Tag: M.W=400-450

Adamska-Bartlomiejczyk, Anna published the artcileCyclic mu-opioid receptor ligands containing multiple N-methylated amino acid residues, Safety of (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, the publication is Bioorganic & Medicinal Chemistry Letters (2017), 27(8), 1644-1648, database is CAplus and MEDLINE.

In this study we report the in vitro activities of four cyclic opioid peptides with various sequence length/macrocycle size and N-methylamino acid residue content. N-Methylated amino acids were incorporated and cyclization was employed to enhance conformational rigidity to various extent. The effect of such modifications on ligand structure and binding properties were studied. The pentapeptide containing one endocyclic and one exocyclic N-methylated amino acid displayed the highest affinity to the μ-opioid receptor. This peptide was also shown to be a full agonist, while the other analogs failed to activate the μ-opioid receptor. Results of mol. docking studies provided rationale for the explanation of binding properties on a structural basis.

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, 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

Yoshida, Masahito published the artcileSolid-phase combinatorial synthesis and biological evaluation of destruxin E analogs, Recommanded Product: (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, the publication is Chemistry – A European Journal (2015), 21(50), 18417-18430, database is CAplus and MEDLINE.

The solid-phase combinatorial synthesis of cyclodepsipeptide destruxin E has been demonstrated. The combinatorial synthesis of cyclization precursors was achieved by using a split and pool method on SynPhase Lanterns. The products were successfully macrolactonized in parallel in the solution phase by using 2-methyl-6-nitrobenzoic anhydride and 4-(dimethylamino)pyridine N-oxide to afford macrolactones, and the subsequent formation of an epoxide in the side chain gave 18 member destruxin E analogs. Biol. evaluation of the analogs indicated that the N-MeAla residue was crucial to the induction of morphol. changes in osteoclast-like multinuclear cells (OCLs). Based on structure-activity relationships, azido-containing analogs (I) [R¹ = Me, R² = (CH₂)₄N₃, R³ = CH((S)-Me)CH₂Me; R¹ = Me, R² = iso-Pr, R³ = (CH₂)₄N₃; R¹ = (CH₂)₄N₃, R² = iso-Pr, R³ = CH((S)-Me)CH₂Me] were then designed for use as a mol. probe. The synthesis and biol. evaluation of analogs I revealed that I [R¹ = Me, R² = iso-Pr, R³ = (CH₂)₄N₃], in which the Ile residue was replaced with a Lys(N₃) residue, induced morphol. changes in OCLs at a sufficient concentration, and modification around the Ile residue would be tolerated for attachment of a chem. tag toward the target identification of destruxin E.

Chemistry – A European Journal 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 C17H37NO3, 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

Kaneda, Masato published the artcileTotal synthesis and stereochemical revision of stereocalpin A: Mirror-image approach for stereochemical assignments of the peptide-polyketide macrocycle, Category: ethers-buliding-blocks, the publication is Journal of Organic Chemistry (2018), 83(6), 3047-3060, database is CAplus and MEDLINE.

Stereocalpin A is a cyclic depsipeptide with cytotoxic activity isolated from the Antarctic lichen Stereocaulon alpinum. Although a number of synthetic investigations of the unprecedented 12-membered macrocycle of stereocalpin A with a dipeptide segment and a polyketide substructure have been conducted, the configurational assignment has not been completed. In this study, we achieved the first total synthesis and stereochem. revision of stereocalpin A. To facilitate the comprehensive assessment of eight possible stereocalpin A isomers, four stereoisomers of polyketide precursors were conjugated with L-Phe-L-MePhe and D-Phe-D-MePhe dipeptides (MePhe: N-methylphenylalanine) to provide four possible isomers and four mirror-image structures of the remaining isomers, resp. The comparative NMR anal. of a series of stereoisomers revealed that stereocalpin A possesses 2R,4S,5R-configurations, which is unique among the related 12-membered hybrid peptide-polyketide natural products reported recently. The NOE correlations in the polyketide substructure of stereocalpin A were also retrospectively analyzed among the eight possible stereoisomers.

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, Category: ethers-buliding-blocks.

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

Guo, Zufeng published the artcileRapamycin-inspired macrocycles with new target specificity, Recommanded Product: (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, the publication is Nature Chemistry (2019), 11(3), 254-263, database is CAplus and MEDLINE.

