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Search for "proteins" in Full Text gives 518 result(s) in Beilstein Journal of Organic Chemistry. Showing first 200.
Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies
Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261
- biomolecules like DNA and lipids. Lipid peroxidation and membrane disruption can cause random cross-linking, resulting in cell death and the fragmentation of proteins and enzymes. Elevated concentrations of reactive oxygen species (ROS) from various molecular processes contribute to the oxidation of proteins
Chemical structure metagenomics of microbial natural products: surveying nonribosomal peptides and beyond
Beilstein J. Org. Chem. 2024, 20, 3050–3060, doi:10.3762/bjoc.20.253
- product biosynthesis, along with all the information an organism needs, are encoded in its genome. Genetic information is transcribed and translated into proteins that carry out chemical reactions that sustain life, which include both primary metabolism and the biosynthesis of natural products. Direct
- protein sequencing by Edman degradation used to be standard practice in studying proteins but nowadays is rarely performed [39]. This is because the rules of transcription and translation are understood well enough for the sequence of a protein (its primary structure) to be predicted based on the
Tailored charge-neutral self-assembled L2Zn2 container for taming oxalate
Beilstein J. Org. Chem. 2024, 20, 3007–3015, doi:10.3762/bjoc.20.250
- ; metallocontainer; oxalate; Introduction Dicarboxylic acids and their corresponding anions are essential intermediates in the biosynthesis of proteins and important biological metabolites [1][2]. As a result, the development of receptors for this class of compounds is of high interest [3][4][5]. Oxalate, the
Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts
Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243
- with thiophene favored the formation of phenylated products as the major outcome. Additionally, mercaptoazoles were found to be compatible with this protocol, expanding its applicability to include these compounds. The functionalization of peptides and proteins plays a vital role in the development of
- functional entities. In 2021, Byrne et al. published an impressive report detailing a novel protocol for the chemoselective late-stage variation of proteins and peptides at cysteine residues 91 and 94 in an aqueous buffer in the presence of suitably functionalized diaryliodonium salts 92 and 95 (Scheme 38
- high conversions (83–93%) in 1–20 hours. Purification by HPLC yielded the isolated oxime conjugates in excellent amounts. This methodology presents a promising approach for the late-stage variation of proteins and peptides, offering versatility and efficiency in aqueous environments. In addition to
N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity
Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240
- viability and in induction of apoptosis [50]. The presence of this compound results in downregulation of the caspase antagonistic proteins c-FLIP and XIAP via caspase-8 and caspase-3 in the (extrinsic) apoptosis cascade. Similarly as discussed above for the activity of 3-alkylideneoxindole-N-glycosides
A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis
Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214
- )–H functionalization C–N coupling reaction by developing an electrochemical method for the bioconjugation of tyrosine in proteins/polypeptides with phenothiazine residues, achieving excellent site- and chemoselectivity (Scheme 4a). This method was inspired by an earlier work from the Gouin group
Tandem diazotization/cyclization approach for the synthesis of a fused 1,2,3-triazinone-furazan/furoxan heterocyclic system
Beilstein J. Org. Chem. 2024, 20, 2342–2348, doi:10.3762/bjoc.20.200
- products and pharmacologically active molecules. For example, nucleic acids, proteins and enzymes, hormones and vitamins, essential for the functioning of a living organism, also contain nitrogen frameworks [1][2]. Besides that, nitrogen-containing compounds are widely used in medicine as antibiotics
Improved deconvolution of natural products’ protein targets using diagnostic ions from chemical proteomics linkers
Beilstein J. Org. Chem. 2024, 20, 2323–2341, doi:10.3762/bjoc.20.199
- Andreas Wiest Pavel Kielkowski LMU Munich, Department of Chemistry, Butenandtstr. 5-13, 81377 Munich, Germany 10.3762/bjoc.20.199 Abstract Identification of interactions between proteins and natural products or similar active small molecules is crucial for understanding of their mechanism of
