Category: 71989-31-6

Brousseau, Margaret E. published the artcileIdentification of a PCSK9-LDLR disruptor peptide with in vivo function, Quality Control of 71989-31-6, 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 71989-31-6. 71989-31-6 belongs to catalysis-chemistry, auxiliary class Amino acide derivatives,pyrrolidine, name is Fmoc-Pro-OH, and the molecular formula is C20H19NO4, Quality Control of 71989-31-6.

Referemce:
https://courses.lumenlearning.com/boundless-chemistry/chapter/catalysis/,
Catalysis – Wikipedia

Jamaluddin, Aqfan published the artcileLipidated calcitonin gene-related peptide (CGRP) peptide antagonists retain CGRP receptor activity and attenuate CGRP Action In Vivo, Product Details of C20H19NO4, the publication is Frontiers in Pharmacology (2022), 832589, database is CAplus and MEDLINE.

Signaling through calcitonin gene-related peptide (CGRP) receptors is associated with pain, migraine, and energy expenditure. Small mol. and monoclonal antibody CGRP receptor antagonists that block endogenous CGRP action are in clin. use as antimigraine therapies. By comparison, the potential utility of peptide antagonists has received less attention due to suboptimal pharmacokinetic properties. Lipidation is an established strategy to increase peptide half-life in vivo. This study aimed to explore the feasibility of developing lipidated CGRP peptide antagonists that retain receptor antagonist activity in vitro and attenuate endogenous CGRP action in vivo. CGRP peptide analogs based on the archetypal CGRP receptor antagonist, CGRP8-37, were palmitoylated at the N-terminus, position 24, and near the C-terminus at position 35. The antagonist activities of the lipidated peptide analogs were tested in vitro using transfected Cos7 cells expressing either the human or mouse CGRP receptor, amylin subtype 1 (AMY1) receptor, adrenomedullin (AM) receptors, or calcitonin receptor. Antagonist activities were also evaluated in SK-N-MC cells that endogenously express the human CGRP receptor. Lipidated peptides were then tested for their ability to antagonize endogenous CGRP action in vivo using a capsaicin-induced dermal vasodilation (CIDV) model in C57/BL6J mice. All lipidated peptides except for the C-terminally modified analog retained potent antagonist activity compared to CGRP8-37 towards the CGRP receptor. The lipidated peptides also retained, and sometimes gained, antagonist activities at AMY1, AM1 and AM2 receptors. Several lipidated peptides produced robust inhibition of CIDV in mice. This study demonstrates that selected lipidated peptide antagonists based on ¦ÁCGRP8-37 retain potent antagonist activity at the CGRP receptor and are capable of inhibition of endogenous CGRP action in vivo. These findings suggest that lipidation can be applied to peptide antagonists, such as ¦ÁCGRP8-37 and are a potential strategy for antagonizing CGRP action.

Frontiers in Pharmacology published new progress about 71989-31-6. 71989-31-6 belongs to catalysis-chemistry, auxiliary class Amino acide derivatives,pyrrolidine, name is Fmoc-Pro-OH, and the molecular formula is C20H19NO4, Product Details of C20H19NO4.

Referemce:
https://courses.lumenlearning.com/boundless-chemistry/chapter/catalysis/,
Catalysis – Wikipedia

Fleming, Matthew C. published the artcileDiscovery and Structural Basis of the Selectivity of Potent Cyclic Peptide Inhibitors of MAGE-A4, Related Products of catalysis-chemistry, the publication is Journal of Medicinal Chemistry (2022), 65(10), 7231-7245, database is CAplus and MEDLINE.

MAGE proteins are cancer testis antigens (CTAs) that are characterized by highly conserved MAGE homol. domains (MHDs) and are increasingly being found to play pivotal roles in promoting aggressive cancer types. MAGE-A4, in particular, increases DNA damage tolerance and chemoresistance in a variety of cancers by stabilizing the E3-ligase RAD18 and promoting trans-lesion synthesis (TLS). Inhibition of the MAGE-A4:RAD18 axis could sensitize cancer cells to chemotherapeutics like platinating agents. We use an mRNA display of thioether cyclized peptides to identify a series of potent and highly selective macrocyclic inhibitors of the MAGE-A4:RAD18 interaction. Co-crystal structure indicates that these inhibitors bind in a pocket that is conserved across MHDs but take advantage of A4-specific residues to achieve high isoform selectivity. Cumulatively, our data represent the first reported inhibitor of the MAGE-A4:RAD18 interaction and establish biochem. tools and structural insights for the future development of MAGE-A4-targeted cellular probes.

Journal of Medicinal Chemistry published new progress about 71989-31-6. 71989-31-6 belongs to catalysis-chemistry, auxiliary class Amino acide derivatives,pyrrolidine, name is Fmoc-Pro-OH, and the molecular formula is C20H19NO4, Related Products of catalysis-chemistry.

