35737-15-6 | - Page 5 of 10 - Indole Building Blocks

Mukherjee, Nabanita team published research on Israel Journal of Chemistry in | 35737-15-6

35737-15-6, Nalpha-FMOC-L-Tryptophan,also known as Fmoc-Trp-OH， is a useful research compound. Its molecular formula is C26H22N2O4 and its molecular weight is 426.5 g/mol. The purity is usually 95%.
Nα-Fmoc-L-Tryptophan is an N-Fmoc protected form of L-Tryptophan (T947210). L-Tryptophan is an essential amino acid that is important for cell proliferation and the biosynthesis of proteins. It is a precursor to Serotonin (HCl: S274980), a neurotransmitter that compound that aids in sleep and mental state. L-Tryptophan is also thought to cause eosinophilia-myalgia syndrome.
Fmoc-Trp-OH is an amino acid derivative
Fmoc-L-Trp-OH is an amide that contains a low bioavailability and inhibits the transfer of amino acids to ribosomes. It has been shown to inhibit the growth of cancer cells in cell culture and to have antimicrobial activity. Fmoc-L-Trp-OH is synthesized by reacting Naphthalene with glycine, followed by hydrolysis of the ester group under trifluoroacetic acid. The product is then conjugated with a polypeptide. This method of synthesis was developed as a way to produce peptides that are difficult to synthesize using solid-phase chemistry., SDS of cas: 35737-15-6

In addition to indoleacetic acid, indigo, and tryptophan, numerous compounds obtainable from plant or animal sources contain the indole molecular structure. 35737-15-6, formula is C26H22N2O4, Name is Fmoc-Trp-OH. The best-known group of these compounds is the indole alkaloids, members of which have been isolated from plants representing more than 30 families. SDS of cas: 35737-15-6.

Mukherjee, Nabanita;Roy, Rajsekhar;Ghosh, Satyajit;Ghosh, Surajit research published 《 Self-Assembled Antimitotic Peptide Vesicle Designed from α,β-Tubulin Heterodimer Interface for Anticancer Drug Delivery》, the research content is summarized as follows. Peptide based anticancer mol. act simultaneously as potent anticancer therapeutic as well as unique drug delivery vehicle for the targeted delivery of often cytotoxic abysmally bioavailable anticancer drugs to their designated organelle. The atypical self-assembling propensity of peptides gives rise to distinct nanostructures capable of encapsulating various drug payload. Among three different types of cytoskeletons presents in eukaryotes, microtubule plays a quintessential role during the course of cell cycle. Microtubule-targeting agents continues to be the most unwavering classes of antineoplastic drugs for the treatment of cancer. Any intervention to the dynamic tubulin assembly-disassembly process will definitely lead to complete perturbation of total cell division process. Several tubulin targeted antimitotic drugs had been designed as well as discovered to disrupt this dynamic nature of tubulin monomers either by inducing extensive polymerization or depolymerization, thereby facilitating overall cell cycle arrest. However, in cancer cells, aberrant mTOR activity causes growing resistance against numerous tubulin targeted drugs inducing metastasization, and simultaneous invasion to new healthy tissues. In recent years, numerous tubulin targeted drugs have been found to have high activity in a combination with mTOR inhibitors like tacrolimus, everolimus (RAD001), etc. but restrained bioavailability, non-specificity and quick excretion are the major impediments for the successful implementation. Combining the immense importance of protein-peptide interaction for the development of future anticancer therapeutics as well as self-assembling propensity of peptides we have taken a unique approach to craft a microtubule targeting antimitotic peptide designed from α,β-tubulin heterodimer interface, which promotes both in vitro and in vivo tubulin depolymerization, exhibiting middling toxicity towards MCF7 cells, causing cell cycle arrest. Further AFM images of this β-sheet forming peptide reveals that this peptide upon self-assembly give rise to spectacular vesicle structural characteristics which can be used as a vehicle for a combination delivery of Docetaxel and RAD001 in order to enhance their individual therapeutic potency. Encapsulation of propidium iodide and concomitant release studies suggest that Pep-4 vesicles could be a potential candidate for tubulin targeted sustained release of therapeutics. Here, our designed peptide vesicles are found to capable for the delivery of tubulin targeting drug Docetaxel along with an well-known mTOR inhibiting drug RAD001 successfully to breast cancer cell line in order to achieve a robust symbiotic effect.

Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles

Nadal-Bufi, Ferran team published research on Journal of Medicinal Chemistry in 2021 | 35737-15-6

Nadal-Bufi, Ferran;Mason, Jody M.;Chan, Lai Yue;Craik, David J.;Kaas, Quentin;Troeira Henriques, Sonia research published 《 Designed β-Hairpins Inhibit LDH5 Oligomerization and Enzymatic Activity》, the research content is summarized as follows. Lactate dehydrogenase 5 (LDH5) is overexpressed in metastatic tumors and is an attractive target for anticancer therapy. Small-mol. drugs have been developed to target the substrate/cofactor sites of LDH5, but none has reached the clinic to date, and alternative strategies remain almost unexplored. Combining rational and computer-based approaches, we identified peptidic sequences with high affinity toward a β-sheet region that is involved in protein-protein interactions (PPIs) required for the activity of LDH5. To improve stability and potency, these sequences were grafted into a cyclic cell-penetrating β-hairpin peptide scaffold. The lead grafted peptide, cGmC9, inhibited LDH5 activity in vitro in low micromolar range and more efficiently than the small-mol. inhibitor GNE-140. CGmC9 inhibits LDH5 by targeting an interface unlikely to be inhibited by small-mol. drugs. This lead will guide the development of new LDH5 inhibitors and challenges the landscape of drug discovery programs exclusively dedicated to small mols.

Narayanam, Maruthi Kumar team published research on Bioconjugate Chemistry in 2021 | 35737-15-6

Previous studies have identified that indole-oxidases are present in P. putida, whose major ligands are heterocyclic substrates and have an interesting affinity when the substrate is indole. 35737-15-6, formula is C26H22N2O4, Name is Fmoc-Trp-OH. These enzymes oxidize the ring so the substrate turns into Indigo. Synthetic Route of 35737-15-6.

Narayanam, Maruthi Kumar;Lai, Bert T.;Loredo, Jacquie Malette;Wilson, Jere A.;Eliasen, Anders M.;LaBerge, Nicole A.;Nason, Malley;Cantu, Annabelle L.;Luton, Breanna K.;Xu, Shili;Agnew, Heather D.;Murphy, Jennifer M. research published 《 Positron emission tomography tracer design of targeted synthetic peptides via ¹⁸F-sydnone alkyne cycloaddition》, the research content is summarized as follows. Chem. synthesized, small peptides that bind with high affinity and specificity to CD8-expressing (CD8+) tumor-infiltrating T cells, yet retain the desirable characteristics of small mols., hold valuable potential for diagnostic mol. imaging of immune response. Here, we report the development of ¹⁸F-labeled peptides targeting human CD8α with nanomolar affinity via the strain-promoted sydnone-alkyne cycloaddition with 4-[¹⁸F]fluorophenyl sydnone. The ¹⁸F-sydnone is produced in one step, in high radiochem. yield, and the peptide labeling proceeds rapidly. A hydrophilic chem. linker results in a tracer with favorable pharmacokinetic properties and improved image contrast, as demonstrated by in vivo PET imaging studies.