- action on a molecular level. To search elusive, often labile, and low-abundant conjugates between proteins and active compounds, chemical proteomics introduces a feasible strategy that allows to enrich and detect these conjugates. Recent advances in mass spectrometry techniques and search algorithms
- identification rates and may help to identify otherwise difficult to find interactions between active compounds and proteins, which may result from unperturbed conditions, and thus are of high physiological relevance. Keywords: chemical proteomics; diagnostic ions; mass spectrometry; target identification
Cell-free protein synthesis with technical additives – expanding the parameter space of in vitro gene expression
Beilstein J. Org. Chem. 2024, 20, 2242–2253, doi:10.3762/bjoc.20.192
- osmolarity using ten different technical additives including organic solvents, polymers, and salts. It is shown that the synthesis of two model proteins, namely superfolder GFP (sfGFP) and the enzyme truncated human cyclic GMP-AMP synthase fused to sfGFP (thscGAS-sfGFP), is very robust against most of the
- biocatalysts [1][2]. The open environment allows easy manipulation of the protein synthesis [3] and coupling to subsequent enzyme activity assays, e.g., for substrate screening [4][5]. The CFPS system is advantageous for proteins that are difficult to express in a viable host cell, e.g., due to toxic effects
- of the intracellular environment on the function and cellular behavior of proteins are composition, viscosity, and macromolecular crowding [16], these parameters could have a strong impact on the protein synthesis performance using CFPS. For example, the addition of chemical chaperones, such as
Computational toolbox for the analysis of protein–glycan interactions
Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180
- , both in free state and in complex with proteins, also with reference to the principles, methodologies, and applications of all-atom molecular dynamics simulations. Herein, we focused on the programs that are generally employed for preparing protein and glycan input files to execute molecular dynamics
- , proteins, and nucleic acids. In humans and animals, they form the so-called glycocalyx, a protecting sugar coat decorating the cell surface and modulating a myriad of cell–cell interactions [1]. It is composed of branched or elongated glycan chains covalently linked to proteins or lipids, hereby
- interaction with host proteins [5][6]. Notably, the complexity of the glycome far surpasses that of the genome, transcriptome, and proteome, not only due to the structural and conformational diversity of glycans, whose synthesis is not template driven, but also due to their dynamic nature [5][6]. Although
Negishi-coupling-enabled synthesis of α-heteroaryl-α-amino acid building blocks for DNA-encoded chemical library applications
Beilstein J. Org. Chem. 2024, 20, 1922–1932, doi:10.3762/bjoc.20.168
- Matteo Gasparetto Balazs Fodi Gellert Sipos X-Chem Zrt., Záhony u. 7, DA Building, Graphisoft Park, Budapest, 1031, Hungary 10.3762/bjoc.20.168 Abstract Amino acids are vital motifs in the domain of biochemistry, serving as the foundational unit for peptides and proteins, while also holding a
- bifunctional building blocks (BBs) can quickly increase the diversity of these molecular libraries [6]. Hence, DEL practitioners constantly seek access to novel building blocks [7]. Amino acids (AAs) are vital motifs in the domain of biochemistry, serving as the foundational unit for peptides and proteins
The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)
Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162
Hetero-polycyclic aromatic systems: A data-driven investigation of structure–property relationships
Beilstein J. Org. Chem. 2024, 20, 1817–1830, doi:10.3762/bjoc.20.160
- prevalent classes of molecules known to humankind; indeed, it is estimated that two-thirds of known molecules contain (or are themselves) an aromatic moiety [1]. In addition to their presence in naturally occurring molecules, such as DNA and proteins, they have also been harnessed for various uses, ranging
Discovery of antimicrobial peptides clostrisin and cellulosin from Clostridium: insights into their structures, co-localized biosynthetic gene clusters, and antibiotic activity
Beilstein J. Org. Chem. 2024, 20, 1800–1816, doi:10.3762/bjoc.20.159
- ) containing class II lanthipeptide synthetases encoded by lanM genes. A phylogenetic study analyzing homologous sequences of functional LanM sequences revealed a unique evolutionary clade of 17 LanM proteins associated with 12 Clostridium bacterial genomes. In silico exploration identified nine complete BGCs
- . While some strains exhibit resistance due to changes in the cell wall, biofilm formation, or the expression of resistance proteins such as ABC transporters or proteases [28], specific mutations in nisin have rendered previously resistant strains susceptible [29]. The structural diversity of these
