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Search for "protein" in Full Text gives 691 result(s) in Beilstein Journal of Organic Chemistry. Showing first 200.
Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization
Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66
- essential domains, namely adenylation (A), condensation (C), and peptidyl carrier protein (PCP). Each type I PKS module consists of three core domains containing acyltransferase (AT), ketosynthase (KS), and acyl carrier protein (ACP). PCP and ACP are collectively called thiolation domain (T). The sequence
- chemically synthetic mimics before developing the enzymatic transformation. Due to N-acetylcysteamine (NAC) having a substructure to the phosphopantetheinyl arm of the carrier protein [24][25], the corresponding thioester can be recognized by TE domains and has become the most common substrate in enzymatic
- gramicidin S synthetase GrsB [44]. Combined with the peptidyl carrier protein, GrsB PCP-TE was tested by using corresponding pentapeptides NAC thioester and thiophenol thioester, which led to the formation of the desired cyclic decapeptide lactam gramicidin S (9) through a sequential dimerization and
New variochelins from soil-isolated Variovorax sp. H002
Beilstein J. Org. Chem. 2024, 20, 692–700, doi:10.3762/bjoc.20.63
- , we also identified a var gene cluster containing NRPS and PKS genes: the domain organizations of NRPS and PKS, and the adjacently encoded modification enzymes, were comparable to those of the gene cluster reported by Nett et al. with 92–99% identity at the protein level [5] (Figure 3a and Figure S42
- by diamonds. EIMS of DMOX derivatized free fatty acids derived from variochelins C–E (3–5). (a) 3, (b) 4, and (c) 5. (a) Plausible biosynthetic pathway of variochelin A–E (1–5). The circles represent domains: A: adenylation domain, C: condensation domain, PCP: peptide carrier protein, E
Production of non-natural 5-methylorsellinate-derived meroterpenoids in Aspergillus oryzae
Beilstein J. Org. Chem. 2024, 20, 638–644, doi:10.3762/bjoc.20.56
- adrI used in this study was constructed in our previous study, in which the product of AdrI was clearly detected [21], the inability of AdrI to yield a cyclized product is not likely to be caused by an inactive protein. The trt1-transformed strain produced a new compound 3 (molecular formula: C25H36O5
Introduction of a human- and keyboard-friendly N-glycan nomenclature
Beilstein J. Org. Chem. 2024, 20, 607–620, doi:10.3762/bjoc.20.53
- greatly facilitate keyboard-based mining for glycan substructures in glycan repositories. Keywords: N-glycans; nomenclature; structural features; Introduction Virtually any article on protein glycosylation starts with imposing assurances about the biological significance of the various structures. This
- the chemical peculiarities deliberately introduced by their sorcery. Biochemists and medical chemists, however, rather focus on the native glycan structure as grafted on the protein substrate by the biosynthetic machinery. Thus, biochemists could do with the much simpler IUPAC code [1] (Figure 1
- “proglycan” nomenclature, an acronym derived from our then nom de guerre “protein-glycosylation analysis” group. By the way, glycan analysis also funneled in activities in the area of allergy diagnosis, where the term MUXF3 enjoys widespread use [38][39][40]. Finally, our work on the isomer-specific analysis
Chemical and biosynthetic potential of Penicillium shentong XL-F41
Beilstein J. Org. Chem. 2024, 20, 597–606, doi:10.3762/bjoc.20.52
- reverse prenylated tryptophan. However, attempts to express the protein in various Escherichia coli hosts were unsuccessful, suggesting that eukaryotic hosts might be more suitable for future studies. We plan to conduct further experiments to substantiate the hypothesis regarding the biosynthetic pathways
A myo-inositol dehydrogenase involved in aminocyclitol biosynthesis of hygromycin A
Beilstein J. Org. Chem. 2024, 20, 589–596, doi:10.3762/bjoc.20.51
- the individual enzyme activities is lacking. In this study, we verify the activity for one enzyme in this pathway. We show that Hyg17 is a myo-inositol dehydrogenase that has a unique substrate scope when compared to other myo-inositol dehydrogenases. Furthermore, we analyze sequences from the protein
- family containing Hyg17 and discuss genome mining strategies that target this protein family to identify biosynthetic clusters for natural product discovery. Keywords: aminocyclitol; biosynthesis; hygromycin A; inositol dehydrogenase; myo-inositol; Introduction Hygromycin A is a natural product that
- bodies when recombinantly produced by various E. coli expression strains. However, we were able to obtain pure soluble protein when expressing Hyg17 in a Rhodococcus expression system (Supporting Information File 1, Figure S1) [10][11]. According to the proposed hygromycin A biosynthetic pathway, Hyg17
