemblies formed in the solid state by a macrocyclic β-sheet peptide containing the Aβ_15-23 nonapeptide. In the current study, we set out to determine its assembly in aqueous solution In the solid state, macrocyclic β-sheet peptide 1 assembles to form hydrogen-bonded dimers that further assemble in a sandwich-like fashion to form tetramers through hydrophobic interactions between the faces bearing V₁₈ and F₂₀. In aqueous solution, macrocyclic β-sheet peptide 1 and homolog 2a form hydrogen-bonded dimers that assemble to form tetramers through hydrophobic interactions between the faces bearing L₁₇, F₁₉, and A₂₁. In the solid state, the hydrogen-bonded dimers are antiparallel, and the β-strands are fully aligned, with residues 17-23 of one of the macrocycles aligned with residues 23-17 of the other. In solution, residues 17-23 of the hydrogen-bonded dimers are shifted out of alignment by two residues toward the C-termini. The two hydrogen-bonded dimers are nearly orthogonal in the solid state, while in solution the dimers are only slightly rotated. The differing morphol. of the solution-state and solid-state tetramers is significant, because it may provide a glimpse into some of the structural bases for polymorphism among Aβ oligomers in Alzheimer’s disease.

Journal of the American Chemical Society published new progress about 77128-73-5. 77128-73-5 belongs to ethers-buliding-blocks, auxiliary class Inhibitor, name is (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, and the molecular formula is C25H23NO4, Safety of (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid.

Referemce:
https://en.wikipedia.org/wiki/Ether,
Ether | (C2H5)2O – PubChem

Zhang, Shengping published the artcileCyclization of linear tetrapeptides containing N-methylated amino acids by using 1-propanephosphonic acid anhydride, SDS of cas: 77128-73-5, the publication is European Journal of Organic Chemistry (2017), 2017(1), 149-158, database is CAplus.

The cyclization of the linear tetrapeptides sequence H-NMePhe-Xaa¹-NMePhe-Xaa²-OH (for which Xaa¹ = Xaa² = Ile, Val, or Leu; Xaa¹ = Val; Xaa² = Ile or Leu) by using 1-propanephosphonic acid anhydride was explored. An unanticipated finding is the cyclization towards cyclotetrapeptide conformers (kinetic products) that were highly prone to hydrolysis and that slowly interconvert into the more stable trans,cis,trans,cis (tctc) conformers (thermodn. products).

European Journal of Organic Chemistry published new progress about 77128-73-5. 77128-73-5 belongs to ethers-buliding-blocks, auxiliary class Inhibitor, name is (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, and the molecular formula is C6H12F3NO5S, SDS of cas: 77128-73-5.

Referemce:
https://en.wikipedia.org/wiki/Ether,
Ether | (C2H5)2O – PubChem

Premnath, Padmavathy Nandha published the artcileBenzamide capped peptidomimetics as non-ATP competitive inhibitors of CDK2 using the REPLACE strategy, Product Details of C25H23NO4, the publication is Bioorganic & Medicinal Chemistry Letters (2016), 26(15), 3754-3760, database is CAplus and MEDLINE.

Inhibition of cyclin dependent kinase 2 (CDK2) in complex with cyclin A in G1/S phase of the cell cycle has been shown to promote selective apoptosis of cancer cells through the E2F1 pathway. An alternative approach to catalytic inhibition is to target the substrate recruitment site also known as the cyclin binding groove (CBG) to generate selective non-ATP competitive inhibitors. The REPLACE strategy has been applied to identify fragment alternatives and substituted benzoic acid derivatives were evaluated as a promising scaffold to present appropriate functionality to mimic key peptide determinants. Fragment Ligated Inhibitory Peptides (FLIPs) are described which potently inhibit both CDK2/cyclin A and CDK4/cyclin D1 and have preliminary antitumor activity. A structural rationale for binding was obtained through mol. modeling further demonstrating their potential for further development as next generation non ATP competitive CDK inhibitors.

Bioorganic & Medicinal Chemistry Letters published new progress about 77128-73-5. 77128-73-5 belongs to ethers-buliding-blocks, auxiliary class Inhibitor, name is (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, and the molecular formula is C25H23NO4, Product Details of C25H23NO4.

