Tag: M.W=400-450

Siow, Andrew published the artcileTotal synthesis of the highly N-methylated acetylene-containing anticancer peptide Jahanyne, Related Products of ethers-buliding-blocks, the publication is Organic Letters (2018), 20(3), 788-791, database is CAplus and MEDLINE.

The first total synthesis of the highly N-methylated acetylene-containing lipopeptide jahanyne, an apoptosis-inducing natural product from marine cyanobacteria, is reported. A late-stage solution-phase coupling enabled introduction of the C-terminal ketone pyrrolidine moiety. A modified Fmoc (Fmoc = 9-fluorenylmetoxycarbonyl) solid-phase synthesis strategy was adopted to effectively couple multiple sterically hindered N-methylated amino acids while suppressing epimerization. The total synthesis has enabled confirmation of the proposed absolute configuration of natural jahanyne.

Organic 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 C15H21BO3, Related Products of ethers-buliding-blocks.

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

Wang, Conan K. published the artcileExploring experimental and computational markers of cyclic peptides: Charting islands of permeability, Application of (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, the publication is European Journal of Medicinal Chemistry (2015), 202-213, database is CAplus and MEDLINE.

An increasing number of macrocyclic peptides that cross biol. membranes are being reported, suggesting that it might be possible to develop peptides into orally bioavailable therapeutics; however, current understanding of what makes macrocyclic peptides cell permeable is still limited. Here, we synthesized 62 cyclic hexapeptides and characterized their permeability using in vitro assays commonly used to predict in vivo absorption rates, i.e. the Caco-2 and PAMPA assays. We correlated permeability with exptl. measured parameters of peptide conformation obtained using rapid methods based on chromatog. and NMR spectroscopy. Based on these correlations, we propose a model describing the interplay between peptide permeability, lipophilicity and hydrogen bonding potential. Specifically, peptides with very high permeability have high lipophilicity and few solvent hydrogen bond interactions, whereas peptides with very low permeability have low lipophilicity or many solvent interactions. Our model is supported by mol. dynamics simulations of the cyclic peptides calculated in explicit solvent, providing a structural basis for the observed correlations. This prospective exploration into biomarkers of peptide permeability has the potential to unlock wider opportunities for development of peptides into drugs.

European 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 C12H13F2N3O4S, 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

Misu, Ryosuke published the artcileStructure-activity relationship study of tachykinin peptides for the development of novel neurokinin-3 receptor selective agonists, HPLC of Formula: 77128-73-5, the publication is Bioorganic & Medicinal Chemistry (2013), 21(8), 2413-2417, database is CAplus and MEDLINE.

Neurokinin B (NKB) is a potential regulator of pulsatile gonadotropin-releasing hormone (GnRH) secretion via activation of the neurokinin-3 receptor (NK3R). NKB with the consensus sequence of the tachykinin peptide family also binds to other tachykinin receptors [neurokinin-1 receptor (NK1R) and neurokinin-2 receptor (NK2R)] with low selectivity. In order to identify the structural requirements for the development of novel potent and selective NK3R agonists, a structure-activity relationship (SAR) study of [MePhe⁷]-NKB and other naturally occurring tachykinin peptides was performed. The substitutions to naturally occurring tachykinins with Asp and MePhe improved the receptor binding and agonistic activity for NK3R. The corresponding substitutions to NKB provided an NK3R selective analog.

Bioorganic & 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, HPLC of Formula: 77128-73-5.

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

Bai, Xiaohui published the artcileA new GLP-1 analogue with prolonged glucose-lowering activity in vivo via backbone-based modification at the N-terminus, Recommanded Product: (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, the publication is Bioorganic & Medicinal Chemistry (2016), 24(6), 1163-1170, database is CAplus and MEDLINE.

