Amino acid-based surfactants: sustainable synthesis and antimicrobial mechanisms

• Rafaela Gomes Bezerra,
• Lourdes Pérez and
• Francisco Fábio Oliveira de Sousa

Beilstein J. Org. Chem. 2026, 22, 1067–1085, doi:10.3762/bjoc.22.85

• crystallization to improve economic and environmental viability. The diversity of these molecular architectures enables systematic evaluation of the effects of charge density, alkyl chain length and position, and aromatic moieties on antimicrobial performance, as extensively documented by Pérez and co-workers [4

• ) [82]. Biofilm penetration and synergistic effects Amino acid-based surfactants exhibit unique capabilities in penetrating biofilm matrices, thereby enhancing the susceptibility of pathogens to co-administered antimicrobial agents. For example, arginine-tryptophan surfactants (LTAM) demonstrate potent

Synthesis of functionalized, 13-alkyl-substituted coralyne derivatives and investigation of their interactions with duplex and abasic site-containing DNA

• Laurin Beckmann,
• Jason Lennard Kunze,
• Hannah Karola Strunk,
• Maurice Michel and
• Heiko Ihmels

Beilstein J. Org. Chem. 2026, 22, 1057–1066, doi:10.3762/bjoc.22.84

• averaging” with factor of 10 (absorption, CD and LD) or 20 (emission). Materials Alfa Aesar GmbH + Co. KG (Kandel, DE): NaI (99%); BLD Pharmatech Ltd. (Shanghai, CHN): benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (PyBOP, 98%); Carl Roth GmbH + Co. KG (Karlsruhe, DE): N,N

• (2.50 M in hexane); Tokio Chemical Industries Co., Ltd. (Tokio, JPN): papaverine hydrochloride (98%). Column chromatography: silica gel (60 M, 40–63 µm, 230–400 mesh ASTM, Macherey-Nagel GmBH & Co. KG). Ethyl 4-iodobutanoate [46] and 1,1-dimethylethyl N-(3-aminopropoxy)carbamate hydrochloride [37] were

Synthesis of novel 1,2,4-oxadiazole-isoxazoline hybrids and their in silico potential with adenosine receptors

• Pshtiwan S. Mohammed,
• Mohammed K. S. Dalo,
• Onur C. Yazıcı,
• Muhammet Yildirim and
• Akın Sağırlı

Beilstein J. Org. Chem. 2026, 22, 1033–1047, doi:10.3762/bjoc.22.82

• strong binding affinities toward the adenosine A₁ receptor (−10.0 to −8.3 kcal/mol), surpassing the co-crystallized ligand and engaging in key stabilizing interactions within the binding pocket. Furthermore, ADMET predictions indicated favorable drug-likeness, high gastrointestinal absorption, and

• the observed product. In silico studies Molecular docking studies with adenosine receptor A molecular docking study was performed to obtain a comprehensive insight into the binding modes of the 1,2,4-oxadiazole-isoxazoline hybrids (7a–ay) and the co-crystallized reference ligand (1-butyl-3-(3

• chronic and neuropathic pain, whereas its inhibition (A1 antagonism) leads to increased alertness and modulation of renal blood flow [63][65]. The predicted binding affinities of the 7a–ay derivatives, evaluated in both possible enantiomeric forms (R and S), together with those of the co-crystallized

Synthesis and optical resolution of 4,5-diaminohomoadamantane: a promising scaffold for chiral ligands and bioactive compounds

• Polina A. Man’kova,
• Vadim A. Shiryaev,
• Olga S. Podlipnova,
• Marat M. Khisyamov,
• Dmitry S. Nikerov,
• Alexander N. Reznikov and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2026, 22, 1013–1022, doi:10.3762/bjoc.22.80

• cell damage [57], and activity against Staphylococcus aureus was noted for peroxysampsone A С [58]. Basarić and co-workers showed that the replacement of 2-substituted adamantane by a homoadamantane skeleton led to enhanced antiproliferative activity (compound D) [59]. Compound E showed efficacy

Z-Selective semihydrogenation of alkynes via Ni/Lewis acid synergistic catalyzed system using DMF as hydrogen source and solvent

