Tryptophan Derivatives Research Articles

Quinine as a highly responsive chiral sensor for the 1H and 19F NMR enantiodiscrimination of N-trifluoroacetyl amino acids with free carboxyl functions.

Hydrogen-bond accepting and enantiodiscriminating abilities of quinine (Qui) have been exploited in the enantiodiscrimination of N-trifluoroacetyl (TFA) derivatives of amino acids by nuclear magnetic resonance (NMR) spectroscopy. 1H and 19F NMR resonances of derivatives of alanine, valine, leucine, norvaline, phenylalanine, phenylglycine, methionine, glutamic acid, proline, and tryptophan were well differentiated employing CDCl3 and/or C6D6 as solvent, with Qui acting in some cases not only as enantiodiscriminating agent, but also as solubility promoter. For derivatives soluble in both solvents, the best results were obtained in benzene-d6, with very high nonequivalence values, which were detectable not only starting from very low equimolar concentrations of 0.1 mM, but also in the presence of sub-stoichiometric amounts of Qui. The quality of enantiodifferentiation has been also evaluated by means of the enantioresolution quotient E. The method has been applied to the detection and quantification of mixtures of amino acid derivatives by single point measurements.

The Multiomics Analyses of Gut Microbiota, Urine Metabolome and Plasma Proteome Revealed Significant Changes in Allergy Featured with Indole Derivatives of Tryptophan.

ObjectiveTo explore changes in the gut microbiota (GM), urine metabolome and plasma proteome in individuals with allergies using multiomics analyses, and identify the key components and mechanism.MethodsThis was a cross-sectional study. All subjects were recruited to collect fecal, urine and blood samples. 16S rDNA sequencing was used to analyze the structure and function of the GM, liquid chromatography mass spectrometry was used to quantify metabolites in the urine, and data-independent acquisition quantitative proteome analysis was used to detect proteins in the plasma. Differences in GM, urine metabolites and plasma proteins between allergic and healthy individuals were displayed using principal component analysis (PCoA) and heatmap, and the co-occurrence network was visualized in Cytoscape using Spearman correlation among differential predominant genera, metabolites and proteins. The functional analysis was performed according to the Kyoto Encyclopedia of Genes and Genomes (KEGG) dataset. The allergy-related cytokines, IL-4, IL-6 and IL-13, were measured to evaluate the effect of indole derivatives on LPS-induced macrophage activation.ResultsGM α indexes, β distances and the relative abundance of the core differential genera in the allergic group were different from those of healthy individuals, which resulted in a separate distribution in the PCoA and enterotypes. Similarly, the concentrations of 393 metabolites and 144 proteins were different between allergic and healthy individuals. Then, 634 significant correlations were identified among 6 predominant differential genera, 24 differential metabolites and 104 differential proteins, 301 of which were negative and 333 of which were positive. Notably, a core network centered on tryptophan metabolites, indole-3-butyric acid (IBA) and indole-3-lactic acid (ILA), displayed high consistency with the results of KEGG pathway analysis. In the LPS-stimulated macrophages, IBA reduced the expression of IL-4 and IL-6, and ILA inhibited the upregulation of IL-6.ConclusionThe GM, urine metabolome and plasma proteome underwent systematic change in allergic individuals compared to healthy individuals, among which indole derivatives from tryptophan metabolism might play key roles in the progression of allergies and could serve as therapeutic targets of allergy.

Brønsted acid catalyzed enantioselective addition of hydrazones to 3-indolylmethanols

A metal-free synthesis of enantiopure β-substituted tryptophan derivatives was developed. A chiral Brønsted acid enabled the addition of donor-substituted hydrazones to 3-indolylmethanols in excellent yields and enantioselectivities.

Tomato S Ystemin Induces Resistance Against Plectosphaerella Cu Cumerina in Arabidopsis Through the Induction of Phenolic Compounds and Priming of Tryptophan Derivatives

Tomato S Ystemin Induces Resistance Against Plectosphaerella Cu Cumerina in Arabidopsis Through the Induction of Phenolic Compounds and Priming of Tryptophan Derivatives

Rapid and efficient syntheses of tryptophans using a continuous-flow quaternization-substitution reaction of gramines with a chiral nucleophilic glycine equivalent.

