Molecular tweezer–peptide conjugates disrupt the protein–protein interaction between survivin and histone H3 essential in mitosis

• Catherine Gsell,
• Philipp Rebmann,
• Karina Opara,
• Christine Beuck,
• Peter Bayer,
• David Bier,
• Ingrid R. Vetter and
• Thomas Schrader

Beilstein J. Org. Chem. 2026, 22, 557–567, doi:10.3762/bjoc.22.41

• truncated human survivin with the peptide-tweezer molecules demonstrated that the peptide moiety binds the BIR domain as expected from the well-known published crystal structures of survivin with various peptides, but the tweezer itself, surprisingly, was bound to a putative Ca2+ ion and the side chain of

• (e.g., PDB ID 4A0J). The remainder of the peptides is usually disordered. Comparison of different peptides revealed that the N-terminal alanine is absolutely required for survivin binding, and no modification of the N-terminus is tolerated. Position 2 is probably uncritical, but most likely sensitive

• limiting the crystallization conditions [22]. Other co-crystallized peptides are AKERC from the N-terminus of shugoshin1 (6.2 µM, PDB ID 4A0I) [8] and a Smac-DIABLO 15-mer-peptide with only 121 µM affinity, that still crystallized at sufficiently high concentrations in complex with survivin (PDB ID 3UIH

Synthesis of a HDAC inhibitor–nanogold probe for cryo-EM visualization in class I HDAC co-repressor complexes

• Wiktoria A. Pytel,
• John W. R. Schwabe and
• James T. Hodgkinson

Beilstein J. Org. Chem. 2026, 22, 480–485, doi:10.3762/bjoc.22.35

• residues. Cysteines possess thiol side chains that exhibit strong affinity for gold, enabling them to form stable bonds with metal surfaces [21]. Such interactions may disrupt the native conformation of cysteine-containing proteins or peptides, potentially impairing the structural integrity of the CoREST

Recent advances in the stereoselective synthesis of distal biaxially chiral molecules

• Fanxing Zhou,
• Chen Zhang,
• Lingyu Sun,
• Yiyun Fang,
• Siming Zheng,
• Lina Hu,
• Mengyang Shen,
• Zhen Zhao,
• Wei Xu,
• Yunqiang Sun and
• Zi-Qiang Rong

Beilstein J. Org. Chem. 2026, 22, 461–479, doi:10.3762/bjoc.22.34

• and co-workers reported a class of Brønsted basic guanidinylated peptides that were able to catalyze atroposelective chlorination reactions, representing the first reported example of such a transformation (Scheme 20) [59]. This reaction employs a complementary strategy for the catalytic synthesis of

Efficient solid-phase synthesis and structural characterization of segetalins A–H, J and K

• Liangyu Liu,
• Wanqiu Lu,
• Quanping Guo and
• Zhaoqing Xu

Beilstein J. Org. Chem. 2025, 21, 2612–2617, doi:10.3762/bjoc.21.202

• sequences, coupling efficiency was significantly enhanced using a 1:1 mixture of 1-hydroxybenzotriazole (HOBt) and 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) in DMF [23]. Finally, we obtained crude linear peptides with 75% to 95% yields (Table 1). The critical head-to

• , successful macrocyclization was achieved by employing benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate (PyBOP) as the coupling reagent in DMF at a concentration of 10−3 M. After cleavage from the resin and global side-chain deprotection, the crude cyclic peptides were purified by preparative

• stability of intramolecular hydrogen bonds in the peptide backbone, thereby promoting the formation of stable secondary structures (such as α-helices or β-sheets) in cyclic peptides. Spectra acquired in H2O, 0.01×PBS, and 30% TFE (Table S1, Supporting Information File 1) demonstrate: (i) definitive β-sheet

Synthesis and characterization of a isothiouronium-calix[4]arene derivative: self-assembly and anticancer activity

• Giuseppe Granata,
• Loredana Ferreri,
• Claudia Giovanna Leotta,
• Giovanni Mario Pitari and
• Grazia Maria Letizia Consoli

Beilstein J. Org. Chem. 2025, 21, 2535–2541, doi:10.3762/bjoc.21.195

• [7], cyclic peptides [8], cucurbiturils [9], resorcinarenes [10], pillarenes [11], prismarenes [12], and calix[n]arenes have proven to be particularly valuable. Calix[n]arenes, a family of polyphenolic macrocyclic oligomers, are widely utilized in applications ranging from materials science to life