• Lei Kang,
• Haifeng Gao and
• Luo Yang

Beilstein J. Org. Chem. 2026, 22, 1004–1012, doi:10.3762/bjoc.22.79

• . outlined the state-of-the-art progress on stereoselective semihydrogenation of alkynes catalyzed by first-row (3d) transition metals, which attract substantial attention owing to their natural abundance and low toxicity [5]. In recent years, homogeneous catalysts based on Ni, Cu, Rh, and Co have shown

• diphenylacetylene (1a), motivated by the practical limitations associated with previous precious-metal Pd catalysts. Capitalizing on DMF's capacity to act as both solvent and hydrogen source, we investigated a Ni/Lewis acid co-catalytic approach. Employing Co(OAc)2·4H2O as the Lewis acid co-catalyst, we first

• evaluated the influence of the nickel precursor. As summarized in Table 1, the reaction of 1a was performed in DMF (0.8 mL) at 150 °C for 24 h, using various Ni sources (20 mol %) and Co(OAc)2·4H2O (50 mol %). When NiCl₂ was used, 2a (cis-stilbene) was obtained in 68% GC yield (Table 1, entry 1). In

The role of spacer length and flexibility in peptide self-assembly

• Julian Link,
• Albin Lahu,
• Manfred Wagner,
• Tanja Weil and
• David Y. W. Ng

Beilstein J. Org. Chem. 2026, 22, 986–996, doi:10.3762/bjoc.22.77

• behavior of molecules by monitoring spectral changes upon increasing the fraction of an organic co-solvent. A gradual, linear change in signal intensity or chemical shift with increasing co-solvent content is indicative of simple dissolution and bulk solvent effects. In contrast, a pronounced transition

• this co-solvent composition due to the formation of substantially larger aggregates that undergo rapid transverse relaxation. The pronounced aggregation of these conjugates is further evidenced by inspection of the corresponding NMR tubes, where clear solid–liquid phase separation was observed

• % results in the emergence of sharp, well-resolved signals for both peptides 6 and 7. This pronounced transition suggests that the aggregates present in aqueous media are disrupted once a critical level of organic co-solvent is reached. The additional increase in TFE-d3 content to 50% does not produce

Novel macrocycles: from synthesis to supramolecular function

• Veronica Iuliano,
• Carmen Talotta,
• Margherita De Rosa,
• Paolo Della Sala,
• Konrad Tiefenbacher,
• Pablo Ballester and
• Carmine Gaeta

Beilstein J. Org. Chem. 2026, 22, 982–985, doi:10.3762/bjoc.22.76

• ], cryptands [3], and spherands [4], calixarenes and resorcinarenes feature aromatic cavities that accommodate a wide variety of neutral and charged organic guests. A major advance in the field occurred in 2008, with the introduction of pillararenes by Ogoshi and co-workers [9]. Composed of 1,4-dialkoxybenzene

• macrocycles: from synthesis to supramolecular function”. The aim of this collection is to highlight recent advances in the design, synthesis, and functional applications of macrocyclic supramolecular receptors. The issue opens with the work of Isaacs and co-workers [33], who report the synthesis of a new

• functional soft materials. Asymmetric frameworks are also central to the research reported by Niemeyer and co-workers [36], who focused on the synthesis of crown ethers bearing one or two BINOL units. Their paper outlines highly practical synthetic routes to open a diverse library of chiral architectures

Electrochemical reduction of unsaturated carbon–carbon bonds via 3d transition-metal catalysis

• Geon Kang,
• Minki Jeon,
• Pooja Kumari Jat,
• Cheoljae Kim and
• Isaac Choi

Beilstein J. Org. Chem. 2026, 22, 955–981, doi:10.3762/bjoc.22.75

• through inner-sphere substrate organization. From this perspective, alkene reduction is relatively more challenging because of the lower π-basicity of alkenes. Alternatively, outer-sphere electron transfer, mediated by electrolysis, or the strategic use of redox mediators and co-catalysts could also

• indicated that protonation of low-valent cobalt species leads to the formation of a Co(III)–H intermediate [95], which then reacts with the alkyne to regenerate the monoligated Co(II) catalyst (Scheme 3D). DFT calculations further support that proton delivery from HFIP to the cobalt–alkyne adduct proceeds

• along an energetically viable pathway with a notably low barrier, consistent with a concerted mechanism. These findings collectively delineate the proposed Z-selective reduction catalytic cycle. Moreover, bond dissociation energy analysis revealed that the relatively weak Co–H (42.4 kcal mol−1) and Co–C