Referemce:
https://courses.lumenlearning.com/boundless-chemistry/chapter/catalysis/,
Catalysis – Wikipedia

Fan, Jinda published the artcileMultifunctional Thio-Stabilized Gold Nanoparticles for Near-Infrared Fluorescence Detection and Imaging of Activated Caspase-3, Recommanded Product: Fmoc-Pro-OH, the publication is Current Analytical Chemistry (2021), 17(8), 1182-1193, database is CAplus and MEDLINE.

Gold nanoparticles (AuNPs) are commonly used in nanomedicine because of their unique spectral properties, chem. and biol. stability, and ability to quench the fluorescence of organic dyes attached to their surfaces. However, the utility of spherical AuNPs for activatable fluorescence sensing of mol. processes have been confined to resonance-matched fluorophores in the 500 nm to 600 nm spectral range to maximize dye fluorescence quenching efficiency. Expanding the repertoire of fluorophore systems into the NIR fluorescence regimen with emission >800 nm will facilitate the anal. of multiple biol. events with high detection sensitivity. The primary goal of this study is to determine if spherical AuNP-induced radiative rate suppression of non-resonant near-IR (NIR) fluorescent probes can serve as a versatile nanoconstruct for highly sensitive detection and imaging of activated caspase-3 in aqueous media and cancer cells. This required the development of activatable NIR fluorescence sensors of caspase-3 designed to overcome the nonspecific degradation and release of the surface coatings in aqueous media. We harnessed the fluorescence-quenching properties and multivalency of spherical AuNPs to develop AuNP-templated activatable NIR fluorescent probes to detect activated caspase-3, an intracellular reporter of early cell death. Freshly AuNPs were coated with a multifunctional NIR fluorescent dye-labeled peptide (LS422) consisting of an RGD peptide sequence that targets ¦Áv¦Â3 -integrin protein (¦Áv¦Â3)on the surface of cancer cells to mediate the uptake and internalization of the sensors in tumor cells; a DEVD peptide sequence for reporting the induction of cell death through caspase-3 mediated NIR fluorescence enhancement; and a multidentate hexacysteine sequence for enhancing self-assembly and stabilizing the multifunctional construct on AuNPs. The integrin-binding affinity of LS422 and caspase-3 kinetics were determined by competitive radioligand binding and fluorogenic peptide assays, resp. Detection of intracellular caspase-3, cell viability, and the internalization of LS422 in cancer cells was determined by confocal NIR fluorescence spectroscopy and microscopy. Narrow size AuNPs (13 nm) were prepared and characterized by transmission electron microscopy and dynamic light scattering. When assembled on the AuNPs, the binding constant of LS422 for¦Áv¦Â3 improved 11- fold from 13.2 nM to 1.2 nM. Whereas the catalytic turnover of caspase-3 by LS422-AuNPs was similar to the reference fluorogenic peptide, the binding affinity for the enzyme increased by a factor of 2. Unlike the ¦Áv¦Â3 pos., but caspase-3 neg. breast cancer MCF-7 cells, treatment of the ¦Áv¦Â3 and caspase-3 pos. lung cancer A549 cells with Paclitaxel showed significant fluorescence enhancement within 30 min, which correlated with caspase-3 specific activation of LS422-AuNPs fluorescence. The incorporation of a 3.5 mW NIR laser source into our spectrofluorometer increased the detection sensitivity by an order of magnitude (limit of detection ?0.1 nM of cypate) and significantly decreased the signal noise relative to a xenon lamp. This gain in sensitivity enabled the detection of substrate hydrolysis at a broad range of inhibitor concentrations without photobleaching the cypate dye. The multifunctional AuNPs demonstrate the use of a non-resonant quenching strategy to design activatable NIR fluorescence mol. probes. The nanoconstruct offers a selective reporting method for detecting activated caspase-3, imaging of cell viability, identifying dying cells, and visualizing the functional status of intracellular enzymes. Performing these tasks with NIR fluorescent probes creates an opportunity to translate the in vitro and cellular anal. of enzymes into in vivo interrogation of their functional status using deep tissue penetrating NIR fluorescence anal. methods.

Current Analytical Chemistry published new progress about 71989-31-6. 71989-31-6 belongs to catalysis-chemistry, auxiliary class Amino acide derivatives,pyrrolidine, name is Fmoc-Pro-OH, and the molecular formula is C20H19NO4, Recommanded Product: Fmoc-Pro-OH.

Referemce:
https://courses.lumenlearning.com/boundless-chemistry/chapter/catalysis/,
Catalysis – Wikipedia

Ni, Xiu-Wen published the artcileA photocontrollable thermosensitive chemical spatiotemporally destabilizes mitochondrial membranes for cell fate manipulation, Application In Synthesis of 71989-31-6, the publication is Biomaterials Science (2022), 10(10), 2550-2556, database is CAplus and MEDLINE.

