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Search for "peptide" in Full Text gives 465 result(s) in Beilstein Journal of Organic Chemistry. Showing first 200.
Asymmetric synthesis of fluorinated derivatives of aromatic and γ-branched amino acids via a chiral Ni(II) complex
Beilstein J. Org. Chem. 2025, 21, 659–669, doi:10.3762/bjoc.21.52
- amino acids. We synthesized two fluorinated analogs of phenylalanine, which are still unexplored in the context of peptide and protein chemistry. Furthermore, both diastereomers of trifluoroleucine were synthesized, demonstrating that the described strategy can also be applied to synthesize enantio‑ and
- -natural amino acids are pivotal in protein engineering and drug development. Over 30% of approved small‑molecule drugs today contain non‑canonical amino acid building blocks [1][2]. In peptide and protein engineering, non‑natural amino acids significantly increase the respective range of tools used to
- modify a series of peptide and protein-related properties such as stability, specificity, and folding. In this regard, fluorinated amino acids are particularly important. Incorporation of fluorinated groups into the sequence of peptides and proteins can, for instance, regulate the respective
Photocatalyzed elaboration of antibody-based bioconjugates
Beilstein J. Org. Chem. 2025, 21, 616–629, doi:10.3762/bjoc.21.49
- such methods are generally reported with a heterogeneous DAR, the group developed a site-specific approach leading to a homogeneous DAR 2, thanks to a photoreactive Fc-binding peptide derivative (pFcBP) containing a photoleucine (pLeu) [46]. By analyzing the X-ray crystal structure of IgG, the
- acts as a microtubule destabilizer. To ensure the stability and homogeneity of the final product, the design of the FcBP included a norbornene motif at the N-terminal end of the peptide sequence. The norbornene motif selectively reacts with a tetrazine located on the spacer-payload. This study
Formaldehyde surrogates in multicomponent reactions
Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45
- peptide carbonyl group. Both moieties result from the glyoxylate compound (Scheme 43). There are many examples in which the ester moiety opens the possibility of a further intramolecular cyclization with a nucleophile (for example, a protected amine in an Ugi/deprotection/cyclization sequence [98][99][100
Binding of tryptophan and tryptophan-containing peptides in water by a glucose naphtho crown ether
Beilstein J. Org. Chem. 2025, 21, 541–546, doi:10.3762/bjoc.21.42
- towards ʟ-Trp over its ᴅ-enantiomer (entries 1 and 6, Table 1). Since tryptophan fulfills many of its biological functions as a component of peptides and proteins [2][3][4][5], we also probed, if 1 can recognize tryptophan residues within peptide sequences. For this purpose, we prepared six model
- tripeptides 2–7 consisting of one tryptophan and two alanine residues. We varied the position of the tryptophan in the peptide sequence, N-terminus in 2, middle of the chain in 3, and C-terminus in 4 to check if this affects their binding by 1. To probe the importance of the N-terminal amino group in the
- , Table 2). The binding affinity of 1 towards peptide 4 is around 1.5 times higher than for the free amino acid (entry 3, Table 2). The acetylated analogues of peptides 2 and 3 – compounds 5 and 6, are bound by 1 notably weaker, with 1.8× and 1.3× lower affinities respectively (entries 4 and 5, Table 2
Synthesis of N-acetyl diazocine derivatives via cross-coupling reaction
Beilstein J. Org. Chem. 2025, 21, 490–499, doi:10.3762/bjoc.21.36
- accumulation in the environment after excretion [1][6][7]. These superior properties of diazocines have been exploited in several applications such as the control of protein folding by implementation as cross-linkers between protein side chains [8] or in peptide backbones [9], as photoswitchable
Antibiofilm and cytotoxic metabolites from the entomopathogenic fungus Samsoniella aurantia
Beilstein J. Org. Chem. 2025, 21, 327–339, doi:10.3762/bjoc.21.23
- previously reported study investigating the biosynthesis of tenellin from Beauveria bassiana CBS110.25 [13], it was established that tenellin and a vast array of related metabolites could be synthesized through a cascade involving hybrid highly reducing polyketide synthase–non-ribosomal peptide synthetase
Streamlined modular synthesis of saframycin substructure via copper-catalyzed three-component assembly and gold-promoted 6-endo cyclization
Beilstein J. Org. Chem. 2025, 21, 226–233, doi:10.3762/bjoc.21.14
- of saframycin A (1) is assembled from two molecules of ʟ-tyrosine derivative 5 and peptidyl aldehyde 6 by non-ribosomal peptide synthetases (NRPS, Scheme 1a) [15][16][17][18][19][20][21]. The pivotal NRPS module, SfmC, catalyzes iterative regio- and stereoselective Pictet–Spengler (PS)-type
Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations
Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12
- condensation of carboxylic acids with anilines, often promoted by activating agents such as thionyl chloride or peptide coupling agents [86][87][88][89]. However, these protocols rely on environmentally harmful reagents and produce unwanted byproduct wastes. Recently, the research group of Son showcased a
Recent advances in organocatalytic atroposelective reactions
Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6
- dehydration, release of the chiral acid, and aromatization through tautomerization of intermediate Int-50 generate the desired product 195. Kwon et al. compared the effectivity of traditional biaryl phosphoric acid C30 with peptide phosphoric acid C46 in the cyclodehydration of trifluorophenylaminoacetals