Glucagon-like peptide-1 (GLP-1) is an endogenous insulinotropic hormone with wonderful glucose-lowering activity. However, its clin. use in type II diabetes is limited due to its rapid degradation at the N-terminus by dipeptidyl peptidase IV (DPP-IV). Among the N-terminal modifications of GLP-1, backbone-based modification was rarely reported. Herein, the authors employed two backbone-based strategies to modify the N-terminus of tGLP-1. Firstly, the amide N-methylated analogs were designed and synthesized to make a full screening of the N-terminal amide bonds, and the loss of GLP-1 receptor (GLP-1R) activation indicated the importance of amide H-bonds. Secondly, with retaining the N-terminal amide H-bonds, the β-peptide replacement strategy was used and analogs were synthesized. By two rounds of screening, analog (I) was identified. Analog (I) greatly improved the DPP-IV resistance with maintaining good GLP-1R activation in vitro, and showed approx. a 4-fold prolonged blood glucose-lowering activity in vivo in comparison with tGLP-1. This modification strategy will benefit the development of GLP-1-based anti-diabetic drugs.

Bioorganic & 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, 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

Kurasaki, Haruaki published the artcileIsostearyl mixed anhydrides for the preparation of N-methylated peptides using C-terminally unprotected N-methylamino acids, Synthetic Route of 77128-73-5, the publication is Organic Letters (2020), 22(20), 8039-8043, database is CAplus and MEDLINE.

Sustainable and efficient manufacturing methods for N-methylated peptides remain underexplored despite growing interest in therapeutic N-methylated peptides within the pharmaceutical industry. A methodol. for the coupling of C-terminally unprotected N-methylamino acids mediated by an isostearic acid halide (ISTAX) and silylating reagent has been developed. This approach allows for the coupling of a wide variety of amino acids and peptides in high yields under mild conditions without the need for a C-terminal deprotection step in the process of C-terminal elongation. These advantages make this a useful synthetic method for the production of peptide therapeutics and diagnostics containing N-methylamino acids.

Organic 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, Synthetic Route of 77128-73-5.

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

Yeomans, Larisa published the artcilePhosphorylation of enkephalins: NMR and CD studies in aqueous and membrane-mimicking environments, Recommanded Product: (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, the publication is Chemical Biology & Drug Design (2011), 78(5), 749-756, database is CAplus and MEDLINE.

Phosphorylation of L-serine-containing enkephalin analogs has been explored as an alternative to glycosylation in an effort to increase blood-brain barrier permeability and CNS bioavailability of peptide pharmacophores. Two enkephalin-based peptides were modified for these studies, a set related to DTLES, a mixed μ/δ-agonist, and one related to DAMGO, a highly selective μ-agonist. Each unglycosylated peptide was compared to its phosphate, its mono-benzylphosphate ester, and its β-D-glucoside. Binding was characterized in membrane preparations from Chinese hamster ovary cells expressing human μ, δ and κ-opiate receptors. Antinociception was measured in mice using the 55 °C tail-flick assay. To estimate bioavailability, the antinociceptive effect of each opioid agonist was evaluated after intracerebroventricular (i.c.v.) or i.v. administration (i.v.) of the peptides. CD methods and high-field NMR were used in the presence and absence of sodium dodecylsulfate to understand how the presence of a membrane might influence the peptide conformations.

Chemical Biology & Drug Design 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 C7H6BF3O2S, 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

Stolze, Sara C. published the artcileDevelopment of a Solid-Phase Approach to the Natural Product Class of Ahp-Containing Cyclodepsipeptides, Safety of (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, the publication is European Journal of Organic Chemistry (2012), 2012(8), 1616-1625, S1616/1-S1616/32, database is CAplus.