A continuous-flow quaternization reaction of gramines with MeI (<1 min) followed by a substitution reaction with a chiral nucleophilic glycine-derived Ni-complex (S)-2 (<1 min) has successfully been developed to afford the corresponding alkylated Ni-complexes 3 in good yields with excellent diastereoselectivity, based on the results of a one-pot quaternization-substitution reaction of gramines with (S)-2 in a batch process. The continuous-flow process allowed the safe and efficient scale-up synthesis of 3j (84% yield, 99% de, 540 g h-1) to give 7-azatryptophan derivative (S)-4j readily by an acid-catalyzed hydrolysis reaction followed by protection with an Fmoc group. The present method for the rapid and efficient syntheses of enantiopure unnatural tryptophan derivatives from various gramines and (S)-2 will be useful to further promote peptide and protein drug discovery and development research.

Preparation, Diagnosis and Evaluation of Cyclic-Tryptophan Derivatives as Anti Breast cancer Agents

The importance of research lies in the treatment of cancerous tumors due to the spread of cancerous tumors in recent decades, so researchers have to insist on finding alternative and more treatments safe from chemotherapy and radiation, which are derivatives of some amino acids, which we attended in our current research. Also, some research showed that taking tryptophan for 3 days before exercise can improve energy and efficiency during exercise, but other preliminary research shows that taking tryptophan during exercise does not improve endurance during cycling exercises. For a few days before exercise to notice any benefit. In this research, we prepared derivatives of cyclic tryptophan and studied their efficacy as anti-tumors, and they gave good results in reducing the size of cancerous tumors and reducing their spread in the body., then sympathy all synthesized new cyclic-tryptophan compounds by numerous techniques (FT.IR ,H.NMR)–spectrophotometric, other physical and chemical properties ,with studying for one of new prepared derivatives as anti breast cancer.

Unsaturated fatty acids and a prenylated tryptophan derivative from a rare actinomycete of the genus Couchioplanes.

A genome mining survey combined with metabolome analysis of publicly available strains identified Couchioplanes sp. RD010705, a strain belonging to an underexplored genus of rare actinomycetes, as a producer of new metabolites. HPLC-DAD-guided fractionation of its fermentation extracts resulted in the isolation of five new methyl-branched unsaturated fatty acids, (2E,4E)-2,4-dimethyl-2,4-octadienoic acid (1), (2E,4E)-2,4,7-trimethyl-2,4-octadienoic acid (2), (R)-(−)-phialomustin B (3), (2E,4E)-7-hydroxy-2,4-dimethyl-2,4-octadienoic acid (4), (2E,4E)-7-hydroxy-2,4,7-trimethyl-2,4-octadienoic acid (5), and one prenylated tryptophan derivative, 6-(3,3-dimethylallyl)-N-acetyl-ʟ-tryptophan (6). The enantiomer ratio of 4 was determined to be approximately S/R = 56:44 by a recursive application of Trost’s chiral anisotropy analysis and chiral HPLC analysis of its methyl ester. Compounds 1–5 were weakly inhibitory against Kocuria rhizophila at MIC 100 μg/mL and none were cytotoxic against P388 at the same concentration.

Tryptophan derivatives, phenolic compounds and antioxidant potential of some wildTanacetum taxa from Turkey

Tryptophan derivatives, phenolic compounds and antioxidant potential of some wildTanacetum taxa from Turkey

Total Synthesis of (-)-Calycanthine via Iron-Catalyzed Stereoselective Oxidative Dimerization.

Dimeric cyclotryptamine alkaloids typically feature vicinal all-carbon quaternary stereocenters and four nitrogen atoms. In comparison with the actual biosynthetic tryptophan derivatives, we designed the 2N-featured monomer 7, aiming to construct vicinal all-carbon quaternary stereocenters via a one-step dimerization process to access the 4N-featured isomeric members of this family. In this work, we disclose the first synthetic route to access the skeleton of (-)-isocalycanthine, featuring an iron-catalyzed oxidative dimerization reaction in a catalytic single-step operation with an overwhelming control of the absolute and relative stereochemistry. This strategy has been successfully applied to the total synthesis of (-)-calycanthine and 16 isocalycanthine derivatives, which demonstrates a new synthetic pathway for dimeric cyclotryptamine alkaloids.