Possible bi-stable structures of pyrenebutanoic acid-linked protein molecules adsorbed on graphene: theoretical study
Beilstein J. Org. Chem. 2024, 20, 570–577, doi:10.3762/bjoc.20.49
- Yasuhiro Oishi Motoharu Kitatani Koichi Kusakabe Graduate School of Science, University of Hyogo, Kamigori, Hyogo 678-1297, Japan 10.3762/bjoc.20.49 Abstract We theoretically analyze possible multiple conformations of protein molecules immobilized by 1-pyrenebutanoic acid succinimidyl ester (PASE
- ) linkers on graphene. The activation barrier between two bi-stable conformations exhibited by PASE is confirmed to be based on the steric hindrance effect between a hydrogen on the pyrene group and a hydrogen on the alkyl group of this molecule. Even after the protein is supplemented, this steric hindrance
- effect remains if the local structure of the linker consisting of an alkyl group and a pyrene group is maintained. Therefore, it is likely that the kinetic behavior of a protein immobilized with a single PASE linker exhibits an activation barrier-type energy surface between the bi-stable conformations on
Entry to new spiroheterocycles via tandem Rh(II)-catalyzed O–H insertion/base-promoted cyclization involving diazoarylidene succinimides
Beilstein J. Org. Chem. 2024, 20, 561–569, doi:10.3762/bjoc.20.48
- modern drug design [1][2]. They are known to promote higher success rates, when targeting three-dimensional protein molecules [3][4]. Furthermore, a wide variety of spirocyclic fragments can be spotted in natural products [5]. The aspects mentioned unveil the development of synthetic methodologies
- ], drospirenone (exhibits high affinity to progesterone receptors and is used as a birth control medication) [26][27], griseofulvin (an antifungal agent used to treat fungal infections of the fingernails and toes) [28], as well as oliceridine (a selective G protein-biased μ-opioid receptor agonist used for
Synthesis and biological profile of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a novel class of acyl-ACP thioesterase inhibitors
Beilstein J. Org. Chem. 2024, 20, 540–551, doi:10.3762/bjoc.20.46
- with emphasis on the structural diversity of small-molecule ligands. In this context, acyl-acyl carrier protein (acyl-ACP) thioesterase inhibitors have shown a remarkable variability. Fatty acid thioesterase (FAT) enzymes represent a family of proteins exclusively found in higher plants. They mediate
- binding affinity to enzyme targets, e.g., acyl-ACP thioesterases, belonging to the protein family of FATs, was demonstrated by using co-crystallization, fluorescence-based thermal shift assays, and chemoproteomics techniques [3]. Likewise, methiozolin (2) is a recently assigned FAT inhibitor that has
- A protein was expressed in E. coli BL21Star(DE3) cells. 5 mL of an overnight culture of E. coli cells grown in LB medium with 100 µg/mL carbenicillin were used to inoculate 0.5 L of autoinduction medium containing 100 µg/mL carbenicillin [28]. The bacteria were grown at 37 °C and 120 rpm for about
Switchable molecular tweezers: design and applications
Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45
Development of a chemical scaffold for inhibiting nonribosomal peptide synthetases in live bacterial cells
Beilstein J. Org. Chem. 2024, 20, 445–451, doi:10.3762/bjoc.20.39
- arm in an adjacent peptidyl carrier protein (PCP). The amino acid loaded on the PCP then undergoes coupling with the amino acid loaded on the downstream PCP in the condensation (C) domain. Finally, the linear peptide on the PCP in the last module is either hydrolyzed or cyclized by a thioesterase (TE
- differences in the composition of cell membranes and presence of efflux pumps [9]. Specific protein labeling using a chemical probe can help to identify, characterize, and visualize target proteins [10][11]. The first chemical probe used for A-domains in NRPSs was reported by Marahiel et al. [8]. They
- previously described an activity-based protein profiling (ABPP) strategy for NRPSs using ABPs that target A-domains (Figure 2b) [13][14][15]. The probes comprise an aminoacyl-AMS ligand and a photoaffinity group with clickable alkyne functionality appended to the 2′-OH group of adenosine. A complex structure
Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles
Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36
- cruciferous vegetables, as hydrolysis products from the metabolism of glucosinolates [1]. In 2017, Müller and her research team showcased the ability of BIMs to operate as anti-inflammatory drugs by acting as GPR84 agonists [2]. GPR84 is a protein-coupled receptor found in immune cells, which regulates a
- related environments [8]. The mechanism of action involves the binding of BIMs to the penicillin-restricting protein PBP2a which inhibits the biosynthesis of the bacterial cell wall, making the treatment feasible without any toxicity to human cells [9][10]. The applications of BIMs have also been extended
Discovery of unguisin J, a new cyclic peptide from Aspergillus heteromorphus CBS 117.55, and phylogeny-based bioinformatic analysis of UngA NRPS domains