A practical CO₂-mediated synthesis of 5,6-carboxylated silicon-rhodamines for targeted probe development

• Dongjie Hou,
• Shaowei Wu,
• Ning Xu,
• Pengjun Bao,
• Wenhao Jia,
• Qinglong Qiao and
• Zhaochao Xu

Beilstein J. Org. Chem. 2026, 22, 915–924, doi:10.3762/bjoc.22.72

• readily available CO2, this method delivers carboxylated SiR derivatives in 60–93% yields while avoiding the use of t-BuLi, toxic CO, and expensive palladium catalysts. In addition, the crude carboxylation mixtures can be directly subjected to amide coupling without chromatographic purification, enabling

• cell permeability [25][26]. Johnsson and co-workers further showed that SiRs can exist in a nonfluorescent spirolactone form, whereas target binding shifts the equilibrium toward the fluorescent zwitterionic form, thereby generating a strong fluorogenic response (Figure 1a) [27][28][29]. This behavior

• -catalyzed carbonylation using in situ-generated CO then furnished the corresponding carboxylated SiRs in 50–90% yields. Although this approach significantly improved synthetic efficiency, it still relies on specialized setups for CO generation and expensive palladium catalysts, thereby increasing

Palladium-catalyzed benzocyclization reactions of quinoline-2-carboxamides via sequential C–H/N–H functionalization

• Shoichi Sugita,
• Kentaro Okano and
• Atsunori Mori

Beilstein J. Org. Chem. 2026, 22, 905–914, doi:10.3762/bjoc.22.71

• carbon–metal species (Scheme 1a). Fagnou and co-workers reported direct arylation reactions with palladium(II) acetate to synthesize biaryl compounds via concerted metalation–deprotonation (CMD; Scheme 1b) [25][26][27]. Buchwald, Hartwig, and co-workers explored carbon–nitrogen coupling reactions that

The trans-influence in gold chemistry from a catalytic perspective

• Manfred Bochmann

Beilstein J. Org. Chem. 2026, 22, 838–856, doi:10.3762/bjoc.22.66

• . This effect is probably more dominant in gold chemistry than in most other transition-metal complexes; it can on occasions appear even more important than the formal oxidation state and d-electron count. Tilset and co-workers have recently summarised the importance of the trans-influence in C^N

• structure and bonding in the transition state. As summarised in an early review by Appleton, Clark and Manzer [22], both σ-donation and π-effects of the ligands are important. Ligands with strong trans-influence are typically either strong π-acceptors such as CO and CN−, and strong σ-donors, like

• trialkylphosphines, anionic carbon and hydride ligands. N- and O-lone pair donors (pyridine, water) are weak ligands. The following indicative series is typical for Pt(II), although there may be slight variations in the specific ordering depending on the complex type under investigation: CO, CN−, C2H4 > P(alkyl)3

Knoevenagel condensation of 4,5- and 1,8-diazafluorenes

• Darya S. Cheshkina,
• Christina S. Becker,
• Alina A. Sonina and
• Maxim S. Kazantsev

Beilstein J. Org. Chem. 2026, 22, 803–812, doi:10.3762/bjoc.22.62

• diazafluorene fragments along (a + b) (Figure 2b). The stacks of molecules are linked together via π···π and C–H···π interactions between pyridine fragments (Figure 2c). To further evaluate the complexation behavior of 4,5-DPDAF we co-crystallized the compound with ZnCl2 resulting in a unique complex (Zn–4,5

Synthetic study of vic-bromination of diarylacetylenes, easy purification and separation

• Akane Togo,
• Hiyono Suzuki,
• Yuto Akai,
• Makoto Matsumoto,
• Yoshinori Suzuma,
• Hidehiko Kodama and
• Kouichi Matsumoto

Beilstein J. Org. Chem. 2026, 22, 795–802, doi:10.3762/bjoc.22.61

• Akane Togo Hiyono Suzuki Yuto Akai Makoto Matsumoto Yoshinori Suzuma Hidehiko Kodama Kouichi Matsumoto Department of Chemistry, School of Science and Engineering, Kindai University, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan Nippon Pharmaceutical Chemicals Co., Ltd., 2-8-18 Chodo, Higashi