Perturbations in mitochondrial membrane stability lead to cytochrome c release and induce caspase-dependent apoptosis. Using synthetic smart chems. with changeable physicochem. properties to interfere the mitochondrial membrane stability has not yet been reported. Here we show that a thermosensitive anchor-polymer-peptide conjugate (anchor-PPC) destabilizes mitochondrial membranes upon in situ mol. changes from hydrophilic to hydrophobic, which consequently induces apoptosis in a spatiotemporally controlled manner and acts as an antitumor pharmaceutical. The anchor-PPC is composed of a thermosensitive copolymer, a photolabile linker, a hydrophilic HIV Tat-derived peptide both for cell penetration and polymer phase transition temperature (Tt) modulation, and an anchor peptide for intercalating into mitochondrial membranes. The photocontrollable anchor-PPC dehydrates and changes from being hydrophilic to hydrophobic upon photoactivation at body temperature This cell-penetrable anchor-PPC specifically targets mitochondria and destabilizes mitochondrial membranes upon irradiation, and consequently initiates apoptosis in cells and a complex 3D tumor model. This study provides the first exptl. evidence that the synthetic smart chem. can spatiotemporally control the stability of organelle membranes based on its in situ physicochem. property change.

Biomaterials Science published new progress about 71989-31-6. 71989-31-6 belongs to catalysis-chemistry, auxiliary class Amino acide derivatives,pyrrolidine, name is Fmoc-Pro-OH, and the molecular formula is C20H19NO4, Application In Synthesis of 71989-31-6.

Referemce:
https://courses.lumenlearning.com/boundless-chemistry/chapter/catalysis/,
Catalysis – Wikipedia

Ayurini, Meri published the artcilePolymer end group control through a decarboxylative cobalt-mediated radical polymerization: new avenues for synthesizing peptide, protein and nanomaterial conjugates, Quality Control of 71989-31-6, the publication is JACS Au (2022), 2(1), 169-177, database is CAplus and MEDLINE.

Cobalt-mediated radical polymerizations (CMRPs) have been initiated by the radical decarboxylation of tetrachlorophthalimide activated esters. This allows for the controlled radical polymerization of activated monomers across a broad temperature range with a single cobalt species, with incorporation of polymer end groups derived from simple carboxylic acids derivatives and termination with an organozinc reagent. This method has been applied to the synthesis of a polymer/graphene conjugate and a water-soluble protein/polymer conjugate, demonstrating the first examples of CMRP in graphene and protein conjugation.

JACS Au published new progress about 71989-31-6. 71989-31-6 belongs to catalysis-chemistry, auxiliary class Amino acide derivatives,pyrrolidine, name is Fmoc-Pro-OH, and the molecular formula is C20H19NO4, Quality Control of 71989-31-6.

Referemce:
https://courses.lumenlearning.com/boundless-chemistry/chapter/catalysis/,
Catalysis – Wikipedia

Yang, Su published the artcileModular Design of Supramolecular Ionic Peptides with Cell-Selective Membrane Activity, Related Products of catalysis-chemistry, the publication is ChemBioChem (2021), 22(22), 3164-3168, database is CAplus and MEDLINE.

The rational design of materials with cell-selective membrane activity is an effective strategy for the development of targeted mol. imaging and therapy. Here we report a new class of cationic multidomain peptides (MDPs) that can undergo enzyme-mediated mol. transformation followed by supramol. assembly to form nanofibers in which cationic clusters are presented on a rigid ¦Â-sheet backbone. This structural transformation, which is induced by cells overexpressing the specific enzymes, led to a shift in the membrane perturbation potential of the MDPs, and consequently enhanced cell uptake and drug delivery efficacy. We envision the directed self-assembly based on modularly designed MDPs as a highly promising approach to generate dynamic supramol. nanomaterials with emerging membrane activity for a range of disease targeted mol. imaging and therapy applications.

ChemBioChem published new progress about 71989-31-6. 71989-31-6 belongs to catalysis-chemistry, auxiliary class Amino acide derivatives,pyrrolidine, name is Fmoc-Pro-OH, and the molecular formula is C15H14O, Related Products of catalysis-chemistry.

Referemce:
https://courses.lumenlearning.com/boundless-chemistry/chapter/catalysis/,
Catalysis – Wikipedia

Fumagalli, Gabriele published the artcileTargeting a novel KRAS binding site: Application of one-component stapling of small (5-6-mer) peptides, Recommanded Product: Fmoc-Pro-OH, the publication is Journal of Medicinal Chemistry (2021), 64(23), 17287-17303, database is CAplus and MEDLINE.