Referemce:
https://en.wikipedia.org/wiki/Ether,
Ether | (C2H5)2O – PubChem

Brousseau, Margaret E. published the artcileIdentification of a PCSK9-LDLR disruptor peptide with in vivo function, COA of Formula: C25H23NO4, the publication is Cell Chemical Biology (2022), 29(2), 249-258.e5, database is CAplus and MEDLINE.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates plasma low-d. lipoprotein cholesterol (LDL-C) levels by promoting hepatic LDL receptor (LDLR) degradation Therapeutic antibodies that disrupt PCSK9-LDLR binding reduce LDL-C concentrations and cardiovascular disease risk. The epidermal growth factor precursor homol. domain A (EGF-A) of the LDLR serves as a primary contact with PCSK9 via a flat interface, presenting a challenge for identifying small mol. PCSK9-LDLR disruptors. We employ an affinity-based screen of 1013in vitro-translated macrocyclic peptides to identify high-affinity PCSK9 ligands that utilize a unique, induced-fit pocket and partially disrupt the PCSK9-LDLR interaction. Structure-based design led to mols. with enhanced function and pharmacokinetic properties (e.g., ₁₃PCSK9i). In mice, ₁₃PCSK9i reduces plasma cholesterol levels and increases hepatic LDLR d. in a dose-dependent manner. ₁₃PCSK9i functions by a unique, allosteric mechanism and is the smallest mol. identified to date with in vivo PCSK9-LDLR disruptor function.

Cell Chemical Biology published new progress about 77128-73-5. 77128-73-5 belongs to ethers-buliding-blocks, auxiliary class Inhibitor, name is (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, and the molecular formula is C25H23NO4, COA of Formula: C25H23NO4.

Referemce:
https://en.wikipedia.org/wiki/Ether,
Ether | (C2H5)2O – PubChem

Premnath, Padmavathy Nandha published the artcileIterative Conversion of Cyclin Binding Groove Peptides into Druglike CDK Inhibitors with Antitumor Activity, SDS of cas: 77128-73-5, the publication is Journal of Medicinal Chemistry (2015), 58(1), 433-442, database is CAplus and MEDLINE.

The cyclin groove is an important recognition site for substrates of the cell cycle cyclin-dependent kinases and provides an opportunity for highly selective inhibition of kinase activity through a non-ATP competitive mechanism. The key peptide residues of the cyclin binding motif have been studied in order to precisely define the structure-activity relationship for CDK kinase inhibition. Through this information, new insights into the interactions of peptide CDK inhibitors with key subsites of the cyclin binding groove provide for the replacement of binding determinants with more druglike functionality through REPLACE, a strategy for the iterative conversion of peptidic blockers of protein-protein interactions into pharmaceutically relevant compounds As a result, REPLACE is further exemplified in combining optimized peptidic sequences with effective N-terminal capping groups to generate more stable compounds possessing antitumor activity consistent with on-target inhibition of cell cycle CDKs. The compounds described here represent prototypes for a next generation of kinase therapeutics with high efficacy and kinome selectivity, thus avoiding problems observed with first generation CDK inhibitors.

Journal of Medicinal Chemistry published new progress about 77128-73-5. 77128-73-5 belongs to ethers-buliding-blocks, auxiliary class Inhibitor, name is (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, and the molecular formula is C25H23NO4, SDS of cas: 77128-73-5.

Referemce:
https://en.wikipedia.org/wiki/Ether,
Ether | (C2H5)2O – PubChem

Kheirabadi, Mahboubeh published the artcileLeveraging a “Catch-Release” Logic Gate Process for the Synthesis and Nonchromatographic Purification of Thioether- or Amine-Bridged Macrocyclic Peptides, Product Details of C25H23NO4, the publication is Journal of Organic Chemistry (2018), 83(8), 4323-4335, database is CAplus and MEDLINE.

