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

Orthogonal photoswitching of heterobivalent azobenzene glycoclusters: the effect of glycoligand orientation in bacterial adhesion

• Leon M. Friedrich and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2025, 21, 736–748, doi:10.3762/bjoc.21.57

• space and additionally, secondary interactions exerted by multivalent glycoligands have an effect on affinity. A recently introduced orthogonally photoswitchable heterobivalent azobenzene Glc/Man glycocluster was utilized to examine these aspects of carbohydrate recognition in a bacterial adhesion

Photoswitchable glycoligands targeting Pseudomonas aeruginosa LecA

• Yu Fan,
• Ahmed El Rhaz,
• Stéphane Maisonneuve,
• Emilie Gillon,
• Maha Fatthalla,
• Franck Le Bideau,
• Guillaume Laurent,
• Samir Messaoudi,
• Anne Imberty and
• Juan Xie

Beilstein J. Org. Chem. 2024, 20, 1486–1496, doi:10.3762/bjoc.20.132

• , with Kd values from micromolar (for monovalent galactosides) to nanomolar range (for di- and multivalent derivatives) [5][6][7][8]. For the monovalent system, it has been shown that aromatic aglycons favored “T-shaped” CH...π interactions with the protons of the His50 imidazole in the carbohydrate

Auxiliary strategy for the general and practical synthesis of diaryliodonium(III) salts with diverse organocarboxylate counterions

• Naoki Miyamoto,
• Daichi Koseki,
• Kohei Sumida,
• Elghareeb E. Elboray,
• Naoko Takenaga,
• Ravi Kumar and
• Toshifumi Dohi

Beilstein J. Org. Chem. 2024, 20, 1020–1028, doi:10.3762/bjoc.20.90

• conditions afforded the ditrigger iodonium salt 4l in 88% yield, demonstrating the versatility of the process for the synthesis of multivalent precursors. Furthermore, phenyliodine(III) bis(trifluoroacetate) was used as a starting material under the optimized reaction conditions and the corresponding phenyl

Elucidating the glycan-binding specificity and structure of Cucumis melo agglutinin, a new R-type lectin

• Jon Lundstrøm,
• Emilie Gillon,
• Valérie Chazalet,
• Nicole Kerekes,
• Antonio Di Maio,
• Ten Feizi,
• Yan Liu,
• Annabelle Varrot and
• Daniel Bojar

Beilstein J. Org. Chem. 2024, 20, 306–320, doi:10.3762/bjoc.20.31

• , Supporting Information File 2), supporting our ITC and SPR data where no multivalent binding effects were observed for the single-domain N-terminal construct. In the GalNAc-complexed structure (PDB ID 8R8C) [30], the N-acetyl group of GalNAc extended beyond C2 into the cavity noted in the LacNAc complex

One-pot nucleophilic substitution–double click reactions of biazides leading to functionalized bis(1,2,3-triazole) derivatives

• Hans-Ulrich Reissig and
• Fei Yu

Beilstein J. Org. Chem. 2023, 19, 1399–1407, doi:10.3762/bjoc.19.101

• these results [37][38]. For several years, our group was interested in preparing multivalent carbohydrate mimetics [39][40][41][42][43] on the basis of efficient coupling reactions of aminopyran and aminooxepane derivatives with suitable linker elements. Hence, the aminopyran derivatives A could be

• converted into several multivalent compounds B by amine or amide bond formations [44][45][46][47]. The transformation of the corresponding azidopyrans and azidooxepanes C or E into multivalent 1,2,3-triazole derivatives D and F by Meldal–Sharpless cycloadditions with suitable alkynes proceeded generally in

• good yields and furnished another set of multivalent carbohydrate mimetics [48][49][50]. In the current report, we want to disclose our experience with an “inverted” approach to multivalent systems [51]: bicyclic 1,2-oxazine derivatives of type G [52][53], which can be regarded as internally protected

Computational model predicts protein binding sites of a luminescent ligand equipped with guanidiniocarbonyl-pyrrole groups