- present. On the other hand, peptide phosphoric acid C46 appears to work through an alternative mode of enantioinduction, where conformational adaptation presumably limits repulsive interactions. CPA C40 was utilized in the construction of the imidazole ring of axially chiral products 200 (Scheme 59) [89
Hot shape transformation: the role of PSar dehydration in stomatocyte morphogenesis
Beilstein J. Org. Chem. 2025, 21, 47–54, doi:10.3762/bjoc.21.5
- for the use in drug delivery systems [12]. In this regard, synthetic polypeptides emerge as a promising candidate for constructing biodegradable and biocompatible polymersomes. Leveraging the inherent presence of peptide-degrading mechanisms within the human body and the versatile chemical
Giese-type alkylation of dehydroalanine derivatives via silane-mediated alkyl bromide activation
Beilstein J. Org. Chem. 2024, 20, 3274–3280, doi:10.3762/bjoc.20.271
- functionalization (LSF) of peptide scaffolds. α,β-Unsaturated amino acids like dehydroalanine (Dha) derivatives have emerged as particularly useful structures, as the electron-deficient olefin moiety can engage in late-stage functionalization reactions, like a Giese-type reaction. Cheap and widely available
- , forming a new C(sp3)–C(sp3) bond. The reaction can be performed in a phosphate-buffered saline (PBS) solution and shows post-functionalization prospects through pathways involving classical peptide chemistry. Keywords: dehydroalanine; Giese-type reaction; hydroalkylation; photocatalysis; water
- ]. Amid the growing popularity of biomolecular drug candidates, the late-stage modification of peptide scaffolds has gained significant importance [28]. A particularly interesting class of amino acids for late-stage diversification consists of dehydroamino acids (Dha). Dha derivatives have shown
Synthesis of extended fluorinated tripeptides based on the tetrahydropyridazine scaffold
Beilstein J. Org. Chem. 2024, 20, 3174–3181, doi:10.3762/bjoc.20.262
- for peptide synthesis. Consequently, developing a simple and efficient methodology is still challenging. Our new strategy to synthesize these compounds is based on an aza-Barbier reaction on difluoro- or trifluoromethylated hydrazones. The thus obtained compounds will then be oxidized and cyclized in
- carbazate (NH2-NHCbz/NH2-NHBoc) were chosen as starting materials in order to obtain final building blocks suitable for peptide synthesis. While the synthesis of compound 3a was already reported [28], compounds 3b–f are not described in the literature. All the fluorinated hydrazones were obtained in good
- feature results will be further confirmed by the insertion of these cyclic β-dehydropiperazic acids in longer peptide sequences. Examples of bioactive tetrahydropyridazine derivatives. Linear and cyclic peptides incorporating the dehydropiperazic acid moiety. Piperazic acid and analogues and target
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
- silico to avoid rediscovery. They are the cornerstone of chemical structure metagenomics; a few examples in this area of research are described below. NRP biosynthesis and structure prediction NRPs are biosynthesized by either type I or II nonribosomal peptide synthetase (NRPS) [50][51]. Type I NRPS is a
- megaenzyme machinery that contains multiple modules arranged in an assembly line fashion, each of which is responsible for incorporating a single BB into the growing peptide intermediate (Figure 3a). One module typically contains one adenylation (A) domain that folds and operates semi-autonomously, which
- molecules Aside from an analysis of the BB usage pattern, real NRP-like molecules can be constructed in accordance to the predicted identity and order of the BBs. Brady and co-workers used solid-phase peptide synthesis to convert the predicted NRPs from virtual into reality; they called these molecules
gem-Difluorovinyl and trifluorovinyl Michael acceptors in the synthesis of α,β-unsaturated fluorinated and nonfluorinated amides
Beilstein J. Org. Chem. 2024, 20, 2946–2953, doi:10.3762/bjoc.20.247
- fluorinated Michael acceptors into peptide structures, which can act as the link between an active molecule and its cellular target [19][20]. Such endeavors hint at the potential of fluorinated acceptors in designing fluorinated peptidomimetics, an area attracting global research interest [21][22][23][24]. In
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
- protein conjugate was effectively done with various hydroxylamines with the assistance of the nucleophilic catalyst 5-methoxyanthranilic acid. The resultant histone protein conjugates were functionalized with TAMRA, biotin and the cell-penetrating peptide 'penetratin' through oxime ligation, achieving
Synthesis of fluoroalkenes and fluoroenynes via cross-coupling reactions using novel multihalogenated vinyl ethers
Beilstein J. Org. Chem. 2024, 20, 2691–2703, doi:10.3762/bjoc.20.226
- Fluoroalkenes are one of the important frameworks for a wide range of industrial fields. For example, they are used as a bioisostere of amide bonds in medicines and agrochemicals, and contribute to the synthesis of peptide medicines that are stable to enzymatic metabolism and possess high lipophilicity [1]. In
Applications of microscopy and small angle scattering techniques for the characterisation of supramolecular gels
Beilstein J. Org. Chem. 2024, 20, 2608–2634, doi:10.3762/bjoc.20.220
- more complex braided structures observable by SEM (Figure 9) [44]. An important feature of self-assembled networks is the defects that arise in the fibre structures as shown in the characterisation of β-hairpin peptide hydrogels by Yucel et al. [47]. The cryo-TEM characterisation indicated that the