Rapamycin and FK506 are macrocyclic natural products with an extraordinary mode of action, in which they form binary complexes with FK506-binding protein (FKBP) through a shared FKBP-binding domain before forming ternary complexes with their resp. targets, mechanistic target of rapamycin (mTOR) and calcineurin, resp. Inspired by this, we sought to build a rapamycin-like macromol. library to target new cellular proteins by replacing the effector domain of rapamycin with a combinatorial library of oligopeptides. We developed a robust macrocyclization method using ring-closing metathesis and synthesized a 45,000-compound library of hybrid macrocycles (named rapafucins) using optimized FKBP-binding domains. Screening of the rapafucin library in human cells led to the discovery of rapadocin, an inhibitor of nucleoside uptake. Rapadocin is a potent, isoform-specific and FKBP-dependent inhibitor of the equilibrative nucleoside transporter 1 and is efficacious in an animal model of kidney ischemia reperfusion injury. Together, these results demonstrate that rapafucins are a new class of chem. probes and drug leads that can expand the repertoire of protein targets well beyond mTOR and calcineurin.

Nature 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, 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

Hawkins, Paige M. E. published the artcilePotent bactericidal antimycobacterials targeting the chaperone ClpC1 based on the depsipeptide natural products Ecumicin and Ohmyungsamycin A, SDS of cas: 77128-73-5, the publication is Journal of Medicinal Chemistry (2022), 65(6), 4893-4908, database is CAplus and MEDLINE.

Ohmyungsamycin A and ecumicin are structurally related cyclic depsipeptide natural products that possess activity against Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB). Herein, we describe the design and synthesis of a library of analogs of these two natural products using an efficient solid-phase synthesis and late-stage macrolactamization strategy. Lead analogs possessed potent activity against Mtb in vitro (min. inhibitory concentration 125-500 nM) and were shown to inhibit protein degradation by the mycobacterial ClpC1-ClpP1P2 protease with an associated enhancement of ClpC1 ATPase activity. The most promising analog from the series exhibited rapid bactericidal killing activity against Mtb, capable of sterilizing cultures after 7 days, and retained bactericidal activity against hypoxic non-replicating Mtb. This natural product analog was also active in an in vivo zebrafish model of infection.

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

Nielsen, Daniel S. published the artcileImproving on Nature: Making a Cyclic Heptapeptide Orally Bioavailable, Recommanded Product: (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, the publication is Angewandte Chemie, International Edition (2014), 53(45), 12059-12063, database is CAplus and MEDLINE.

The use of peptides in medicine is limited by low membrane permeability, metabolic instability, high clearance, and negligible oral bioavailability. The prediction of oral bioavailability of drugs relies on physicochem. properties that favor passive permeability and oxidative metabolic stability, but these may not be useful for peptides. Here we investigate effects of heterocyclic constraints, intramol. hydrogen bonds, and side chains on the oral bioavailability of cyclic heptapeptides. NMR-derived structures, amide H-D exchange rates, and temperature-dependent chem. shifts showed that the combination of rigidification, stronger hydrogen bonds, and solvent shielding by branched side chains enhances the oral bioavailability of cyclic heptapeptides in rats without the need for N-methylation.

Angewandte Chemie, International Edition 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

Pye, Cameron R. published the artcileNonclassical Size Dependence of Permeation Defines Bounds for Passive Adsorption of Large Drug Molecules, Safety of (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, the publication is Journal of Medicinal Chemistry (2017), 60(5), 1665-1672, database is CAplus and MEDLINE.

There is a growing number of intracellular protein-protein interactions (PPI’s) with potential therapeutic importance that demand larger ligands than those that neatly fit into most common criteria for “drug-likeness”. Macrocyclic peptides pro-vide the large surface area required to inhibit PPIs and, in principle, avoid many of the pitfalls associated with peptides, including low stability and membrane permeability. However, the design of passively cell-permeable mols. in this space remains a great challenge due to the poorly understood roles of mol. size and lipophilicity in determining passive membrane permeability above MW âˆ?00. Using split-pool combinatorial synthesis, we constructed a library of cyclic, per-N-methlyated peptides spanning a wide range of calculated lipohilicities (0 < AlogP < 8) and mol. weights (âˆ?00 Da < MW < âˆ?200 Da). Assaying mixtures of compounds using the Parallel Artificial Membrane Assay (PAMPA) revealed a steep drop-off in apparent passive permeability with increasing size and a bilinear relationship with lipophilicity. We observed a size dependence of permeability that is in stark disagreement with current permeation models. The lipophilicities required to overcome this size penalty led to poor aqueous solubility, effectively bounding the chem. space of likely passively permeable mols. This understanding provides a new set of design criteria for achieving permeability in larger mol. size regimes and suggests an operational cut-off beyond which passive permeability is constrained by a sharply increasing penalty on permeation through the system.