The high potential of methyl laurate as a recyclable competitor to conventional toxic solvents in [3 + 2] cycloaddition reactions

• Ayhan Yıldırım and
• Mustafa Göker

Beilstein J. Org. Chem. 2025, 21, 2389–2415, doi:10.3762/bjoc.21.184

• consisting of a combination of isoxazolidine rings [36][37][38][39][40][41]. It has been demonstrated that such cycloaddition reactions are also employed in the efficient preparation of biologically active molecules, including nucleosides, β-lactam class antibiotics, peptides, and amino acids, as well as

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

• the starting point 98-A. The unstable isomers were observed at low temperatures. Besides that, hemithioindigos have been used to operate as structural switches in peptides. Upon irradiation, the photoisomerisation of the hemithioindigo moiety is triggered, leading to an overall structural change of

Research progress on calixarene/pillararene-based controlled drug release systems

• Liu-Huan Yi,
• Jian Qin,
• Si-Ran Lu,
• Liu-Pan Yang,
• Li-Li Wang and
• Huan Yao

Beilstein J. Org. Chem. 2025, 21, 1757–1785, doi:10.3762/bjoc.21.139

• mechanisms that will be detailed in this article, researchers have made progress in the transport of amino acids and molecular peptides across membranes using macrocycles in recent years [35][36][37]. These works have paved the way for the potential application of remote-controlled membrane transport

Photoredox-catalyzed arylation of isonitriles by diaryliodonium salts towards benzamides

• Nadezhda M. Metalnikova,
• Nikita S. Antonkin,
• Tuan K. Nguyen,
• Natalia S. Soldatova,
• Alexander V. Nyuchev,
• Mikhail A. Kinzhalov and
• Pavel S. Postnikov

Beilstein J. Org. Chem. 2025, 21, 1480–1488, doi:10.3762/bjoc.21.110

• (in case of unsymmetrical iodonium salts) were studied. Keywords: arylation; benzamides; diaryliodonium salts; isonitriles; photoredox; Introduction Amides represent a crucial and ubiquitous structural motif in essential biomolecules including proteins and peptides [1], as well as in a wide array of

A versatile route towards 6-arylpipecolic acids

• Erich Gebel,
• Cornelia Göcke,
• Carolin Gruner and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 1104–1115, doi:10.3762/bjoc.21.88

• important role as building blocks for peptide synthesis [1][2][3][4][5], as organocatalysts [6][7][8][9][10] and as enzyme inhibitors [4][11][12][13]. The incorporation of such amino acids into peptides can, for example, influence peptide conformation, the binding affinity to receptors [14], as well as

• -inducing properties in peptides [22][23][24]. Furthermore, derivatives of pipecolic acid are known for their bioactivity as secondary metabolites [25][26][27] and for being building blocks for piperidine alkaloids [28] with a variety of uses. Results and Discussion Addressing specific positions in the ring

Dicarboxylate recognition based on ultracycle hosts through cooperative hydrogen bonding and anion–π interactions

• Wen-Hui Mi,
• Teng-Yu Huang,
• Xu-Dong Wang,
• Yu-Fei Ao,
• Qi-Qiang Wang and
• De-Xian Wang

Beilstein J. Org. Chem. 2025, 21, 884–889, doi:10.3762/bjoc.21.72

• metabolism [3][4]; cyclic peptides play critical roles in plant or bacterial defenses and as well as animal hormone signaling [5][6]; cyclic proteins exhibit diverse therapeutic functions [7]; and cyclic nucleotides are essential for molecular cloning and hold potential for disease treatment [8]. In contrast

Substituent effects in N-acetylated phenylazopyrazole photoswitches

• Radek Tovtik,
• Dennis Marzin,
• Pia Weigel,
• Stefano Crespi and
• Nadja A. Simeth

Beilstein J. Org. Chem. 2025, 21, 830–838, doi:10.3762/bjoc.21.66

• -art technologies ranging from energy-storage materials [6][7] to pharmacology [8][9][10][11], materials chemistry [12][13], control of peptides structure [14][15] or proteins [16], as antibacterial agents [17][18], smart coating [19], or multivalent photoresponsive systems [20][21], to name only a few

New advances in asymmetric organocatalysis II

• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 766–769, doi:10.3762/bjoc.21.60