Nestor, John J. team published research on Peptide Science (Hoboken, NJ, United States) in 2021 | 35737-15-6

Synthetic Route of 35737-15-6, Nalpha-FMOC-L-Tryptophan,also known as Fmoc-Trp-OH， is a useful research compound. Its molecular formula is C26H22N2O4 and its molecular weight is 426.5 g/mol. The purity is usually 95%.
Nα-Fmoc-L-Tryptophan is an N-Fmoc protected form of L-Tryptophan (T947210). L-Tryptophan is an essential amino acid that is important for cell proliferation and the biosynthesis of proteins. It is a precursor to Serotonin (HCl: S274980), a neurotransmitter that compound that aids in sleep and mental state. L-Tryptophan is also thought to cause eosinophilia-myalgia syndrome.
Fmoc-Trp-OH is an amino acid derivative
Fmoc-L-Trp-OH is an amide that contains a low bioavailability and inhibits the transfer of amino acids to ribosomes. It has been shown to inhibit the growth of cancer cells in cell culture and to have antimicrobial activity. Fmoc-L-Trp-OH is synthesized by reacting Naphthalene with glycine, followed by hydrolysis of the ester group under trifluoroacetic acid. The product is then conjugated with a polypeptide. This method of synthesis was developed as a way to produce peptides that are difficult to synthesize using solid-phase chemistry., 35737-15-6.

Indole, first isolated in 1866, has the molecular formula C8H7N, and it is commonly synthesized from phenylhydrazine and pyruvic acid, 35737-15-6, formula is C26H22N2O4, Name is Fmoc-Trp-OH. although several other procedures have been discovered.Indole is a colourless solid having a pleasant fragrance in highly dilute solutions. It melts at 52.5° C (126.5° F). Synthetic Route of 35737-15-6.

Nestor, John J.;Wang, Wei research published 《 Surfactant-modified parathyroid hormone fragments with high potency and prolonged action: Structure-informed design using glycolipid surfactant conjugation》, the research content is summarized as follows. The pharmaceutical properties of peptides (high potency and specificity with low toxicity) make them an attractive therapeutic class but typically short duration of action and low bioavailability can limit their usefulness. Here, we begin evaluation of a new class of peptide modification, glycolipid surfactant conjugation, designed to extend the half-life of peptide therapeutics. This work illustrates ease of synthesis and conjugation, range of modulation of pharmacokinetic/pharmacodynamic behavior and acceptability in vivo of this approach. Proof of concept used parathyroid hormone and showed that an N-terminal fragment can be modified, informed by the parathyroid hormone receptor x-ray structure, to produce high potency, enhanced intrinsic efficacy and prolonged action in vivo. This suggests daily (hypoparathyroidism) or weekly (osteoporosis) administration with biol. sequelae (stem cell maturation to osteoblasts) throughout the week. Compound 7 was chosen for advanced study. Exploration of the phys. properties and development potential of glycolipid surfactant-modified peptides are underway with addnl. peptide therapeutics.

Nie, Qigui team published research on Journal of Organic Chemistry in | 35737-15-6

Nie, Qigui;Fang, Xianfu;Liu, Changyang;Zhang, Gong;Fan, Xiaohong;Li, Yangfeng;Li, Yizhou research published 《 DNA-compatible ortho-phthalaldehyde (OPA)-mediated 2-substituted isoindole core formation and applications》, the research content is summarized as follows. A DNA-compatible protocol for ortho-phthalaldehyde-mediated transformation of amines into drug-like moieties represented by isoindolinones and thio-2-isoindoles is reported. The high conversion and wide substrate-scope property of this protocol renders its feasibility in the manipulation of terminal amines on oligonucleotide conjugates, including “cap-and-catch” purification, sequential synthesis during DEL construction and on-DNA macrocyclization.

Norman, Alexander team published research on ACS Central Science in 2021 | 35737-15-6