Macrocyclic peptides containing N-alkylated amino acids have emerged as a promising therapeutic modality, capable of modulating protein-protein interactions and an intracellular delivery of hydrophilic payloads. While multichannel automated solid-phase peptide synthesis (SPPS) is a practical approach for peptide synthesis, the requirement for slow and inefficient chromatog. purification of the product peptides is a significant limitation to exploring these novel compounds Herein, we invent a “catch-release” strategy for the nonchromatog. purification of macrocyclic peptides. A traceless catch process is enabled by the invention of a dual-functionalized N-terminal acetate analog, which serves as a handle for capture onto a purification resin and as a leaving group for macrocyclization. Displacement by a C-terminal nucleophilic side chain thus releases the desired macrocycle from the purification resin. By design, this catch/release process is a logic test for the presence of the key components required for cyclization, thus removing impurities which lack the required functionality, such as common classes of peptide impurities, including hydrolysis fragments and truncated sequences. The method was shown to be highly effective with three libraries of macrocyclic peptides, containing macrocycles of 5-20 amino acids, with either thioether- or amine-based macrocyclic linkages; in this latter class, the reported method represents an enabling technol. In all cases, the catch-release protocol afforded significant enrichment of the target peptides purity, in many cases completely obviating the need for chromatog. Importantly, we have adapted this process for automation on a standard multichannel peptide synthesizer, achieving an efficient and completely integrated synthesis and purification platform for the preparation of these important mols.

Journal of Organic Chemistry published new progress about 77128-73-5. 77128-73-5 belongs to ethers-buliding-blocks, auxiliary class Inhibitor, name is (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, and the molecular formula is C25H23NO4, Product Details of C25H23NO4.

Referemce:
https://en.wikipedia.org/wiki/Ether,
Ether | (C2H5)2O – PubChem

Sethi, Dalip published the artcileFluorescent Peptide-PNA Chimeras for Imaging Monoamine Oxidase A mRNA in Neuronal Cells, Product Details of C25H23NO4, the publication is Bioconjugate Chemistry (2012), 23(2), 158-163, database is CAplus and MEDLINE.

Monoamine oxidases (MAO) catalyze the oxidative deamination of many biogenic amines and are integral proteins found in the mitochondrial outer membrane. Changes in MAO-A levels are associated with depression, trait aggression, and addiction. Here we report the synthesis, characterization, and in vitro evaluation of novel fluorescent peptide-peptide nucleic acid (PNA) chimeras for MAOA mRNA imaging in live neuronal cells. The probes were designed to include MAOA-specific PNA dodecamers, separated by an N-terminal spacer to a μ-opioid receptor targeting peptide (DAMGO), with a spacer and a fluorophore on the C-terminus. The probe was successfully delivered into human SH-SY5Y neuroblastoma cells through μ-opioid receptor-mediated endocytosis. The K_d by flow cytometry was 11.6±0.8 nM. Uptake studies by fluorescence microscopy showed ∼5-fold higher signal in human SH-SY5Y neuroblastoma cells than in neg. control CHO-K1 cells that lack μ-opioid receptors. Moreover, a peptide-mismatch control sequence showed no significant uptake in SH-SY5Y cells. Such mRNA imaging agents with near-IR fluorophores might enable real time imaging and quantitation of neuronal mRNAs in live animal models.

Bioconjugate Chemistry published new progress about 77128-73-5. 77128-73-5 belongs to ethers-buliding-blocks, auxiliary class Inhibitor, name is (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, and the molecular formula is C4H6F3NOS, Product Details of C25H23NO4.

Referemce:
https://en.wikipedia.org/wiki/Ether,
Ether | (C2H5)2O – PubChem

Maharani, Rani published the artcileA total synthesis of a highly N-methylated cyclodepsipeptide [2S,3S-Hmp]-aureobasidin L using solid-phase methods, Computed Properties of 77128-73-5, the publication is Tetrahedron (2014), 70(14), 2351-2358, database is CAplus.

[2S,3S-Hmp]-Aureobasidin L 2 has been successfully synthesized through a combination of solution- and solid-phase peptide synthesis. All of the Fmoc-protected residues including a depsidipeptide, Fmoc-MeVal-Hmp-OH, were prepared in solution phase. Chain elongation on chlorotrityl resin was undertaken using selected coupling reagents including HBTU/HOBt, HATU/HOAt and BTC/collidine. Cleavage of the linear depsinonapeptide was followed by cyclization to give the desired cyclodepsipeptide.

Tetrahedron published new progress about 77128-73-5. 77128-73-5 belongs to ethers-buliding-blocks, auxiliary class Inhibitor, name is (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, and the molecular formula is C25H23NO4, Computed Properties of 77128-73-5.

Referemce:
https://en.wikipedia.org/wiki/Ether,
Ether | (C2H5)2O – PubChem