Effect of a photoswitchable rotaxane on membrane permeabilization across lipid compositions

• Udyogi N. K. Conthagamage,
• Lilia Lopez,
• Zuliah A. Abdulsalam and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2498–2512, doi:10.3762/bjoc.21.192

• proteins that are responsible for essential cellular functions [1]. As a result, the function and properties of lipid membranes are significantly influenced by their lipid composition, which varies across various domains of life, including mammalian, prokaryotic, and plant cells, and even between

Transformation of the cyclohexane ring to the cyclopentane fragment of biologically active compounds

• Natalya Akhmetdinova,
• Ilgiz Biktagirov and
• Liliya Kh. Faizullina

Beilstein J. Org. Chem. 2025, 21, 2416–2446, doi:10.3762/bjoc.21.185

• condensing abilities. Specific facial preferences are displayed as cholesterol interacts with different neighboring lipids and transmembrane proteins [33][34]. These biochemical interactions are poorly understood, so the synthesis of a «smoothed» cholesterol analogue provided an opportunity to experimentally

Synthetic study toward vibralactone

• Liang Shi,
• Jiayi Song,
• Yiqing Li,
• Jia-Chen Li,
• Shuqi Li,
• Li Ren,
• Zhi-Yun Liu and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2025, 21, 2376–2382, doi:10.3762/bjoc.21.182

• cyclization as the all-carbon quaternary center is formed in the last step. Given that the β-lactone moiety may act as a potential covalent inhibitor toward target proteins and that the sterically congested bicyclic skeleton presents a significant synthetic challenge, we herein report our synthetic study

Thiadiazino-indole, thiadiazino-carbazole and benzothiadiazino-carbazole dioxides: synthesis, physicochemical and early ADME characterization of representatives of new tri-, tetra- and pentacyclic ring systems and their intermediates

• Gyöngyvér Pusztai,
• László Poszávácz,
• Anna Vincze,
• András Marton,
• Ahmed Qasim Abdulhussein,
• Judit Halász,
• András Dancsó,
• Gyula Simig,
• György Tibor Balogh and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2220–2233, doi:10.3762/bjoc.21.169

• phosphate buffer for the “without cofactors” control. Aliquots (100 µL) were taken at zero time and at pre-defined time points of 30 and 60 minutes and quenched with an equal volume of cold acetonitrile. The samples were centrifuged at 2600 RCF for 10 minutes to pellet proteins. Supernatants were

Rhodium-catalysed connective synthesis of diverse reactive probes bearing S(VI) electrophilic warheads

• Scott Rice,
• Julian Chesti,
• William R. T. Mosedale,
• Megan H. Wright,
• Stephen P. Marsden,
• Terry K. Smith and
• Adam Nelson

Beilstein J. Org. Chem. 2025, 21, 1924–1931, doi:10.3762/bjoc.21.150

• , Biomedical Sciences Research Complex, University of St Andrews, St Andrews, KY16 9ST, UK 10.3762/bjoc.21.150 Abstract The value of small molecules that chemically modify proteins is increasingly being recognised and utilised in both chemical biology and drug discovery. The discovery of such chemical tools

• the discovery of small molecule modifiers for investigating and engineering proteins. Keywords: covalent probes; molecular diversity; rhodium carbenoids; Introduction Diverse sets of reactive probes can facilitate the discovery of chemical tools and drugs that chemically modify protein targets [1][2

• direct connective synthesis of diverse reactive probes. We envisage that such probes may enable chemical modification of non-cysteine residues within proteins, and may be valuable in investigating and engineering the biology of proteins. Envisaged connective synthesis of reactive probes 3 bearing S(VI

Synthesis, biological and electrochemical evaluation of glycidyl esters of phosphorus acids as potential anticancer drugs

• Almaz A. Zagidullin,
• Emil R. Bulatov,
• Mikhail N. Khrizanforov,
• Damir R. Davletshin,
• Elvina M. Gilyazova,
• Ivan A. Strelkov and
• Vasily A. Miluykov