• organocatalysis. Even toward the end of the 20th century, there have been a few pioneering studies that should be counted as examples of asymmetric organocatalysis. The works of Jacobsen, Miller, Shi, and Denmark et al. marked the early sparks of interest in this type of chemistry based on catalysis by peptides

Origami with small molecules: exploiting the C–F bond as a conformational tool

• Patrick Ryan,
• Ramsha Iftikhar and
• Luke Hunter

Beilstein J. Org. Chem. 2025, 21, 680–716, doi:10.3762/bjoc.21.54

• , fragrance chemicals, organocatalysts, and peptides. This comprehensive review summarises developments in this field during the period 2010–2024. Keywords: conformational analysis; medicinal chemistry; organofluorine chemistry; stereoselective fluorination; Introduction In the art of origami, a

• scaffolds – alkanes – then we will progress to ethers, alcohols, sugars, amines (and their derivatives), carbonyl compounds, peptides, and finally sulfur-containing compounds. By arranging the material in this way, we hope that newcomers to the field might be able to readily envisage ways to apply these

• of this phenomenon will be presented in section 7 (peptides). It was stated above that the NH···F interaction (i.e., II, Figure 12) is not dominant. However, this interaction has been successfully exploited within the slightly different structural context of anilides (e.g., 113–115, Figure

Asymmetric synthesis of fluorinated derivatives of aromatic and γ-branched amino acids via a chiral Ni(II) complex

• Maurizio Iannuzzi,
• Thomas Hohmann,
• Michael Dyrks,
• Kilian Haoues,
• Katarzyna Salamon-Krokosz and
• Beate Koksch

Beilstein J. Org. Chem. 2025, 21, 659–669, doi:10.3762/bjoc.21.52

• 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

• aromatic–aromatic interactions. For example, our group highlighted the influence of different fluorinated phenylalanine analogs on the aggregation rate of amyloid-forming NFGAIL peptides [14]. Amino acids 2 and 3, with their respective fluorination pattern, might be fascinating compounds in this context

Photocatalyzed elaboration of antibody-based bioconjugates

• Marine Le Stum,
• Eugénie Romero and
• Gary A. Molander

Beilstein J. Org. Chem. 2025, 21, 616–629, doi:10.3762/bjoc.21.49

• conjugation methods often face challenges related to site-selectivity and heterogeneous product mixtures, highlighting the need to develop new, innovative chemical strategies. Photoredox chemistry emerges as a powerful tool in this context, enabling precise, mild, and selective modifications of peptides and

• disulfide bridging sites in biomolecules to introduce specific functional groups (Figure 6) [44]. The bioconjugation reaction is based on thiol–yne coupling. Originally developed on peptides and proteins, this approach was applied to a fragment antigen-binding (Fab) antibody fragment (approximately 46 kDa

Binding of tryptophan and tryptophan-containing peptides in water by a glucose naphtho crown ether

• Gianpaolo Gallo and
• Bartosz Lewandowski

Beilstein J. Org. Chem. 2025, 21, 541–546, doi:10.3762/bjoc.21.42

• Gianpaolo Gallo Bartosz Lewandowski Laboratory of Organic Chemistry, ETH Zürich, Vladimir-Prelog-Weg 3, 8093 Zürich, Switzerland 10.3762/bjoc.21.42 Abstract Tryptophan fulfills a plethora of important functions in nature both in its free form and as a component of peptides and proteins. Selective

• peptides [4][5]. Tryptophan also serves as a substrate to produce hormones such as serotonin or melatonin [6][7]. Due to the biological relevance of tryptophan synthetic receptors for this amino acid are highly sought after [8]. From a biological perspective it is especially desirable to achieve selective

• aqueous media is limited (Figure 1a–c) [13][14][15][16][17][18]. In particular, receptors which bind tryptophan residues in peptides are rare [19][20]. Recently, we developed a glucose-based naphtho crown ether 1 (Figure 1d) which binds amino acid methyl esters with aromatic side chains chemoselectively

Beyond symmetric self-assembly and effective molarity: unlocking functional enzyme mimics with robust organic cages

• Keith G. Andrews

Beilstein J. Org. Chem. 2025, 21, 421–443, doi:10.3762/bjoc.21.30

• release [216] and even switch catalysis on and off [196]. MOCs containing peptides in the edge pieces also look promising to direct catalysis [217]. Extended frameworks Metal-organic frameworks (MOFs) [218][219] and covalent organic frameworks (COFs) [220][221][222][223][224] are well-studied as