- show that the self-assembly occurred on these length scales [85]. This data was used to show that hydrophobicity was a key factor in controlling the self-assembly of these compounds. The work by Greenfield et al. shows the advantageous tuneability of peptide amphiphiles and their ability to form gels
- fibre width and the changing mechanical properties observed in the materials. The networks are peptide-dominated at low agarose concentrations, and agarose-dominated at high agarose concentrations, resulting in distinct changes in structural morphology. Instead the variation in mechanical properties
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
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
- discuss the properties and applications of different chemical proteomics linkers with special focus on their fragmentation releasing diagnostic ions and how these may improve the confidence in identified active compound–peptide conjugates. The application of advanced search options improves the
- distinction of the probe–protein complex from the background. There are two levels on which the probe conjugates can be identified: either on the protein level as intact probe–protein conjugates or on the peptide level after protease digestion as a probe–peptide conjugate (Figure 1). Although the increased
- peptides or enhancement of the signal-to-noise ratio is necessary for successful analysis (Figure 1). The future challenge to complete the chemical proteomic analysis will include the absolute quantification of those identified NP–peptide conjugates to estimate protein occupancy (Figure 1). Although mass
Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis
Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196
- be developed by considering active structures. This was demonstrated by Crawford et al. [86] in their investigation of a peptide-catalysed atroposelective bromination (Figure 5). The authors found that the peptidic catalysts can broadly be defined in two categories of β-turns: a type I’ pre-helical
- based on a manual analysis of the probed substrates. The inclusion of electronic parameters led to a considerable improvement in predicting the enantioselectivity of a peptide-catalysed bisphenol desymmetrisation compared to their omission, showcasing the importance of capturing relevant molecular
- screening approaches [107][144][145][146][147]. Thereby, experimental efforts can be focused on the most promising candidates predicted by the model. Denmark and co-workers utilised such an approach to design highly selective catalysts for a peptide-catalysed annulation reaction [68]. Using conformer
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
- the production of non-ribosomal peptide synthetases with a molecular weight higher than 100 kDa [57]. However, these enzymes are often of great interest for specific applications in biomanufacturing. Cyclic GMP-AMP synthase (cGAS) is one of these enzymes. cGAS and its biocatalytic product 2’3’-cyclic
Computational toolbox for the analysis of protein–glycan interactions
Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180
- refinement. Among them, PROCHEK [98] is an open-source program that permits to check the quality of the protein structure by analysing the Ramachandran plots, the planarity of peptide bonds, the bad non-bonded interactions, the distortions of the geometry around the Cα atoms, the energies of hydrogen bonds
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
- spontaneously form in bovicin HJ50 to exert their natural activity and change spectra of antimicrobial effects when synthetically intramolecularly bound [17][18]. The biosynthesis of mature lanthipeptides involves the translation of lanA, which encodes a precursor peptide with two regions: a leader peptide that
- is recognized by post-translational enzymes and a core peptide where these enzymes produce the formation of Dha-Cys or Dhb-Cys residues. The post-translational modification enzymes involved span different functional domains (a cyclase and a dehydratase), and their activity is tightly controlled at
- catalyze the formation of Dha-Cys or Dhb-Cys [21]. Moreover, lanPt encodes a membrane protein with two ABC transporter domains and a C39 peptidase domain. The protein cleaves the leader peptide to generate mature lanthipeptides and exports them to the extracellular environment [22]. The diversity of
Ugi bisamides based on pyrrolyl-β-chlorovinylaldehyde and their unusual transformations
Beilstein J. Org. Chem. 2024, 20, 1773–1784, doi:10.3762/bjoc.20.156
- prepared and characterized. Surprisingly, a well-documented approach to obtain peptide-containing carboxylic acids through acid hydrolysis of the convertible isocyanide moiety in the Ugi bisamides proceeded in an unexpected manner in our case, leading to the formation of derivatives of amides of
- attempt to apply a well-documented approach for the subsequent synthesis of peptide-containing carboxylic acids by acid hydrolysis of the convertible isocyanide moiety in the Ugi bisamides proceeded in an unexpected manner: their treatment with acids led to elimination of the 2-chloroacetamide moiety and
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
- vitro enzymatic conversions (Scheme 9) [94]. The biosynthesis of 5 begins with the conversion of ʟ-tyrosine to tyrosine derivative 86 (Tyr*) by peroxygenase SfmD and the methyltransferases, SfmM2 and M3 [95][96]. Concurrently, two non-ribosomal peptide synthetase (NRPS) modules, SfmA and SfmB, catalyze
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