Beilstein J. Org. Chem. 2025, 21, 1909–1916, doi:10.3762/bjoc.21.148

• . Electrochemical studies Alkylating agents are widely recognized for their ability to form covalent bonds with biological macromolecules (proteins, DNA). The literature discusses the interaction of small molecules with proteins, highlighting how linear sweep voltammetry (LSV) can be used to understand these

• disappearance of the albumin oxidation peak strongly suggests that all three investigated compounds can modify proteins under physiological conditions. Moreover, the fact that each agent was capable of this disruption aligns well with prior tests on the studied cell lines (PC-3, MCF-7, and HSF), where

• compounds 1–3 strongly indicates their ability to covalently modify nucleophilic sites in proteins. This finding underscores the potential of LSV as a rapid and effective tool for assessing alkylating reactivity, with implications for future drug development. Overall, this study offers meaningful insights

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

• -linking of polymers (such as PLGA and PEG), inorganic materials (such as gold and silica), or biomolecules (lipids and proteins), enabling efficient drug loading and controlled release [66][67][68]. Among them, amphiphilic CAs that incorporate both hydrophilic groups and hydrophobic alkyl chains through

Formal synthesis of a selective estrogen receptor modulator with tetrahydrofluorenone structure using [3 + 2 + 1] cycloaddition of yne-vinylcyclopropanes and CO

• Jing Zhang,
• Guanyu Zhang,
• Hongxi Bai and
• Zhi-Xiang Yu

Beilstein J. Org. Chem. 2025, 21, 1639–1644, doi:10.3762/bjoc.21.127

• widely distributed nuclear receptor proteins and include two subtypes, ERα [3][4] and ERβ [5][6]. These receptors can bind 17β-estradiol with similar affinity, facilitating the transfer of estrogen to various tissues in the body. Due to this, 17β-estradiol as non-selective ligand has been extensively

Heterologous biosynthesis of cotylenol and concise synthesis of fusicoccane diterpenoids

• Ye Yuan,
• Zhenhua Guan,
• Xue-Jie Zhang,
• Nanyu Yao,
• Wenling Yuan,
• Yonghui Zhang,
• Ying Ye and
• Zheng Xiang

Beilstein J. Org. Chem. 2025, 21, 1489–1495, doi:10.3762/bjoc.21.111

• -inflammatory, antimicrobial, antiparasitic, and plant growth regulating activities. For instance, cotylenin A (1) and fusicoccin A (2) function as molecular glues to stabilize the interactions between 14-3-3 proteins and their binding partners in plant and animal cells [8][9][10][11][12]. It has been reported

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

Studies on the syntheses of β-carboline alkaloids brevicarine and brevicolline

• Benedek Batizi,
• Patrik Pollák,
• András Dancsó,
• Péter Keglevich,
• Gyula Simig,
• Balázs Volk and
• Mátyás Milen

Beilstein J. Org. Chem. 2025, 21, 955–963, doi:10.3762/bjoc.21.79

• silico for non-peptide malignant brain tumor (MBT) antagonist activity, showing hits on three MBT-containing proteins [35]. Although Carex brevicollis DC has been observed to have a teratogenic effect on animals [1][36], which could be linked with the presence of the two mentioned β-carboline alkaloids

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

Synthesis of HBC fluorophores with an electrophilic handle for covalent attachment to Pepper RNA

• Raphael Bereiter and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 727–735, doi:10.3762/bjoc.21.56

• fluorescent protein (GFP), has revolutionized genetics by providing highly accurate real-time detection of fusion proteins in vitro and in vivo [1]. Pioneering work on GFP-tagged proteins for real-time monitoring of gene expression was first reported by Chalfie and co-workers in 1994 [2]. For a long time

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

• ubiquitous molecules in biology. Their functions permeate every aspect of life, including as essential components of oligonucleotide structure; as principal players in metabolism and energy storage; as motifs for the post-translational modification of proteins; and as partners in myriad supramolecular

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

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

• proteins. By harnessing light to drive chemical transformations, photoredox techniques can facilitate the synthesis of antibody bioconjugates. This perspective will discuss the drive to develop and empower photoredox methods applied to antibody functionalization. Keywords: antibodies; bioconjugation

• functionalized nature of polypeptides/proteins demands exquisite selectivity to target specific sites on the macromolecule of interest. In addition to the requisite features of the chemical methods outlined above, there are key requirements for synthetic methods used in ADCs, which include high site-selectivity