• Neda Rafieiolhosseini,
• Matthias Killa,
• Thorben Neumann,
• Niklas Tötsch,
• Jean-Noël Grad,
• Alexander Höing,
• Thies Dirksmeyer,
• Jochen Niemeyer,
• Christian Ottmann,
• Shirley K. Knauer,
• Michael Giese,
• Jens Voskuhl and
• Daniel Hoffmann

Beilstein J. Org. Chem. 2022, 18, 1322–1331, doi:10.3762/bjoc.18.137

• individual GCP or lysine groups with 14-3-3ζ. To model the interactions of 14-3-3ζ with the full multivalent 1 ligand, we have combined these and further interactions in a single model as described in the following. Coarse-grained model We developed a coarse-grained model of 1 known as the Bead-Spring model

Constrained thermoresponsive polymers – new insights into fundamentals and applications

• Patricia Flemming,
• Alexander S. Münch,
• Andreas Fery and
• Petra Uhlmann

Beilstein J. Org. Chem. 2021, 17, 2123–2163, doi:10.3762/bjoc.17.138

• counterions, multivalent ions exert a particularly strong influence on polyelectrolytes due to their high charge density [292]. Plamper et al. [293] as well as Zhang et al. [294] demonstrated that in the presence of the triply negatively charged hexacyanoferrate [Fe(CN)6]3−, polycationic poly

• (dimethylaminoethyl methacrylate) (PDMAEMA) exhibits UCST behavior in aqueous solution. This is particularly interesting since the polymer initially exhibits LCST behavior in the absence of multivalent ions due to its amphiphilic polymer structure [295][296]. The switchable thermoresponsivity is furthermore

Multiswitchable photoacid–hydroxyflavylium–polyelectrolyte nano-assemblies

• Alexander Zika and
• Franziska Gröhn

Beilstein J. Org. Chem. 2021, 17, 166–185, doi:10.3762/bjoc.17.17

• addition of a fifth hydroxy group, more binding sites become available for the association with the poly(allylamine), leading to an increase in assembly size: More multivalent small molecules bind to the polyelectrolyte, interconnecting more polyelectrolyte molecules into larger aggregates. At the same

Supramolecular polymerization of sulfated dendritic peptide amphiphiles into multivalent L-selectin binders

• David Straßburger,
• Svenja Herziger,
• Katharina Huth,
• Moritz Urschbach,
• Rainer Haag and
• Pol Besenius

Beilstein J. Org. Chem. 2021, 17, 97–104, doi:10.3762/bjoc.17.10

• of rigid supramolecular polymers. Since multivalent sulfated supramolecular structures mimic naturally occurring L-selectin ligands, the corresponding affinity was evaluated using a competitive SPR binding assay and benchmarked to an ethylene glycol-decorated supramolecular polymer. Keywords: L

• , these interactions occur in a multivalent fashion, allowing to overcome drawbacks of the limited strength of noncovalent bonds and to tune the selectivity at the same time [1][2]. The binding of viruses to the membrane of their host cells [3][4][5] as well as the recognition of carbohydrates by lectins

• [6][7][8][9] are only few of the numerous examples for multivalent protein–protein or protein–carbohydrate interactions that underline their pivotal role in biology. Mimicking polyvalency using synthetic systems has therefore become a growing field and the high degree of functionality renders

Using multiple self-sorting for switching functions in discrete multicomponent systems

• Amit Ghosh and
• Michael Schmittel

Beilstein J. Org. Chem. 2020, 16, 2831–2853, doi:10.3762/bjoc.16.233

• hand denotes the formation of a single entity from all constituents using orthogonal binding motifs. In the self-sorting of more than two components, thus at least one ligand has to be multivalent (Figure 2). Clearly, heteromeric self-sorting has a superior value for switching because it allows for

Selective recognition of ATP by multivalent nano-assemblies of bisimidazolium amphiphiles through “turn-on” fluorescence response