Norman, Alexander;Franck, Charlotte;Christie, Mary;Hawkins, Paige M. E.;Patel, Karishma;Ashhurst, Anneliese S.;Aggarwal, Anupriya;Low, Jason K. K.;Siddiquee, Rezwan;Ashley, Caroline L.;Steain, Megan;Triccas, James A.;Turville, Stuart;Mackay, Joel P.;Passioura, Toby;Payne, Richard J. research published 《 Discovery of cyclic peptide ligands to the SARS-CoV-2 spike protein using mRNA display》, the research content is summarized as follows. The COVID-19 pandemic, caused by SARS-CoV-2, has led to substantial morbidity, mortality, and disruption globally. Cellular entry of SARS-CoV-2 is mediated by the viral spike protein, and affinity ligands to this surface protein have the potential for applications as antivirals and diagnostic reagents. Here, we describe the affinity selection of cyclic peptide ligands to the SARS-CoV-2 spike protein receptor binding domain (RBD) from three distinct libraries (in excess of a trillion mols. each) by mRNA display. We identified six high affinity mols. with dissociation constants (K_D) in the nanomolar range (15-550 nM) to the RBD. The highest affinity ligand could be used as an affinity reagent to detect the spike protein in solution by ELISA, and the cocrystal structure of this mol. bound to the RBD demonstrated that it binds to a cryptic binding site, displacing a β-strand near the C-terminus. Our findings provide key mechanistic insight into the binding of peptide ligands to the SARS-CoV-2 spike RBD, and the ligands discovered in this work may find future use as reagents for diagnostic applications.

Malik, Uru team published research on Peptide Science (Hoboken, NJ, United States) in 2021 | 35737-15-6

HPLC of Formula: 35737-15-6, Nalpha-FMOC-L-Tryptophan,also known as Fmoc-Trp-OH， is a useful research compound. Its molecular formula is C26H22N2O4 and its molecular weight is 426.5 g/mol. The purity is usually 95%.
Nα-Fmoc-L-Tryptophan is an N-Fmoc protected form of L-Tryptophan (T947210). L-Tryptophan is an essential amino acid that is important for cell proliferation and the biosynthesis of proteins. It is a precursor to Serotonin (HCl: S274980), a neurotransmitter that compound that aids in sleep and mental state. L-Tryptophan is also thought to cause eosinophilia-myalgia syndrome.
Fmoc-Trp-OH is an amino acid derivative
Fmoc-L-Trp-OH is an amide that contains a low bioavailability and inhibits the transfer of amino acids to ribosomes. It has been shown to inhibit the growth of cancer cells in cell culture and to have antimicrobial activity. Fmoc-L-Trp-OH is synthesized by reacting Naphthalene with glycine, followed by hydrolysis of the ester group under trifluoroacetic acid. The product is then conjugated with a polypeptide. This method of synthesis was developed as a way to produce peptides that are difficult to synthesize using solid-phase chemistry., 35737-15-6.

Malik, Uru;Chan, Lai Yue;Cai, Minying;Hruby, Victor J.;Kaas, Quentin;Daly, Norelle L.;Craik, David J. research published 《 Development of novel frog-skin peptide scaffolds with selectivity towards melanocortin receptor subtypes》, the research content is summarized as follows. Melanocortin receptors are pharmaceutically important receptors that are involved in complex physiol. functions. They have been associated with various diseases including obesity, erectile dysfunction, acne, and skin cancer. It has been challenging to transform nonselective endogenous agonist and antagonist ligands into selective and potent ligands. In this study, we investigated naturally occurring peptides derived from frog skin secretions for selectivity and activity toward melanocortin receptors. Three peptides (ORB, ORB2K and ranacyclin-T) were found to have selectivity towards the melanocortin receptor 5 (MC5R). ORB and ORB2K had partial binding affinity at nanomolar concentrations, whereas ranacyclin-T had 57% binding efficiency at 1.6μM. Backbone cyclization of ORB and ORB2K altered the binding efficiency to melanocortin receptors. Our results suggest that these frog-skin peptides could be modified for developing melanocortin-specific ligands and potentially future therapeutics.