• covalent bioconjugation. Effective bioconjugation has been dramatically facilitated by the development of robust bioorthogonal reactions, which has revolutionized the field of chemical biology [17]. A bioorthogonal reactive group can be introduced into proteins via direct chemical coupling on specific

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

• receptors; molecular recognition; monosaccharides; tryptophan; Introduction Tryptophan plays a crucial role in a variety of biological processes [1][2]. For example, it is critical for electron transfer in proteins [3] and is a key component of several membrane proteins as well as short antimicrobial

• 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

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

• ] contributed by the amide links in proteins seems to be well-reproduced in our amide-linked cages. In summary, the ability to reliably and predictably access stable, soluble, low-symmetry cages, with tuneable functional group projections and tailorable flexibility, and all by dynamic covalent self-assembly

The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

• significantly spurred the scientific curiosity of researchers over the past few decades [1]. Intensive studies revealed that this subtle code of cell surface glycans is extensively responsible for monitoring a plethora of diverse biological phenomena like post-translational modification of proteins [2][3

• , usually proteins or lipids by the process of glycosylation producing glycoproteins or glycolipids, respectively. Nature executes these processes by enzymatic pathways [18] and is often flawless in its desired output. But the scarcity and the cumbersome purification of natural enzymes limit the use of

Synthesis, characterization, antimicrobial, cytotoxic and carbonic anhydrase inhibition activities of multifunctional pyrazolo-1,2-benzothiazine acetamides

• Ayesha Saeed,
• Shahana Ehsan,
• Muhammad Zia-ur-Rehman,
• Erin M. Marshall,
• Sandra Loesgen,
• Abdus Saleem,
• Simone Giovannuzzi and
• Claudiu T. Supuran

Beilstein J. Org. Chem. 2025, 21, 348–357, doi:10.3762/bjoc.21.25

• moiety was beneficial to optimize therapeutic activity of different analogs with lesser adverse effects [32]. Amide linkages are a common drug feature that comprises about 25% of the most prescribed and vended medication [33]. Mimicking biologically relevant structural features of proteins and enzymes

Antibiofilm and cytotoxic metabolites from the entomopathogenic fungus Samsoniella aurantia

• Rita Toshe,
• Syeda J. Khalid,
• Blondelle Matio Kemkuignou,
• Esteban Charria-Girón,
• Paul Eckhardt,
• Birthe Sandargo,
• Kunlapat Nuchthien,
• J. Jennifer Luangsa-ard,
• Till Opatz,
• Hedda Schrey,
• Sherif S. Ebada and
• Marc Stadler

Beilstein J. Org. Chem. 2025, 21, 327–339, doi:10.3762/bjoc.21.23

• Information File 1), it is likely that the activity of farinosones D (1) and A (2) does not interfere with the factors essential for fibronectin binding, particularly the fibronectin-binding proteins such as fibronectin binding protein (FnBPA and B) [18]. FnBPs are adhesions and are known to play a key role

Heteroannulations of cyanoacetamide-based MCR scaffolds utilizing formamide

• Marios Zingiridis,
• Danae Papachristodoulou,
• Despoina Menegaki,
• Konstantinos G. Froudas and
• Constantinos G. Neochoritis

Beilstein J. Org. Chem. 2025, 21, 217–225, doi:10.3762/bjoc.21.13

• be established as a C1 feedstock. [25]. Its high polarity and dielectric constant (it is miscible with water) [26], with the ability to solubilize a wide range of reagents, from salts to polymers, proteins and saccharides, renders formamide an excellent C1 building block [25][27]. Thus, our target

Chemical glycobiology

• Elisa Fadda,
• Rachel Hevey,
• Benjamin Schumann and
• Ulrika Westerlind

Beilstein J. Org. Chem. 2025, 21, 8–9, doi:10.3762/bjoc.21.2

• certainly by choice, but also by necessity. It is difficult to convey to non-glycoscientists how we still struggle with challenges that have been solved years or decades ago for proteins and nucleic acids. When molecular cloning and recombinant protein production became routine, these technologies were not

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

• ; 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