• Rakesh Biswas,
• Surya Ghosh,
• Shubhra Kanti Bhaumik and
• Supratim Banerjee

Beilstein J. Org. Chem. 2020, 16, 2728–2738, doi:10.3762/bjoc.16.223

• presence of positive surface charges on the multivalent aggregates led to ATP binding which was accompanied by a significant increase in the excimeric emission intensity. This provided a convenient way of monitoring ATP binding in a “turn-on” mode and an efficient detection of ATP was achieved in aqueous

• buffer and also in buffer containing 150 mM NaCl at physiological pH value. Furthermore, the multivalent aggregates demonstrated a significant selectivity in ATP detection over ADP, AMP and pyrophosphate. Keywords: amphiphile; ATP; excimer; multivalency; self-assembly; Introduction Supramolecular anion

• the receptor with their complementary binding partners in the target analyte [15]. One of the ways to design multivalent systems is to connect the receptors through covalent linkages. Conjugated polymers and conjugated polymer electrolytes are prominent examples of covalently constructed multivalent

Optical detection of di- and triphosphate anions with mixed monolayer-protected gold nanoparticles containing zinc(II)–dipicolylamine complexes

• Lena Reinke,
• Julia Bartl,
• Marcus Koch and
• Stefan Kubik

Beilstein J. Org. Chem. 2020, 16, 2687–2700, doi:10.3762/bjoc.16.219

• preferred binding mode of zinc(II)–dipicolylamine complexes with phosphate anions which involves binding of the anion between two metal centers. This work thus provided information on how the behavior of mixed monolayer-protected gold nanoparticles is affected by multivalent interactions, at the same time

• other serves to dilute the receptor units on the surface to such an extent that analyte binding to units residing on the same nanoparticle becomes unlikely. The number of receptors should still be high enough to allow nanoparticle crosslinking to benefit from multivalent interactions [19][20][21]. The

• concentration window, in which there was a relatively sharp transition from the dissolved to the aggregated state. This behavior could be attributed to the multivalent nature of the AuNPs that caused nanoparticle crosslinking to benefit from cooperative effects of the surface-bound receptor units [19][20][21

NMR Spectroscopy of supramolecular chemistry on protein surfaces

• Peter Bayer,
• Anja Matena and
• Christine Beuck

Beilstein J. Org. Chem. 2020, 16, 2505–2522, doi:10.3762/bjoc.16.203

• combination of two or more GCP moieties with variable linkers enables the construction of multivalent ligands geared towards a specific spot on protein surface, which by design can lead to either stabilization [42][43][44][45] or inhibition [46] of a given protein–protein interaction. The inhibition of the

• multivalent ligands, like multi-armed GCP ligands with flexible scaffolds or nanoparticles, have been published yet. NMR spectroscopy is the ideal method to gain structural information and identify residues involved in ligand binding because it delivers single-residue resolution. It is also suitable to

• binding of tweezers to the intrinsically disordered protein (IDP) tau was studied by 1H,15N-HSQC titrations using specific labeling of lysine residues [81], which will be described in the section ‘Specific amino acid labeling’. Multivalent GCP ligands have been successfully tailored to stabilize the

Synthesis of Streptococcus pneumoniae serotype 9V oligosaccharide antigens

• Sharavathi G. Parameswarappa,
• Claney L. Pereira and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2020, 16, 1693–1699, doi:10.3762/bjoc.16.140

• developing countries [3]. With increasing antimicrobial resistance to antibiotics, vaccines are becoming even more important to control these pathogens. Despite the availability of multivalent polysaccharide and glycoconjugate vaccines such as Pneumovax, Prevnar® 13, and Synflorix, pneumonococcal diseases

1,2,3-Triazolium macrocycles in supramolecular chemistry

• Mastaneh Safarnejad Shad,
• Pulikkal Veettil Santhini and
• Wim Dehaen

Beilstein J. Org. Chem. 2019, 15, 2142–2155, doi:10.3762/bjoc.15.211

• interactions such as hydrogen bonding, π–π stacking, electrostatic interactions, van der Waals forces, hydrophobic/solvatophobic effects and coordination bonds [2][3]. Advances in supramolecules from molecular to macroscopic size with pre-structured or functionalized receptors and multivalent binding positions