Mao, Runyu team published research on Journal of the American Chemical Society in 2021 | 35737-15-6

Mao, Runyu;Xi, Shiyi;Shah, Sayali;Roy, Michael J.;John, Alan;Lingford, James P.;Gade, Gerd;Scott, Nichollas E.;Goddard-Borger, Ethan D. research published 《 Synthesis of C-mannosylated glycopeptides enabled by Ni-catalyzed photoreductive cross-coupling reactions》, the research content is summarized as follows. The biol. functions of tryptophan C-mannosylation are poorly understood, in part, due to a dearth of methods for preparing pure glycopeptides and glycoproteins with this modification. To address this issue, efficient and scalable methods are required for installing this protein modification. Here, we describe unique Ni-catalyzed cross-coupling conditions that utilize photocatalysis or a Hantzsch ester photoreductant to couple glycosyl halides with (hetero)aryl bromides, thereby enabling the α-C-mannosylation of 2-bromo-tryptophan, peptides thereof, and (hetero)aryl bromides more generally. We also report that 2-(α-D-mannopyranosyl)-L-tryptophan undergoes facile anomerization in the presence of acid: something that must be considered when preparing and handling peptides with this modification. These developments enabled the first automated solid-phase peptide syntheses of C-mannosylated glycopeptides, which we used to map the epitope of an antibody, as well as providing the first verified synthesis of Carmo-HrTH-I, a C-mannosylated insect hormone. To complement this approach, we also performed late-stage tryptophan C-mannosylation on a diverse array of peptides, demonstrating the broad scope and utility of this methodol. for preparing glycopeptides.

Mallek, Aaron J. team published research on Angewandte Chemie, International Edition in 2021 | 35737-15-6

Mallek, Aaron J.;Pentelute, Bradley L.;Buchwald, Stephen L. research published 《 Selective N-arylation of p-aminophenylalanine in unprotected peptides with organometallic palladium reagents》, the research content is summarized as follows. The selective N-arylation of p-aminophenylalanine in polypeptides with pre-formed palladium oxidative addition complexes is described. The depressed pKa of the aniline NH₂ group enables chemoselective C-N bond formation on peptides containing multiple other aliphatic amino groups at lysines or the N-terminus via Curtin-Hammett control under mild conditions. Using palladium complexes derived from electron-poor aryl halides, p-aminophenylalanine is fully arylated in aqueous buffer in as little as one hour at micromolar concentrations A complementary protocol using the non-nucleophilic, organic base 1,5-diazabicyclo(4.3.0)non-5-ene (DBN), expands the substrate scope to tolerate electron-rich functional groups provides up to 97% conversion. These procedures enable the chemoselective conjugation of functionally diverse small mol. pharmaceuticals to p-aminophenylalanine containing derivatives of cell-penetrating peptides.

Malayam Parambath, Sreya team published research on ChemSusChem in 2021 | 35737-15-6

Malayam Parambath, Sreya;Williams, Ashley E.;Hunt, Leigh Anna;Selvan, Dhanashree;Hammer, Nathan I.;Chakraborty, Saumen research published 《 A De Novo-Designed Artificial Metallopeptide Hydrogenase: Insights into Photochemical Processes and the Role of Protonated Cys》, the research content is summarized as follows. Hydrogenase enzymes produce H₂ gas, which can be a potential source of alternative energy. Inspired by the [NiFe] hydrogenases, we report the construction of a de novo-designed artificial hydrogenase (ArH). The ArH is a dimeric coiled coil where two cysteine (Cys) residues are introduced at tandem a/d positions of a heptad to create a tetrathiolato Ni binding site. Spectroscopic studies show that Ni binding significantly stabilizes the peptide producing electronic transitions characteristic of Ni-thiolate proteins. The ArH produces H₂ photocatalytically, demonstrating a bell-shaped pH-dependence on activity. Fluorescence lifetimes and transient absorption spectroscopic studies are undertaken to elucidate the nature of pH-dependence, and to monitor the reaction kinetics of the photochem. processes. PH titrations are employed to determine the role of protonated Cys on reactivity. Through combining these results, a fine balance is found between solution acidity and the electron transfer steps. This balance is critical to maximize the production of Ni^I-peptide and protonation of the Ni^II-H^– intermediate (Ni-R) by a Cys (pK_a≈6.4) to produce H₂.