- part of the biosynthetic machinery for the production of ruminococcin A [41] and Flv peptides [42] from the clostridial class. As a result, 315 homologous proteins were identified and included in the comparative phylogenetic study. A phylogenetic tree was built (Figure 1) with the reference LanM
Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations
Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151
- fractionated cell cultures of M. alba with 49 was followed by irradiation with 365 nm light to generate reactive carbene from diazirine. This sequence allowed the formation of covalent bonds between the synthetic probe and binding proteins. The resulting mixture was subjected to a copper-catalyzed click
- reaction with biotin azide, which led to selective pull-down with streptavidin agarose and isolation of the probe–protein covalent complex. Proteomic analysis of the isolated proteins narrowed down the MaMO and MaDA candidates, including several berberine bridge enzyme (BBE)-like enzymes. This FAD-linked
- oxidase family is known to catalyze a variety of oxidative transformations critical for natural products biosynthesis [55]. Further transcriptome analysis of the candidate proteins led to the identification of two BBE-like enzymes, MaMO and MaDA, as key biosynthetic enzymes for 3. These enzymes were
Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry
Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147
- proteins allows peptides to disturb protein–protein interactions, which is a challenging task for small molecules. The principles of RiPP biosynthesis make the RiPP technology an ideal platform for the generation of designed peptides and allow tailored derivatisation of these peptides. The RiPP technology
- analogues [48][49][50][51][52]. The PURE system is a well-established method for rapidly expressing functional proteins. However, synthesising peptides with unnatural amino acids remains a labour-intensive process. tRNAs charged with unnatural or modified amino acids cannot be easily replenished within the
- system and must be prepared beforehand. The incorporation of unnatural amino acids by the ribosome is less efficient and leads to incomplete translation, resulting in shunt products. Additionally, ribosome recycling efficiency and synthesis of full length proteins declines with length of the primary
Polymer degrading marine Microbulbifer bacteria: an un(der)utilized source of chemical and biocatalytic novelty
Beilstein J. Org. Chem. 2024, 20, 1635–1651, doi:10.3762/bjoc.20.146
- [48]. The three-dimensional structure of CEST revealed that it belongs to the α/β-class of proteins consisting of a central six-stranded β-sheet flanked by eight α-helices. Site-directed mutagenesis indicated that a Ser-His-Glu catalytic triad was essential for the enzyme activity [48]. Another cold
Regio- and stereochemical stability induced by anomeric and gauche effects in difluorinated pyrrolidines
Beilstein J. Org. Chem. 2024, 20, 1572–1579, doi:10.3762/bjoc.20.140
- of the pyrrolidine ring in proline motifs has been found to induce significant conformational changes that impact the structure and biological roles of modified peptides and proteins. Vicinal difluorination of fluoroproline, for example, in (3S,4R)-3,4-difluoroproline, serves to mitigate the inherent
- pervade biochemistry in peptides and proteins. The chemical and biological properties of substituted pyrrolidine derivatives, along with many other compounds, hinge on the relative stereochemistry. It is well established that the presence of fluorine in an organic molecule can significantly influence the
- conformational stability of proline-rich proteins such as collagen [2]. Therefore, pyrrolidine derivatives are particularly susceptible to conformational control induced by a fluorine substituent. The 5-membered pyrrolidine ring is a cyclic alkylamine that adopts a conformation that resembles the familiar
Mining raw plant transcriptomic data for new cyclopeptide alkaloids
Beilstein J. Org. Chem. 2024, 20, 1548–1559, doi:10.3762/bjoc.20.138
- (Figure 1). Recent enzymatic reconstitution has demonstrated that the burpitide cyclases can function either autocatalytically (fused) or as traditional stand-alone proteins with separate free peptide substrates (split) [4][7][8][9][10][11]. When fully matured, burpitides possess a wide range of
- base pairs (Figure 6B). While the proposed gene cluster is missing a potential peptidase, it contains all the other proteins necessary for the biosynthesis of GJA649 and the other putative G. jasminoides cyclopeptide alkaloids. New cyclopeptide alkaloids in Alternanthera bettzickiana Based on the