RAS proteins are central in the proliferation of many types of cancer, but a general approach toward the identification of pan-mutant RAS inhibitors has remained unresolved. In this work, we describe the application of a binding pharmacophore identified from anal. of known RAS binding peptides to the design of novel peptides. Using a chem. divergent approach, we generated a library of small stapled peptides from which we identified compounds with weak binding activity. Exploration of structure-activity relationships (SARs) and optimization of these early compounds led to low-micromolar binders of KRAS that block nucleotide exchange.

Journal of Medicinal Chemistry published new progress about 71989-31-6. 71989-31-6 belongs to catalysis-chemistry, auxiliary class Amino acide derivatives,pyrrolidine, name is Fmoc-Pro-OH, and the molecular formula is C20H19NO4, Recommanded Product: Fmoc-Pro-OH.

Referemce:
https://courses.lumenlearning.com/boundless-chemistry/chapter/catalysis/,
Catalysis – Wikipedia

Distefano, Alessia published the artcileCarbon dots surface chemistry drives fluorescent properties: New tools to distinguish isobaric peptides, HPLC of Formula: 71989-31-6, the publication is Journal of Colloid and Interface Science (2022), 405-414, database is CAplus and MEDLINE.

The possibility to design rational carbon dots surface functionalization for specific anal. and bioanal. applications is hindered by the lack of a full knowledge of the surface chem. features driving fluorescent properties. In this model study, we have synthesized four different peptides, three of which are isobaric and not distinguishable by common MSMS experiments After having characterized the peptides conformations by CD analyses, we have covalently bonded all four peptides to carbon dots by using different exptl. procedures, which produce different functional groups on the carbon dots surface. The peptide orientations obtained on the differently functionalized surface of the nanoparticles were different and produced different fluorescent responses. The reported results indicate the possibility to design amino and carboxyl enriched surface carbon dots to answer specific chem. requirements, paving the way for the use of these nanoparticles as a versatile and useful new chem. and biochem. tool.

Journal of Colloid and Interface Science published new progress about 71989-31-6. 71989-31-6 belongs to catalysis-chemistry, auxiliary class Amino acide derivatives,pyrrolidine, name is Fmoc-Pro-OH, and the molecular formula is C20H19NO4, HPLC of Formula: 71989-31-6.

Referemce:
https://courses.lumenlearning.com/boundless-chemistry/chapter/catalysis/,
Catalysis – Wikipedia

Wester, Anita published the artcileEvaluation of 1H-Triazole-1-[N,N’-bis(tert-butoxycarbonyl)]carboxamidine in solution-phase and on-resin guanidinylation, Related Products of catalysis-chemistry, the publication is Journal of Organic Chemistry (2021), 86(21), 14371-14380, database is CAplus and MEDLINE.

Several guanidines and guanidinylated peptides have substantial potential as therapeutics, but efficient guanidinylation reagents are vital for easy access to these compounds Presently, pyrazole-1-carboxamidine type reagents are commonly used in the transformations of amines into corresponding guanidines. Here, we report a comparative study of the utility of 1H-triazole-1-[N,N’-bis(tert-butoxycarbonyl)]carboxamidine, which was synthesized in two steps and readily upscaled to gram amounts It exhibited excellent performance in solution-phase reactions, rapidly converting a set of representative aliphatic primary and unhindered secondary amines as well as aniline into the corresponding bis(tert-butoxycarbonyl)-protected guanidines. To enable a direct assessment of the reactivity of guanidinylation reagents, conversions were performed in deuterated solvents (d₇-DMF or d₈-THF), allowing for continuous anal. of the reaction mixtures by ¹H and ¹³C NMR. Likewise, 1H-triazole-1-[N,N’-bis(tert-butoxycarbonyl)]carboxamidine proved to be a versatile reagent in solid-phase conversions, for example, a resin-bound test peptide (KFFKFFK) was fully guanidinylated in only 2 h by using 2 equiv of the reagent per free amino group. Also, 1H-triazole-1-[N,N’-bis(tert-butoxycarbonyl)]carboxamidine proved capable of completely guanidinylating more sterically hindered N-terminal residues (e.g., N-Me amino acids or a peptoid) in resin-bound peptides. Its superior reactivity and stability demonstrated under heating conditions make 1H-triazole-1-[N,N’-bis(tert-butoxycarbonyl)]carboxamidine a valuable guanidinylation reagent both in solution- and solid-phase synthesis.

Journal of Organic Chemistry published new progress about 71989-31-6. 71989-31-6 belongs to catalysis-chemistry, auxiliary class Amino acide derivatives,pyrrolidine, name is Fmoc-Pro-OH, and the molecular formula is C17H16O2, Related Products of catalysis-chemistry.

Referemce:
https://courses.lumenlearning.com/boundless-chemistry/chapter/catalysis/,
Catalysis – Wikipedia