• reported studies suggest that it is surprisingly difficult to obtain the E isomer selectively (Scheme 1). For selected examples, Espenson and co-workers reported in 1999 that E-selective bromination of diphenylacetylene took place by using H2O2, NaBr, and AcOH in the presence of MTO (methyltrioxorhenium

• was reported for the Z isomer (Scheme 1b). As another example in 2008, Adimurthy and co-workers proposed the combination of NaBr-NaBrO3 in AcOH in order to prepare in-situ generated Br2, which was reacted with diphenylacetylene to give no selectivity between E and Z isomers of 1,2-dibromo-1,2

Design, synthesis, and biological evaluation of FXR/ASK1 dual-target modulators

• Xi Zhang,
• Jingyan Wang,
• Ziqiang Zhao,
• Caiyi Wang,
• Zenghui Ye,
• Wei-Yuan Ma,
• Jian-Xing Xu and
• Fengzhi Zhang

Beilstein J. Org. Chem. 2026, 22, 771–781, doi:10.3762/bjoc.22.59

• -aliphatically substituted 4H-1,2,4-triazolopyridine biaryl scaffold of selonsertib [31][39][40], as key pharmacophores. In the co-crystal structure of hFXR-LBD with GW4064 [41], the isoxazole core coordinates the π-cation interaction between His 447 and Trp 469; the 5-isopropyl group is embedded into a

• systems or the phenyl ring at the 3-position of the isoxazole to enhance hydrophilicity and improve pharmacokinetic properties [42]. Co-crystallization of GS-4997 with ASK1 unveiled key stabilizing interactions in the active site. Specifically, the amide carbonyl forms a hydrogen bond with the backbone

Preparation of 3-(alkylamino)imidazo[1,2-a]pyridine-2-carbaldehydes via Kornblum oxidation and unexpected ring-opening reactions of the corresponding alcohols under oxidative conditions

• Sandile J. Mkhize,
• Memory Zimuwandeyi,
• Manuel A. Fernandes,
• Amanda L. Rousseau and
• Moira L. Bode

Beilstein J. Org. Chem. 2026, 22, 763–770, doi:10.3762/bjoc.22.58

• mechanism. Oxidative ring-opening of imidazo[1,2-a]pyridines has been reported previously, but in these cases different ring-opened products were identified. These previous results are compared to our present report in Figure 5. Wang and co-workers [30] reported ring-opening accompanied by loss of a carbon

• atom, giving rise to benzamides, while Wu and co-workers [31] reported ring-opening to give either benzamides or α-ketoamides. This is in contrast to our own report, where only the oxalamide derivatives 18 were isolated. Two other oxidation methods, IBX and enzymatic oxidation using T. versicolor

Synthesis and biological evaluation of new brassinosteroid analogs with C-22 benzoate function

• María Núñez,
• Camila Escobar,
• Mario Párraga,
• Mauricio Soto,
• Luis Espinoza-Catalán,
• Katy Díaz and
• Andrés F. Olea

Beilstein J. Org. Chem. 2026, 22, 753–762, doi:10.3762/bjoc.22.57

• structurally and functionally comprehensive model system resolved by X-ray crystallography. Unlike BRL1 and BRL3, for which only monomeric ectodomain structures are available, the 4M7E structure enables modeling of the full receptor–co-receptor assembly required for the “molecular glue” mechanism involving

Rongalite addition to dienones: diastereoselectivity in cyclic sulfone synthesis; stereochemical rationalization and prospects as a general conjugate nucleophile

• Melina Goga,
• Hao Zong,
• James Franco,
• Jazmine Prana,
• Rudolph Michel,
• Antonia Muro,
• Elana Rubin,
• Janet Brenya,
• Henk Eshuis and
• Magnus W. P. Bebbington

Beilstein J. Org. Chem. 2026, 22, 742–752, doi:10.3762/bjoc.22.56

• comparison with other readily available sulfinates. Results and Discussion Confirmation of diastereoselectivity In our initial report, we supposed that the major product was the trans-isomer, following the analysis of Detty and co-workers [22], who prepared sulfones 1a and 1b (Figure 2) by a conventional

Synthesis of heterocycles based on azomethine ylides from α-amino acids (or amines) and carbonyl compounds

• Ekaterina V. Berezhnaya,
• Alexander I. Ponyaev,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2026, 22, 705–741, doi:10.3762/bjoc.22.55