Bifidobacterium breve CCFM1025 attenuates major depression disorder via regulating gut microbiome and tryptophan metabolism: A randomized clinical trial

ObjectivePsychobiotics, as a novel class of probiotics mainly acting on the gut-brain axis, have shown promising prospects in treating psychiatric disorders. Bifidobacterium breve CCFM1025 was validated to have an antidepressant-like effect in mice. This study aims to assess its psychotropic potential in managing major depression disorder (MDD) and unravel the underlying mechanisms. MethodsClinical Trial Registration: https://www.chictr.org.cn/index.aspx (identifier: NO. ChiCTR2100046321). Patients (n = 45) diagnosed with MDD were randomly assigned to the Placebo (n = 25) and CCFM1025 (n = 20) groups. The freeze-dried CCFM1025 in a dose of viable bacteria of 1010 CFU was given to MDD patients daily for four weeks, while the placebo group was given maltodextrin. Changes from baseline in psychometric and gastrointestinal symptoms were evaluated using Hamilton Depression Rating scale-24 Items (HDRS-24), Montgomery-Asberg Depression Rating Scale (MADRS), Brief Psychiatric Rating Scale (BPRS), and Gastrointestinal Symptom Rating Scale (GSRS). Serum measures were also determined, i.e., cortisol, TNF-α, and IL-β. Serotonin turnover in the circulation, gut microbiome composition, and tryptophan metabolites were further investigated for clarifying the probiotics’ mechanisms of action. ResultsCCFM1025 showed a better antidepressant-like effect than placebo, based on the HDRS-24 (placebo: M = 6.44, SD = 5.44; CCFM1025: M = 10.40, SD = 6.85; t(43) = 2.163, P = 0.036, d = 0.640) and MADRS (placebo: M = 4.92, SD = 7.15; CCFM1025: M = 9.60, SD = 7.37; t(43) = 2.152, P = 0.037, d = 0.645) evaluation. The factor analysis of BPRS and GSRS suggested that patients’ emotional and gastrointestinal problems may be affected by the serotonergic system. Specifically, CCFM1025 could significantly and to a larger extend reduce the serum serotonin turnover compared with the placebo (placebo: M = -0.01, SD = 0.41; CCFM1025: M = 0.27, SD = 0.40; t(43) = 2.267, P = 0.029, d = 0.681). It may be due to changes in gut microbiome and gut tryptophan metabolism under the probiotic treatment, such as changes in alpha diversity, tryptophan, and indoles derivatives. ConclusionB. breve CCFM1025 is a promising candidate psychobiotic strain that attenuates depression and associated gastrointestinal disorders. The mechanisms may be relevant to the changes in the gut microbiome and tryptophan metabolism. These findings support the future clinical applications of psychobiotics in the treatment of psychiatric disorders.

Bis(Tryptophan) Amphiphiles Form Ion Conducting Pores and Enhance Antimicrobial Activity against Resistant Bacteria.

The compounds referred to as bis(tryptophan)s (BTs) have shown activity as antimicrobials. The hypothesis that the activity of these novel amphiphiles results from insertion in bilayer membranes and transport of cations is supported by planar bilayer voltage-clamp studies reported herein. In addition, fluorescence studies of propidium iodide penetration of vital bacteria confirmed enhanced permeability. It was also found that BTs having either meta-phenylene or n-dodecylene linkers function as effective adjuvants to enhance the properties of FDA-approved antimicrobials against organisms such as S. aureus. In one example, a BT-mediated synergistic effect enhanced the potency of norfloxacin against S. aureus by 128-fold. In order to determine if related compounds in which tryptophan was replaced by other common amino acids (H2N-Aaa-linker-Aaa-NH2) we active, a family of analogs have been prepared, characterized, and tested as controls for both antimicrobial activity and as adjuvants for other antimicrobials against both Gram-negative and Gram-positive bacteria. The most active of the compounds surveyed remain the bis(tryptophan) derivatives.