Beilstein J. Org. Chem. 2024, 20, 321–330, doi:10.3762/bjoc.20.32
- genome was initially screened using fungiSMASH to identify scaffolds/contigs encoding secondary metabolites. Scaffold MSFL01000005.1 was further investigated using FGENESH [17] to further refine gene boundaries, introns, and resulting protein sequence (Table S1, Supporting Information File 1
Elucidating the glycan-binding specificity and structure of Cucumis melo agglutinin, a new R-type lectin
Beilstein J. Org. Chem. 2024, 20, 306–320, doi:10.3762/bjoc.20.31
- member of characterized melon lectins, namely the Cucumis melo agglutinin (CMA1), an R-type lectin derived from melon. Prior to our study, CMA1 was only a predicted protein from genomic sequencing, with moderate certainty scores on lectin-specific databases. Our comprehensive analysis using glycan array
- unique binding profile of specifically recognizing C2-substituted galactose in the context of glycans. Results and Discussion Identification and production of a new lectin from the melon Cucumis melo CMA1 is a predicted protein from whole-genome shotgun sequencing of leaves from the melon plant Cucumis
- , as an archetypal example of melon lectins. For this, we needed to express the lectin recombinantly. As it is a secreted plant protein, we elected to express it in mammalian cell lines, to maximize the chances of a functional protein, because of post-translational modifications that would be lacking
Visible-light-induced radical cascade cyclization: a catalyst-free synthetic approach to trifluoromethylated heterocycles
Beilstein J. Org. Chem. 2024, 20, 118–124, doi:10.3762/bjoc.20.12
- compounds (Figure 1) [1][2][3], which exhibit a wide range of biological and pharmaceutical activities [4]. For example, mersicarpine has been found to inhibit protein translation and induce apoptosis [5] and vinburnine acts as a vasodilator for the treatment of cerebrovascular insufficiency [6][7]. Given
Identification of the p-coumaric acid biosynthetic gene cluster in Kutzneria albida: insights into the diazotization-dependent deamination pathway
Beilstein J. Org. Chem. 2024, 20, 1–11, doi:10.3762/bjoc.20.1
- recent studies [9][10][11][12][13][14]. Most of them belong to the adenylate-forming enzyme superfamily (ANL superfamily) and utilize ATP to activate nitrous acid by AMPylation, with the only exception being AzpL in alazopeptin biosynthesis, which is a membrane protein that catalyzes diazotization
- biosynthetic pathway [13]. In this pathway, 3-amino-4-hydroxybenzoic acid (3,4-AHBA, 1), synthesized by AvaH and AvaI, is loaded onto AvaA3 (carrier protein) by AvaA1 (AMP-dependent ligase), resulting in 3,4-AHBA-AvaA3. A highly reducing type II polyketide synthase (PKS) system [15][16] (AvaA2, A4, A5, and A8
- insights into how highly reducing type II PKSs control starter substrate incorporation. The only difference between avenalumic acid and p-coumaric acid is the chain length. The CLF CmaA5 shows 35.4% identity to AvaA5, which is the lowest similarity score among Ava and Cma protein pairs (Table 1). This is
Long oligodeoxynucleotides: chemical synthesis, isolation via catching-by-polymerization, verification via sequencing, and gene expression demonstration
Beilstein J. Org. Chem. 2023, 19, 1957–1965, doi:10.3762/bjoc.19.146
- ligation from shorter 20 to 60 nt ODNs produced by automated de novo chemical synthesis. While these methods have made many projects in areas such as synthetic biology and protein engineering possible, they have various drawbacks. For example, they cannot produce genes and genomes with long repeats and
- 401 nt ODNs were synthesized and purified with CBP. The two were joined together using Gibson assembly to give the 800 nt green fluorescent protein (GFP) gene construct. The sequence of the construct was verified via Sanger sequencing. To demonstrate the potential use of the long ODN synthesis method
- . Keywords: automated synthesis; catching-by-polymerization; gene assembly; long oligonucleotide; synthetic biology; Introduction Long oligodeoxynucleotides (ODNs) are segments of DNAs extending beyond one hundred nucleotides (nt). Emerging research areas such as synthetic biology [1][2], protein
Studying specificity in protein–glycosaminoglycan recognition with umbrella sampling
Beilstein J. Org. Chem. 2023, 19, 1933–1946, doi:10.3762/bjoc.19.144
- proteins. The structural and functional heterogeneities of GAGs as well as their ability to bind specific proteins are determined by the sugar composition of the GAG, the size of the GAG chains, and the degree and pattern of sulfation. A deep understanding of the interactions in protein–GAG complexes is
- GAG properties, especially protein recognition specificity and multipose binding. We found that the binding free energy landscape in the proximity of the GAG native binding pose is complex and implies the co-existence of several binding poses. The sliding of a GAG chain along a protein surface could