Photoswitchable glycoligands targeting Pseudomonas aeruginosa LecA
Beilstein J. Org. Chem. 2024, 20, 1486–1496, doi:10.3762/bjoc.20.132
- bacterial infections occur by adhesion to host tissues through receptor–ligand interaction between bacterial carbohydrate-binding proteins (lectins) and oligosaccharides at the host cell surface. Pseudomonas aeruginosa (PA), a Gram-negative, opportunistic and ubiquitous environmental bacterium, is known as
Cofactor-independent C–C bond cleavage reactions catalyzed by the AlpJ family of oxygenases in atypical angucycline biosynthesis
Beilstein J. Org. Chem. 2024, 20, 1198–1206, doi:10.3762/bjoc.20.102
- . Cofactor-independent oxidative ring cleavage and rearrangement reactions of CR1 (8) catalyzed by homologous proteins of AlpJ To extend the generality of our findings, we assessed the cofactor-independent catalytic capabilities of other homologous proteins of AlpJ. Previous investigations indicated that the
- -morpholino)propanesulfonic acid (MOPS) buffer (pH 7.5), and the cells were disrupted by ultrasonication to obtain the cell extract. Cell debris was removed by centrifugation (14,000g, 15 min). The proteins were purified by Ni-NTA agarose chromatography, desalted, and concentrated by centrifugation (8,000g
- -independent AlpJ-family oxygenases. Supporting Information Supporting Information File 44: Sequence comparison results and phylogenetic tree of AlpJ-family enzymes and anthrone oxygenases, crystal structures of AlpJ and ActVA-Orf6, SDS-PAGE of purified proteins, HPLC traces of prosthetic group identification
Novel analogues of a nonnucleoside SARS-CoV-2 RdRp inhibitor as potential antivirotics
Beilstein J. Org. Chem. 2024, 20, 1029–1036, doi:10.3762/bjoc.20.91
- directly act as a viral messenger RNA and encodes essential enzymes for replication [3]. Inhibiting these nonstructural proteins that are part of the replication complex has already shown great success in antiviral therapy [4][5][6][7]. The viral RNA-dependent RNA polymerase (RdRp) is encoded in all RNA
Activity assays of NnlA homologs suggest the natural product N-nitroglycine is degraded by diverse bacteria
Beilstein J. Org. Chem. 2024, 20, 830–840, doi:10.3762/bjoc.20.75
- contaminants but are either undissociated higher oligomer states or are oligomers whose formation is induced by SDS treatment, which has been observed for other proteins [29][30]. To characterize these oligomer states of native protein, analytical size exclusion chromatography data were collected (Figure 2B
- nm/A280 nm ratio for each homolog was greater than 1.0, consistent with high occupancy of heme incorporation in the proteins. Iron analyses of each of the homologs were consistent with this conclusion; the heme iron concentrations per protein were consistent with stoichiometric or nearly
- structure of oligomeric proteins [31]. The highest ranked model is shown in Figure 5. AlphaFold predicted a canonical α/β fold with high confidence, between residues Arg16 and Gly146 (Figure 5A). Structural clustering using Foldseek Cluster identified substantial similarities to other PAS domain proteins
Methodology for awakening the potential secondary metabolic capacity in actinomycetes
Beilstein J. Org. Chem. 2024, 20, 753–766, doi:10.3762/bjoc.20.69
- chaxalactins A–C (16–18), and polycyclic polyether natural products designated terrosamycins A and B (19, 20), respectively [55][56]. Thus, the OSMAC strategy has been successfully applied over the last 10 years to generate new secondary metabolites from a single microbial strain. Sensor proteins for medium
- structure. Saito et al. are now interested in determining how and why these HSMs are produced. First, when actinomycetes sense heat stress, repression mediated by heat shock sensor proteins such as HrcA, HspR, and RheA is released. The expression of various genes, such as those encoding heat shock proteins
- is regulated by such heat shock sensors. Although long-term high-temperature culture experiments are employed in this study, reactive oxygen species (ROS) may exert a stronger effect than high temperature. In actinomycetes, several sensor proteins for ROS have been reported (e.g., SoxR and OxyR
Research progress on the pharmacological activity, biosynthetic pathways, and biosynthesis of crocins
Beilstein J. Org. Chem. 2024, 20, 741–752, doi:10.3762/bjoc.20.68
- , and UGTs are the key players in crocin biosynthesis. Empowered by the genomic, transcriptomic, and metabolomic analysis and biochemical characterization, many such enzymes have been identified. Some proteins, exemplified by GjCCD4a and GjUGT94E13, exhibit broad substrate promiscuity and high catalytic
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