Transition-Metal-Free Access to 2-Subsituted Indolines from Indoles via Dearomative Nucleophilic Addition Using Two-Molecule Organic Photoredox Catalysts

A Photoinduced dearomative nucleophilic addition to N-Boc indoles mediated by two-molecule organic photoredox catalysts such as phenanthrene and 1,4-dicyanobenzene with UV irradiation furnished 2-substituted indolines in moderate to quantitative yields. Hydroxide, alkoxide, and cyanide ions can be used as a nucleophile to provide 2-hydroxy, 2-alkoxy, and 2-cyanoindolines, respectively. Both electron-rich and -deficient indoles, including tryptophan derivatives, can be employed in the photoreaction to provide various indolines. This method provides transition-metal-free access to 2-subsituted indolines from indoles using organic photoredox catalysts under mild conditions.

Mycetoindole, an N-acyl dehydrotryptophan with plant growth inhibitory activity from an actinomycete of the genus Actinomycetospora.

A rare actinomycetal strain of the genus Actinomycetospora was found to produce a new tryptophan derivative, designated mycetoindole (1). The structure of 1 was determined to be N-3-methylcrotonoyl (Z)-dehydrotryptophan by NMR and MS analytical methods. Compound 1 reduced the root growth of lettuce Lactuca sativa seedlings at concentrations above 0.1 μM and almost completely inhibited seed germination at 10 μM.

Potential Anti-Alzheimer Agents from Guanidinyl Tryptophan Derivatives with Activities of Membrane Adhesion and Conformational Transition Inhibitions.

Guanidinyl tryptophan derivatives TGN1, TGN2, TGN3, and TGN4 were synthesized, and these compounds were shown to possess in vitro inhibitory activity for amyloid aggregation in a previous study. Nevertheless, the influence of the TGN series of compounds on the binding and permeation behaviors of an Aβ monomer to the cell membranes was not elucidated. In this study, we investigated the effect of compounds in the TGN series on the behavior of an Aβ monomer regarding its toxicity toward the bilayer lipid membrane using molecular dynamics (MD) simulation. MD simulations suggest that TGN4 is a potential agent that can interfere with the movement of the Aβ monomer into the membrane. The MM-GBSA result demonstrated that TGN4 exhibits the highest affinity to the Aβ1–42 monomer but has the lowest affinity to the bilayer. Moreover, TGN4 also contributes to a decrease in the binding affinity between the Aβ1–42 monomer and the POPC membrane. Regarding the results of the binding mode and conformational analyses, a high number of amino-acid residues were shown to provide the binding interactions between TGN4 and the Aβ1–42 monomer. TGN4 also reduces the conformational transition of the Aβ1–42 monomer by means of interacting with the monomer. The present study presents molecular-level insights into how the TGN series of compounds affect the membrane adsorption and the conformational transition of the Aβ1–42 monomer, which could be valuable for the further development of new anti-Alzheimer agents.

Site-Selective C–H Functionalization of Tryptophan Derivatives

Site-Selective C–H Functionalization of Tryptophan Derivatives

Double Arylation of the Indole Side Chain of Tri- and Tetrapodal Tryptophan Derivatives Renders Highly Potent HIV-1 and EV-A71 Entry Inhibitors†.

We have recently described a new generation of potent human immunodeficiency virus (HIV) and EV-A71 entry inhibitors. The prototypes contain three or four tryptophan (Trp) residues bearing an isophthalic acid moiety at the C2 position of each side-chain indole ring. This work is now extended by both shifting the position of the isophthalic acid to C7 and synthesizing doubly arylated C2/C7 derivatives. The most potent derivative (50% effective concentration (EC50) HIV-1, 6 nM; EC50 EV-A71, 40 nM), 33 (AL-518), is a C2/C7 doubly arylated tetrapodal compound. Its superior anti-HIV potency with respect to the previous C2-arylated prototype is in consonance with its higher affinity for the viral gp120. 33 (AL-518) showed comparable antiviral activities against X4 and R5 HIV-1 strains and seems to interact with the tip and base of the gp120 V3 loop. Taken together, these findings support the interest in 33 (AL-518) as a useful new prototype for anti-HIV/EV71 drug development.