- be a potential mechanism of GAG particular sequence recognition by proteins. Keywords: glycosaminoglycan; molecular docking; protein–glycosaminoglycan interaction specificity; RS-REMD; umbrella sampling; Introduction Glycosaminoglycans (GAGs) are long linear periodic anionic polydisperse
N-Boc-α-diazo glutarimide as efficient reagent for assembling N-heterocycle-glutarimide diads via Rh(II)-catalyzed N–H insertion reaction
Beilstein J. Org. Chem. 2023, 19, 1841–1848, doi:10.3762/bjoc.19.136
- ; Introduction Targeted protein degradation (TPD) has transformed the field of drug discovery [1][2]. Utilizing proximity-induced pharmacological strategies [3], this method has fostered the creation of numerous molecular glues and proteolysis-targeting chimeras (PROTACs). By manipulation of the internal
GlAIcomics: a deep neural network classifier for spectroscopy-augmented mass spectrometric glycans data
Beilstein J. Org. Chem. 2023, 19, 1825–1831, doi:10.3762/bjoc.19.134
- intelligence in combination with spectroscopy-augmented mass spectrometry for carbohydrates sequencing and glycomics applications. Keywords: Bayesian neural network; deep learning; glycomics; IR; spectroscopy; Introduction DNA and protein sequencing technologies that aim at determining the structure of a
Effects of the aldehyde-derived ring substituent on the properties of two new bioinspired trimethoxybenzoylhydrazones: methyl vs nitro groups
Beilstein J. Org. Chem. 2023, 19, 1713–1727, doi:10.3762/bjoc.19.125
- first to establish the suitability of N-acylhydrazones as novel metallophores able to affect protein aggregation and/or oxidation enhanced by physiological metal–protein anomalous interactions related to Alzheimer's (AD) and Parkinson's (PD), as well as to prion diseases [27][28][29][30][31][32][33][34
Sulfur-containing spiroketals from Breynia disticha and evaluations of their anti-inflammatory effect
Beilstein J. Org. Chem. 2023, 19, 1604–1614, doi:10.3762/bjoc.19.117
- -stimulated increase in IL-1β and IL-6 production was suppressed by compound 7 at a concentration of 10 μM (Figure 6f and 6g). Thus, compound 7 inhibited LPS-stimulated IL-1β and IL-6 mRNA and protein expression in RAW 264.7 cells. Although confirmed only at the mRNA level, 1, 2, and 6 likely exhibit similar
Synthesis and biological evaluation of Argemone mexicana-inspired antimicrobials
Beilstein J. Org. Chem. 2023, 19, 1511–1524, doi:10.3762/bjoc.19.108
- often attributed to high binding affinity to DNA, interference with protein biosynthesis, induction of membrane leakage, and affecting GTPase activity in bacteria cell division [12][13][14][15]. Recent reports have also pointed to inhibition of the ‘filamenting temperature-sensitive mutant Z’ (FtsZ
- ) protein [16][17], as well as perturbing carbohydrate metabolism to generate reactive oxygen species that damage the DNA [18], as modes of action for berberine’s antibacterial effects. The antitumor properties of berberine have been attributed to DNA binding, and in particular regulating the activity of
- ]. Similar to berberine, results have demonstrated that the antibacterial activity of chelerythrine can be tied to DNA intercalation and disruption to cell membrane permeability [11][24]. One particular mechanism of action noted for chelerythrine’s antitumor bioactivity is through the inhibition of protein
Functions of enzyme domains in 2-methylisoborneol biosynthesis and enzymatic synthesis of non-natural analogs
Beilstein J. Org. Chem. 2023, 19, 1452–1459, doi:10.3762/bjoc.19.104
- studied. Several 2-methylisoborneol synthases have a proline-rich N-terminal domain of unknown function. The results presented here demonstrate that this domain leads to a reduced enzyme activity, in addition to its ability to increase long-term solubility of the protein. Furthermore, the substrate scope
- elution buffer used for protein purification through Ni2+-NTA affinity chromatography. While domain B alone showed a substantial enzyme precipitation after 12 h at 4 °C, full length 2MIBS did not (Figure 1B), suggesting that the A domain increases enzyme solubility and long-term stability. This effect
- needs a covalent bond between the two domains A and B, as indicated by a similar precipitation of domain B alone and domain B in the presence of domain A. In these experiments, the N-terminal His-tags at both domains A and B may influence protein–protein interaction with the consequence that the mixture
Functional characterisation of twelve terpene synthases from actinobacteria
Beilstein J. Org. Chem. 2023, 19, 1386–1398, doi:10.3762/bjoc.19.100
- Streptomyces cattleya that shows the same sequence deviation in the NSE triad and has 58% identity [49], and to phomopsene synthase from A. albata with 36% identity (Figure S43, Supporting Information File 1) [50]. The incubation of GPP, FPP and GFPP with the purified protein only resulted in acyclic products
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