Tag: M.W=400-450

Magiera-Mularz, Katarzyna published the artcileBioactive Macrocyclic Inhibitors of the PD-1/PD-L1 Immune Checkpoint, Application of (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, the publication is Angewandte Chemie, International Edition (2017), 56(44), 13732-13735, database is CAplus and MEDLINE.

Blockade of the immunoinhibitory PD-1/PD-L1 pathway using monoclonal antibodies has shown impressive results with durable clin. antitumor responses. Anti-PD-1 and anti-PD-L1 antibodies have now been approved for the treatment of a number of tumor types, whereas the development of small mols. targeting immune checkpoints lags far behind. We characterized two classes of macrocyclic-peptide inhibitors directed at the PD-1/PD-L1 pathway. We show that these macrocyclic compounds act by directly binding to PD-L1 and that they are capable of antagonizing PD-L1 signaling and, similarly to antibodies, can restore the function of T-cells. We also provide the crystal structures of two of these small-mol. inhibitors bound to PD-L1. The structures provide a rationale for the checkpoint inhibition by these small mols., and a description of their small mol./PD-L1 interfaces provides a blueprint for the design of small-mol. inhibitors of the PD-1/PD-L1 pathway.

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, 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

Yamagishi, Yusuke published the artcileNatural Product-Like Macrocyclic N-Methyl-Peptide Inhibitors against a Ubiquitin Ligase Uncovered from a Ribosome-Expressed De Novo Library, Recommanded Product: (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, the publication is Chemistry & Biology (Cambridge, MA, United States) (2011), 18(12), 1562-1570, database is CAplus and MEDLINE.

Summary: Naturally occurring peptides often possess macrocyclic and N-methylated backbone. These features grant them structural rigidity, high affinity to targets, proteolytic resistance, and occasionally membrane permeability. Because such peptides are produced by either nonribosomal peptide synthetases or enzymic posttranslational modifications, it is yet a formidable challenge in degenerating sequence or length and preparing libraries for screening bioactive mols. Here, we report a new means of synthesizing a de novo library of “natural product-like” macrocyclic N-methyl-peptides using translation machinery under the reprogrammed genetic code, which is coupled with an in vitro display technique, referred to as RaPID (random nonstandard peptides integrated discovery) system. This system allows for rapid selection of strong binders against an arbitrarily chosen therapeutic target. Here, we have demonstrated the selection of anti-E6AP macrocyclic N-methyl-peptides, one of which strongly inhibits polyubiquitination of proteins such as p53.

Chemistry & Biology (Cambridge, MA, United States) 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 C3H5BN2O2, 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

Otake, Yuma published the artcileN-methylated peptide synthesis via generation of an acyl N-methylimidazolium cation accelerated by a Broensted acid, Category: ethers-buliding-blocks, the publication is Angewandte Chemie, International Edition (2020), 59(31), 12925-12930, database is CAplus and MEDLINE.

The development of a robust amide-bond formation remains a critical aspect of N-methylated peptide synthesis. In this study, we synthesized a variety of dipeptides in high yields, without severe racemization, from equivalent amounts of amino acids. Highly reactive N-methylimidazolium cation species were generated in situ to accelerate the amidation. The key to success was the addition of a strong Broensted acid. The developed amidation enabled the synthesis of a bulky peptide with a higher yield in a shorter amount of time compared with the results of conventional amidation. In addition, the amidation can be performed by using either a microflow reactor or a conventional flask. The first total synthesis of naturally occurring bulky N-methylated peptides, pterulamides I-IV, was achieved. Based on exptl. results and theor. calculations, we speculated that a Broensted acid would accelerate the rate-limiting generation of acyl imidazolium cations from mixed carbonic anhydrides.

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, Category: ethers-buliding-blocks.

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

Kapadia, Akshay published the artcileStructural and mechanistic insights into the inhibition of amyloid-β aggregation by Aβ_39-42 fragment derived synthetic peptides, Safety of (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, the publication is European Journal of Medicinal Chemistry (2021), 113126, database is CAplus and MEDLINE.

The inhibition of amyloid-β (Aβ) aggregation is a promising approach towards therapeutic intervention for Alzheimers disease (AD). Thirty eight tetrapeptides based upon Aβ39-42C-terminus fragment of the parent Aβ peptide were synthesized. The sequential replacement/modification employing unnatural amino acids imparted scaffold diversity, augmented activity, enhanced blood brain barrier permeability and offered proteolytic stability to the synthetic peptides. Several peptides exhibited promising protection against Aβ aggregation-mediated-neurotoxicity in PC-12 cells at doses ranged between 10μM and 0.1μM, further confirmed by the thioflavin-T fluorescence assay. CD study illustrate that these peptides restrict the β-sheet formation, and the non-appearance of Aβ42 fibrillar structures in the electron microscopy confirm the inhibition of Aβ42 aggregation. HRMS and ANS fluorescence spectroscopic anal. provided addnl. mechanistic insights. Two selected lead peptides 5 and 16 depicted enhanced blood-brain penetration and stability against serum and proteolytic enzyme. Structural insights into ligand-Aβ interactions on the monomeric and proto-fibrillar units of Aβ were computationally studied. Promising inhibitory potential and short sequence of the lead peptides offers new avenues for the advancement of peptide-derived therapeutics for AD.

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 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

Zhu, Zhengrong published the artcileDesign and Application of a DNA-Encoded Macrocyclic Peptide Library, HPLC of Formula: 77128-73-5, the publication is ACS Chemical Biology (2018), 13(1), 53-59, database is CAplus and MEDLINE.