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations

• Seungmin Lee,
• Minsuk Kim,
• Hyewon Han and
• Jongwoo Son

Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12

• yields (16a–c). Moreover, alkyl groups were tolerated during the formation of N-acyl iminophosphoranes (16d, 16f). It is noteworthy that dioxazolones derived from bioactive motifs, such as peptides, natural products, and commercially available drugs were also compatible with this transformation

• late-stage functionalizations of complex scaffolds such as peptides, drug molecules, and natural products containing unprotected free OH and NH groups are anticipated. Proposed reaction pathway for the copper-catalyzed synthesis of δ-lactams from dioxazolones. Proposed reaction mechanism for the copper

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

Hot shape transformation: the role of PSar dehydration in stomatocyte morphogenesis

• Remi Peters,
• Levy A. Charleston,
• Karinan van Eck,
• Teun van Berlo and
• Daniela A. Wilson

Beilstein J. Org. Chem. 2025, 21, 47–54, doi:10.3762/bjoc.21.5

• ) emerged as another solvent yielding monodisperse assemblies. HFIP promotes formation of alpha helices in peptides and this property yielded vesicles with different morphologies [30]. The resulting vesicles looked darker compared to those formed in DMF, as observed through TEM (Supporting Information File

Synthesis of extended fluorinated tripeptides based on the tetrahydropyridazine scaffold

• Thierry Milcent,
• Pascal Retailleau,
• Benoit Crousse and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2024, 20, 3174–3181, doi:10.3762/bjoc.20.262

• intramolecular Michael addition. Preliminary conformational studies on tripeptides including this scaffold in the central position show an extended conformation in solution (NMR) and in the solid state (X-ray). Keywords: fluoroalkyl groups; heterocycles; hydrazino acids; peptides; tetrahydropyridazines

• ; Introduction The synthesis of molecules capable of mimicking the various secondary structures and key functions of proteins is a major challenge in medicinal chemistry, especially in the fields of protein–protein interactions [1][2]. Accordingly, the incorporation of heterocyclic amino acids into peptides

• tetrahydropyridazine scaffold is also found in numerous natural linear or cyclic peptides such as svetamycins or antrimycins as dehydropiperazic acid (Figure 2) [10]. Whereas many publications have been devoted to the synthesis and structure of piperazic acid derivatives (dehydro, chloro, hydroxy, …) [11][12], nothing

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• approaches Alzheimer’s disease (AD) The pathogenesis of AD is still not clear but is marked as a multifactorial disease [24], including a good deal of hypotheses involving the cholinergic hypothesis, glutamate excitotoxicity, tau aggregation, abnormal extracellular accumulation of Aβ peptides, and oxidative

• carboxylic building block. The obtained molecules were evaluated for their ability to inhibit β-amyloid aggregation by the interaction with two β‐amyloid peptides, Aβ1‐42 and AβpE3‐42. The aggregation inhibition experiment, which measures the decrease of fluorescence, was carried out with the thioflavin T

• –melatonin hybrids (LATMHs), deciding to incorporate melatonin as a new target for the MTDL [39]. Melatonin has the ability to combat OS, which is a crucial factor in the pathogenesis of AD. Moreover, it plays a neuroprotective role against Aβ-peptides and easily crosses the blood–brain barrier (BBB

Chemical structure metagenomics of microbial natural products: surveying nonribosomal peptides and beyond

• Thomas Ma and
• John Chu

Beilstein J. Org. Chem. 2024, 20, 3050–3060, doi:10.3762/bjoc.20.253

• . While microbial nonribosomal peptides have been the focus of chemical structure metagenomics efforts thus far, it is in principle applicable to other natural product families. The future outlook of this new approach will also be discussed. Keywords: bioinformatics; chemical structure metagenomics

• ; natural products; natural product discovery; nonribosomal peptides; Introduction Natural products present diverse structures to elicit a wide range of biological activities and are of paramount importance to both translational science and basic research. Despite not knowing the underlying active

• approaches have already facilitated the discovery of numerous new bioactive molecules [29][30][31][32][33][34][35][36] and shed light on the scope of past discovery efforts by uncovering select oversampled/underexplored niches in the natural product chemical spaces [37]. While nonribosomal peptides (NRP