Alkaloids and phenolics identification in fruit of Nitraria tangutorum Bobr. by UPLC-Q-TOF-MS/MS and their a-glucosidase inhibitory effects in vivo and in vitro

Nitraria tangutorum Bobr. (NTB), mainly distributed in the Qaidam Basin of Tibetan Plateau, have high economic, ecological and medicinal value. The chemical compositions in the NTB fruits were tentatively analyzed and characterized by applying UPLC-Q-TOF-MS/MS. Total 45 constituents, including 9 hydroxycinnamic acids derivatives, 12 flavonols, 4 flavonoids, 1 trolox derivative, 8 β-carboline alkaloids, 4 tryptophan derivatives, and 7 other amino acid derivatives were identified by comparing with standard products, and analyzing their retention times, characteristic fragment ions and deprotonated molecule ions. The activity studies in vitro indicated that NTB-Z and NTB-C extracts had marked inhibitory effects against sucrase and maltase. Further sucrose/maltose/starch tolerance experiment demonstrated that both NTB-Z and NTB-C extracts at 400 mg/kg could markedly lower the postprandial blood glucose (PBG) level in diabetic animals. All these results indicated that the NTB fruits could be used as the functional health food or medicine for controlling postprandial blood glucose level.

Influence of pH on radical reactions between kynurenic acid and amino acids tryptophan and tyrosine. Part I. Amino acids in free state

In the human eye lens the endogenous chromophores of UV-A light (315–400 nm) are able to sensitize radical reactions leading to protein modifications during normal aging and the cataract progression. Kynurenic acid (KNA−) is the most photochemically active dye of the human eye lens reported to date with pKa(KNAH2•) 5.5 for its radical form. Cataract is thought to develop under oxidative stress which could be accompanied by acidosis, an acidification of the intracellular environment. Protonation of kynurenyl radicals at mildly acidic conditions may change the outcome of radical reactions leading to additional damage to proteins. In this work we investigated the influence of pH on the degradation of initial reagents and the formation of products in photoinduced radical reactions between KNA− and amino acids tryptophan (Trp) and tyrosine (Tyr) in free states. Our results have shown that pH variation has minor influence on kinetics of reagent decay and accumulation of products in reactions between tyrosyl and kynurenic acid radicals. However in the case of Trp a two-fold decrease of the reagent degradation without visible changes in the composition of formed products was observed with pH decrease from 7 to 3. Time-resolved measurements have shown similar acidification-induced two-fold acceleration of decay of kynurenyl and tryptophanyl radicals via Back Electron Transfer (BET) with the restoration of initial reagents. Experiments with tryptophan derivatives with different pKa values for their radical forms point out the protonation of tryptophanyl radical as the driving force for BET acceleration at low pH. Our results demonstrate that the protonation of kynurenyl radical does not change its reactivity towards amino acids radicals but the total yield of radical photodamage decreases with the protonation of tryptophanyl radicals. It could be expected that radical induced damage to proteins will depend on the pKa of tryptophanyl radicals within a protein globule.

Conversion of l‐Tryptophan Derivatives into Biologically Active Amino Acid Ionic Liquids

AbstractNatural auxins are a group of plant hormones that affect plant growth and development. The most common auxin is indole‐3‐acetic acid (IAA), which is mainly synthesized from tryptophan. Since converting synthetic auxins into an ionic liquid increases their herbicidal activity, an attempt was made to synthesize new amino acid ionic liquids (AAILs) with l‐tryptophanate anions. As a result of the synthesis, two homologous series, tetraalkylammonium l‐tryptophanates and dialkyldimethylammonium l‐tryptophanates, were obtained with yields exceeding 95 %. For the obtained AAILs, basic physicochemical properties (solubility in solvents of different polarity, thermal stability, phase changes, and surface activity) were determined, and whether the obtained salts act as growth stimulants for lettuce (Lactuca sativa L.) was evaluated. The transformation of l‐tryptophan into AAILs improved the physicochemical properties and increased the auxin activity. In addition, the higher content of nutrients (micro‐ and macroelements) made lettuce a healthier food product.

Direct C4-Acetoxylation of Tryptophan and Tryptophan-Containing Peptides via Palladium(II)-Catalyzed C-H Activation.

An efficient regioselective palladium(II)-catalyzed C(sp2)-H 4-acetoxylation of tryptophan and tryptophan-containing peptides is described. This transformation achieves the direct construction of C-O bonds at the tryptophan C4-position and features good functional group tolerance. The 4-hydroxyl compound was obtained by removing acetyl after C4-acetoxylation of tryptophan derivatives and tryptophan-containing dipeptides. This method provides a novel strategy for the synthesis of 4-substituted tryptophan derivatives and modification of tryptophan-containing peptides.