• development of this method is also presented. Review Imine derivatives as precursors of azomethine ylides Azomethine ylides based on iminoesters In 2002, Zhang and co-workers described a highly enantioselective Ag(I)-catalyzed (3 + 2) cycloaddition of azomethine ylides from α-(arylimino)esters using AgOAc as

• sulfone, cinnamic, croton, and methacrylic aldehydes, and β-nitrostyrene as dipolarophiles. Depending on the dipolarophile used, pyrrolizidines 11 were obtained with an enantiomeric excess of up to 94% and yields of up to 92%. In 2009, Wang and co-workers reported the catalytic endo-selective

• cyclopropenes, resulting in a variety of complex 3-azabicyclo[3.1.0]hexane derivatives as a single isomer in excellent yields (up to 99%) and enantioselectivities (97–99% ee) [46]. In [47], Singh and co-workers reported an enantioselective (3 + 2) cycloaddition reaction of iminoesters 12 with substituted

Synthesis of depressin, cryptomeridiol and 4-epi-cryptomeridiol enabled by a terpenoid chiral pool-producing platform

• Yao Kong,
• Tao Wang,
• Chen Wang,
• Pengcheng Zhang,
• Yuanning Liu,
• Kaibiao Wang,
• Fen Liu,
• Hongli Jia and
• Zhengren Xu

Beilstein J. Org. Chem. 2026, 22, 683–690, doi:10.3762/bjoc.22.53

• Tanacetum parthenium) [52] encoding genes were synthesized and cloned into the pET28a-based plasmid, to give pET28a-cs and pET28a-gas, respectively. The E. coli heterologous host was then co-transformed with pXT02007/pET28a-gas and pXT02013/pET28a-cs, to afford strains XT02019 (for production of germacrene

Harnessing light energy with molecules

• Grace G. D. Han,
• Mogens Brøndsted Nielsen and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2026, 22, 680–682, doi:10.3762/bjoc.22.52

• approaches of optimization with regard to their light harnessing efficiency, energy storage capacity, and storage time. Structural modifications and studies of the norbornadiene/quadricyclane (NBD/QC) photo-/thermoswitch couple are covered in several articles. In a publication by Kerzig, Ihmels, and co

• -workers [4], the π-system of monoaryl-substituted NBDs was synthetically extended by acetylenic bridges. In addition, Hebborn, Ihmels, and co-workers [5] show that 19F NMR spectroscopy enables unambiguous identification of mono- and bisQC intermediates in the sequential photoreactions of a fluorinated

• structure by a heteroatom (oxygen or nitrogen) in donor–acceptor, push–pull NBD derivatives are reported. In a computational study, Pawar and co-workers [7] further expanded the NBD structure by elongating the unsaturated bridge with different heteroatoms or functional groups. Azobenzenes, interconverting

Using generative AI to transform peptide hits into small molecule leads

• Joshua Mills and
• Yu Heng Lau

Beilstein J. Org. Chem. 2026, 22, 672–679, doi:10.3762/bjoc.22.51

• functionality to recapitulate the pharmacophore of the original peptide (Class D according to the classification proposed by Grossmann and co-workers [10]). The challenge of transforming a peptide binder into a small molecule mimic is not new [11]. Indeed, there are well-known historical examples of blockbuster

• experimental co-crystal structure of the bound complex, standard medicinal chemistry principles are used to probe structure–activity relationships (SAR) and determine the key interactions that form a minimal pharmacophore, supported by classical physics-based molecular modelling methods such as molecular

• dynamics (MD) and docking (Figure 1). As an illustrative example, Yoshida and co-workers at Shionogi reported the design of small molecule inhibitors of nicotinamide N-methyltransferase [14] and β-herpesvirus proteases [15], starting from cyclic peptide hits obtained by mRNA display with flexible in vitro

Photoorganocatalytic trifluoromethylation of (het)arenes in green conditions

• Egor N. Boronin,
• Svetlana E. Kaurkina,
• Milena M. Svetlakova,
• Anton S. Bolshakov,
• Maxim V. Arsenyev,
• Vasilii F. Otvagin,
• Alexey Yu. Fedorov,
• Timothy Noël and
• Alexander V. Nyuchev