The 3-amino-6-hydroxy-2-piperidone (Ahp) containing cyclodepsipeptides are an interesting class of natural products that inhibit S1 (trypsin and chymotrypsin-like) serine protease in a reversible, noncovalent manner, turning them into potential chem. tools for protease research. Their systematic use in chem. biol. is however hampered by their tedious solution-phase chem. synthesis. To overcome this limitation, the authors report a solid-phase approach to Ahp cyclodepsipeptides that is based on the use of a masked glutamic aldehyde moiety as a general Ahp precursor mol. As a proof-of-concept, the authors therefore recently reported the solid-phase synthesis of symplocamide A. Here, the authors want to give a full account on the development and application of the masked glutamic aldehyde moiety as well as the optimization of the solid-phase synthesis, which allowed the successful synthesis of the natural product symplocamide A.

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 C4Br2N2O4S, 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

Stolze, Sara C. published the artcileAhp Cyclodepsipeptides: The Impact of the Ahp Residue on the “Canonical Inhibition” of S1 Serine Proteases, Formula: C25H23NO4, the publication is ChemBioChem (2013), 14(11), 1301-1308, database is CAplus and MEDLINE.

S1 serine proteases are by far the largest and most diverse family of proteases encoded in the human genome. Although recent decades have seen an enormous increase in our knowledge, the biol. functions of most of these proteases remain to be elucidated. Chem. inhibitors have proven to be versatile tools for studying the functions of proteases, but this approach is hampered by the limited availability of inhibitor scaffold structures with the potential to allow rapid discovery of selective, noncovalent small-mol. protease inhibitors. The natural product class of Ahp cyclodepsipeptides is an unusual class of small-mol. canonical inhibitors; the incorporation of protease cleavage sequences into their mol. scaffolds enables the design of specific small-mol. inhibitors that simultaneously target the S and S’ subsites of the protease through noncovalent mechanisms. Their synthesis is tedious, however, so in this study we have investigated the relevance of the Ahp moiety for achieving potent inhibition. We found that although the Ahp residue plays an important role in inhibition potency, appropriate replacement with β-hydroxy amino acids results in structurally less complex derivatives that inhibit serine proteases in the low micromolar range.

ChemBioChem 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 C12H12F3N5O2, Formula: C25H23NO4.

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

Chiba, Takuya published the artcileStructure-activity relationship study of syringolin A as a potential anticancer agent, HPLC of Formula: 77128-73-5, the publication is Bioorganic & Medicinal Chemistry Letters (2015), 25(21), 4872-4877, database is CAplus and MEDLINE.

A detailed structure-activity relationship of syringolin, which is a promising antitumor natural product, was described. The authors previously developed syringolin A analog I as a potent proteasome inhibitor by the structure-based drug design of syringolin A. The authors synthesized a range of analogs of I, having a different length of the lipophilic chain and substituted aryl group, and their cytotoxicity against human cancer cells was evaluated. It turned out that these modifications greatly affected the cytotoxicity. Further optimization would lead to develop a novel proteasome inhibitor.

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, HPLC of Formula: 77128-73-5.

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

Anokhina, Viktoriya S. published the artcileEnhancing the ligand efficiency of anti-HIV compounds targeting frameshift-stimulating RNA, Category: ethers-buliding-blocks, the publication is Bioorganic & Medicinal Chemistry (2019), 27(13), 2972-2977, database is CAplus and MEDLINE.

Ribosomal frameshifting, a process whereby a translating ribosome is diverted from one reading frame to another on a contiguous mRNA, is an important regulatory mechanism in biol. and an opportunity for therapeutic intervention in several human diseases. In HIV, ribosomal frameshifting controls the ratio of Gag and Gag-Pol, two polyproteins critical to the HIV life cycle. We have previously reported compounds able to selectively bind an RNA stemloop within the Gag-Pol mRNA; these compounds alter the production of Gag-Pol in a manner consistent with increased frameshifting. Importantly, they also display antiretroviral activity in human T-cells. Here, we describe new compounds with significantly reduced mol. weight, but with substantially maintained affinity and anti-HIV activity. These results suggest that development of more “ligand efficient” enhancers of ribosomal frameshifting is an achievable goal.

Bioorganic & 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, Category: ethers-buliding-blocks.

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