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, 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

Salveson, Patrick J. published the artcileControlling the Oligomerization State of Aβ-Derived Peptides with Light, Quality Control of 77128-73-5, the publication is Journal of the American Chemical Society (2018), 140(17), 5842-5852, database is CAplus and MEDLINE.

A key challenge in studying the biol. and biophys. properties of amyloid-forming peptides is that they assemble to form heterogeneous mixtures of soluble oligomers and insoluble fibrils. Photolabile protecting groups have emerged as tools to control the properties of biomols. with light. Blocking intermol. hydrogen bonds that stabilize amyloid oligomers provides a general strategy to control the biol. and biophys. properties of amyloid-forming peptides. In this paper we describe the design, synthesis, and characterization of macrocyclic β-hairpin peptides that are derived from amyloidogenic peptides and contain the N-2-nitrobenzyl photolabile protecting group. Each peptide contains two heptapeptide segments from Aβ_16-36 or Aβ_17-36 constrained into β-hairpins. The N-2-nitrobenzyl group is appended to the amide backbone of Gly₃₃ to disrupt the oligomerization of the peptides by disrupting intermol. hydrogen bonds. X-ray crystallog. reveals that N-2-nitrobenzyl groups can either block assembly into discrete oligomers or permit formation of trimers, hexamers, and dodecamers. Photolysis of the N-2-nitrobenzyl groups with long-wave UV light unmasks the amide backbone and alters the assembly and the biol. properties of the macrocyclic β-hairpin peptides. SDS-PAGE studies show that removing the N-2-nitrobenzyl groups alters the assembly of the peptides. MTT conversion and LDH release assays show that decaging the peptides induces cytotoxicity. CD studies and dye leakage assays with liposomes reveal that decaging modulates interactions of the peptides with lipid bilayers. Collectively, these studies demonstrate that incorporating N-2-nitrobenzyl groups into macrocyclic β-hairpin peptides provides a new strategy to probe the structures and the biol. properties of amyloid oligomers.

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, Quality Control of 77128-73-5.

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

Howitz, William J. published the artcileMacrocyclic Peptides Derived from Familial Alzheimer’s Disease Mutants Show Charge-Dependent Oligomeric Assembly and Toxicity, Synthetic Route of 77128-73-5, the publication is ACS Chemical Neuroscience (2022), 13(6), 714-720, database is CAplus and MEDLINE.

This work probes the role of charge in the oligomeric assembly, toxicity, and membrane destabilization of a series of peptides derived from Aβ and the E22Q and E22K familial mutants. In the mutant Aβ peptides, an acidic residue (E) is replaced with either a neutral or basic residue (Q or K), thus altering the net charge of the peptide. Acetylation at peripheral positions permits modulation of charge of the peptides and allows investigation of the role of charge in their oligomeric assembly, cytotoxicity, and membrane disruption. Peptides with the same net charge generally behave similarly even if the amino acid residue at position 22 differs. As the net charge of the peptide decreases, so does the extent of assembly, cytotoxicity, and membrane destabilization, which were determined using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, lactate dehydrogenase (LDH)-release assays with SH-SY5Y cells, and dye leakage assays using liposomes. These findings suggest that the charge of the amino acid side chain, rather than its size or hydrophobicity, accounts for the differences in the oligomeric assembly and toxicity of the E22 familial mutants of Aβ.

ACS Chemical Neuroscience 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, Synthetic Route of 77128-73-5.

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

Vezina-Dawod, Simon published the artcileConvenient two-step synthesis of highly functionalized benzo-fused 1,4-diazepin-3-ones and 1,5-diazocin-4-ones by sequential Ugi and intramolecular S_NAr reactions, Application of (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, the publication is Tetrahedron (2017), 73(44), 6347-6355, database is CAplus.

A rapid and efficient two-step method was reported for synthesis of polysubstituted 1,4-benzodiazepin-3-ones I [R¹ = t-Bu, (CH₂)₅, cyclohexyl, Bn; R² = (CH₂)₃, Bn, Ph, etc.; R³ = H, Me, Bn, etc.; R⁴ = H, Me] and 1,5-benzodiazocin-4-ones II in high yields [R⁵ = H, Ph, 3-methyl-1H-indolyl] using a multicomponent condensation/cyclization. This approach used an Ugi four-component reaction to condense readily available N-Fmoc-amino acids, amines and isocyanides with a 2-fluoro-5-nitrobenzaldehyde to afford Fmoc-protected bis-amide intermediates, e.g., III followed by a one-pot Fmoc-group removal, intramol. aromatic nucleophilic substitution for ring closure and side chain deprotection.

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 C12H16BNO4, Application 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