Beilstein J. Org. Chem. 2026, 22, 662–671, doi:10.3762/bjoc.22.50

• approaches can be regarded as among the most environmentally sustainable methods for trifluoromethylation. MacMillan and co-workers reported the photochemical trifluoromethylation of arenes and heteroarenes using Ru- and Ir-based photocatalysts together with trifluoromethanesulfonyl chloride (TfCl) in the

• transformations were performed in acetonitrile, which reduces their ecological compatibility, particularly for large-scale applications. Tlili and co-workers have described the use of an organic photocatalyst for the CF3-functionalization of styrenes with the Langlois reagent (sodium trifluoromethanesulfinate

Advantages of PROTACs in achieving selective degradation of homologous protein families

• Luxi Yang,
• Xinfei Mao,
• Jingyi Zhang,
• Jing Shu,
• Wenhai Huang,
• Xiaowu Dong,
• Yinqiao Chen and
• Mingfei Wu

Beilstein J. Org. Chem. 2026, 22, 628–661, doi:10.3762/bjoc.22.49

• pharmaceutical chemists. In 2019, Gray, Zhang and co-workers designed a PROTAC-1 (1) to degrade CDK4/6 [21]. To construct compound 1 they used the CDK4/6 inhibitor palbociclib as the POI ligand, pomalidomide, which combines with CRBN as the E3 ligand and a 4-carbon alkyl linker to connect them. The compound can

• ability to target the degradation of CDK6, and proteomics results also show that compound 2 has no degradation effect on CDK4. In 2020, Benowitz and co-workers carried out a project to explore the impact of different E3 ligands on the selective degradation of CDK4/6 [57]. In their research, they designed

• ligand and E3 ligand. Similarly, the research results show that compound 3 can also selectively degrade CDK6. Meanwhile, Rana, Natarajan and co-workers developed a PROTAC-6 (4) based on palbociclib and pomalidomide [58] (Figure 2). In the study, the researchers evaluated the degradation effect of

Hydrogen production from formic acid catalyzed by NHC–Cu complexes

• Orlando Santoro and
• Catherine S. J. Cazin

Beilstein J. Org. Chem. 2026, 22, 620–627, doi:10.3762/bjoc.22.48

• have also been explored. Beller and co-workers reported the first Fe catalyst bearing a phosphine ligand able to produce H2 with a TON of 1942 in the absence of additives [32]. A well-defined pincer–Fe complex allowing FA decomposition was reported by Milstein and co-workers [33]. While high TONs (up

• such as Co [35][36], Ni [37][38], Al [39][40], and Mn [41][42][43] have been released. In this scenario, copper systems remain widely unexplored and, generally, have displayed low activity, regardless of the oxidation state of the Cu precursor and of the presence/absence of additives [44][45][46][47

• ]. Finally, a Cu(I)–formato complex able to promote FA dehydrogenation in the absence of any additive was very recently reported by Berthet, Cantat and co-workers [48]. During the past decades, NHC–Cu complexes have shown to be efficient catalysts in a plethora of reactions. Indeed, they guarantee better

Towards the targeted protein degradation of CK2: design and synthesis of CAM4066-based PROTACs

• Sophie Day-Riley,
• Sona Krajcovicova,
• Aryaman Raj Sokhal,
• Jan L. Venne,
• Paul Brear,
• Marko Hyvönen,
• Benjamin C. Whitehurst,
• Jason S. Carroll and
• David R. Spring

Beilstein J. Org. Chem. 2026, 22, 611–619, doi:10.3762/bjoc.22.47

• broader kinome perturbation. The first design objective was therefore to identify a suitable exit vector for linker attachment that would allow productive E3-ligase recruitment without compromising the established binding geometry of CAM4066. Inspection of the co-crystal structure of 1 bound to CK2α

• yield acid S13. Isothermal titration calorimetry (ITC) revealed that S13 bound CK2α with a dissociation constant (Kd = 600 nM) comparable to that of CAM4066 (350 nM; Figure 1C). This indicated that the exit vector modification and linker installation were well tolerated. Co-crystallisation of S13 with

• suitable for linker installation, and introduction of a secondary amine at this position provided a versatile handle for downstream functionalisation. The resulting CAM4066-derived ligand–linker analogue S13 retained high-affinity binding to CK2α and preserved the characteristic bivalent binding mode in co