A DNA-encoded macrocyclic peptide library was designed and synthesized with 2.4 × 10¹² members composed of 4-20 natural and non-natural amino acids. Affinity-based selection was performed against two therapeutic targets, VHL and RSV N protein. On the basis of selection data, some peptides were selected for resynthesis without a DNA tag, and their activity was confirmed.

ACS 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 C3H7BrO2S, HPLC of Formula: 77128-73-5.

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

Posada, Laura published the artcileFirst total synthesis of versicotide D and analogs, Recommanded Product: (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, the publication is Tetrahedron Letters (2019), 60(48), 151281, database is CAplus.

The first total synthesis of cyclotetrapeptide versicotide D has been achieved in 21% overall yield using solid phase peptide synthesis and solution cyclization. In addition, in the search for candidates of antimalarial new drugs, one cyclic tetrapeptide analog which differs in the sequence, and four cyclic pentapeptide containing N-Me amino acids, were prepared The obtained compounds were evaluated against P. falciparum 3D7. Versicotide D showed low micromolar antiplasmodial activity.

Tetrahedron 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, 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

Qu, Hongchang published the artcileNew analogs of the clinical complement inhibitor compstatin with subnanomolar affinity and enhanced pharmacokinetic properties, Category: ethers-buliding-blocks, the publication is Immunobiology (2013), 218(4), 496-505, database is CAplus and MEDLINE.

Therapeutic modulation of the complement system has become increasingly important in line with the growing recognition of the role of complement in numerous diseases. Compstatin, a peptidic inhibitor that acts at the central level of the complement cascade, is currently in clin. evaluation but routes to improve its efficacy have not yet been fully explored. Here, we report improvements in both the inhibitory potency and pharmacokinetic parameters of compstatin that broaden its clin. applications. Selective modification of the compstatin N-terminus with non-proteinogenic amino acids resulted in the first analog with subnanomolar binding affinity (K_D = 0.5 nM) and other similarly potent derivatives with improved solubility in clin. relevant solvents. Detailed structure-activity relationship studies based on biophys. and computational methods revealed key structural determinants for the observed improvements. Importantly, pharmacokinetic evaluation in non-human primates revealed target-driven elimination kinetics with plasma half-life values exceeding expectations for peptidic drugs (close to 12 h). This successful optimization strategy is expected to pave the way for systemic administration of compstatin in a range of clin. conditions.

Immunobiology 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

Koecher, Steffen published the artcileTailored Ahp-cyclodepsipeptides as Potent Non-covalent Serine Protease Inhibitors, Application of (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, the publication is Angewandte Chemie, International Edition (2017), 56(29), 8555-8558, database is CAplus and MEDLINE.

The S1 serine protease family is one of the largest and most biol. important protease families. Despite their biomedical significance, generic approaches to generate potent, class-specific, bioactive non-covalent inhibitors for these enzymes are still limited. In this work, we demonstrate that Ahp-cyclodepsipeptides represent a suitable scaffold for generating target-tailored inhibitors of serine proteases. For efficient synthetic access, we developed a practical mixed solid- and solution-phase synthesis that we validated through performing the first chem. synthesis of the two natural products Tasipeptin A and B. The suitability of the Ahp-cyclodepsipeptide scaffold for tailored inhibitor synthesis is showcased by the generation of the most potent human HTRA protease inhibitors to date. We anticipate that our approach may also be applied to other serine proteases, thus opening new avenues for a systematic discovery of serine protease inhibitors.

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, 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

Jazayeri, Ali published the artcileCrystal structure of the GLP-1 receptor bound to a peptide agonist, Synthetic Route of 77128-73-5, the publication is Nature (London, United Kingdom) (2017), 546(7657), 254-258, database is CAplus and MEDLINE.

Glucagon-like peptide 1 (GLP-1) regulates glucose homeostasis through the control of insulin release from the pancreas. GLP-1 peptide agonists are efficacious drugs for the treatment of diabetes. To gain insight into the mol. mechanism of action of GLP-1 peptides, here we report the crystal structure of the full-length GLP-1 receptor bound to a truncated peptide agonist. The peptide agonist retains an α-helical conformation as it sits deep within the receptor-binding pocket. The arrangement of the transmembrane helixes reveals hallmarks of an active conformation similar to that observed in class A receptors. Guided by this structural information, we design peptide agonists with potent in vivo activity in a mouse model of diabetes.

Nature (London, 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, Synthetic Route of 77128-73-5.

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

Upadhyaya, Punit published the artcileInhibition of Ras Signaling by Blocking Ras-Effector Interactions with Cyclic Peptides, Safety of (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-phenylpropanoic acid, the publication is Angewandte Chemie, International Edition (2015), 54(26), 7602-7606, database is CAplus and MEDLINE.

Ras genes are frequently activated in human cancers, but the mutant Ras proteins remain largely “undruggable” through the conventional small-mol. approach owing to the absence of any obvious binding pockets on their surfaces. By screening a combinatorial peptide library, followed by structure-activity relationship (SAR) anal., we discovered a family of cyclic peptides possessing both Ras-binding and cell-penetrating properties. These cell-permeable cyclic peptides inhibit Ras signaling by binding to Ras-GTP and blocking its interaction with downstream proteins and they induce apoptosis of cancer cells. Our results demonstrate the feasibility of developing cyclic peptides for the inhibition of intracellular protein-protein interactions and of direct Ras inhibitors as a novel class of anticancer agents.

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 C9H17NO, 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