• reduced cavity. These conformational changes are reversible in solution with switching pH. 4.3. A multivalent catenane and its motion in diverse pH media Cell signaling, energy transduction, and cargo delivery are some of functions of very complicatedly assembled biomolecular machines. Multivalent

• interactions, compared to monovalent receptor–ligand interactions offer the advantage of multiple and sequential binding within the host–guest systems. These noncovalent interactions which can be controlled in a chemical or physical manner depend on the binding sites in the multivalent assembly [67

Multiple threading of a triple-calix[6]arene host

• Veronica Iuliano,
• Roberta Ciao,
• Emanuele Vignola,
• Carmen Talotta,
• Patrizia Iannece,
• Margherita De Rosa,
• Annunziata Soriente,
• Carmine Gaeta and
• Placido Neri

Beilstein J. Org. Chem. 2019, 15, 2092–2104, doi:10.3762/bjoc.15.207

• directed towards the study of multiple-threading processes of host systems bearing multiple-wheels (multivalent hosts). On this basis, interesting handcuff-like interpenetrated systems (Figure 1) have been reported to date in literature [10][11][12][13][14][15][16], which represent non-trivial

Reversible end-to-end assembly of selectively functionalized gold nanorods by light-responsive arylazopyrazole–cyclodextrin interaction

• Maximilian Niehues,
• Patricia Tegeder and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2019, 15, 1407–1415, doi:10.3762/bjoc.15.140

• thiols by a known two-step synthesis [42][43] to give a multivalent ligand (tCD) that is tightly bound to the gold surface and is not replaced by an excess of monothiolated tetraethylene glycol (tTEG). It is important to note the importance of the addition of ethanol during the ligand exchange to

Host–guest interactions between p-sulfonatocalix[4]arene and p-sulfonatothiacalix[4]arene and group IA, IIA and f-block metal cations: a DFT/SMD study

• Valya K. Nikolova,
• Cristina V. Kirkova,
• Silvia E. Angelova and
• Todor M. Dudev

Beilstein J. Org. Chem. 2019, 15, 1321–1330, doi:10.3762/bjoc.15.131

• are not as good as those of other common macrocycles. Two positions (phenolic OH groups and p-positions) in the calixarenes’ structure can be easily modified by subsequent reactions [4]. As a result, calixarenes have a great potential as simple scaffolds to build molecular receptors and multivalent

A chemically contiguous hapten approach for a heroin–fentanyl vaccine

• Yoshihiro Natori,
• Candy S. Hwang,
• Lucy Lin,
• Lauren C. Smith,
• Bin Zhou and
• Kim D. Janda

Beilstein J. Org. Chem. 2019, 15, 1020–1031, doi:10.3762/bjoc.15.100

• into several immunochemical questions including: (1) the impact of multivalent hapten scaffolding; (2) the influence on increasing hapten density as compared to successive hapten-conjugations and (3) how concomitant hapten-presentation would impact immune response to each drug [15]. Herein, we describe

Towards the preparation of synthetic outer membrane vesicle models with micromolar affinity to wheat germ agglutinin using a dialkyl thioglycoside

• Dimitri Fayolle,
• Nathalie Berthet,
• Bastien Doumeche,
• Olivier Renaudet,
• Peter Strazewski and
• Michele Fiore

Beilstein J. Org. Chem. 2019, 15, 937–946, doi:10.3762/bjoc.15.90

• affinities to GlcNAc [31]. The proximity of adjacent binding sites (≈14 Å) [32] makes this lectin an excellent candidate to investigate multivalent carbohydrate–protein interactions [33]. Although the scientific literature is rich of remarkable examples of biologically active carbohydrate-based compounds

• compounds similar to other efficient multivalent glycoconjugates obtained by TEC of sugar thiols with different multivalent scaffolds such as octasilsesquioxanes [35], cyclopeptides [36][37] and polymers [38]. Both compounds 5 and 8 showed low IC50 values (a tenth to some hundreds of micromolars) where the

Design and synthesis of multivalent α-1,2-trimannose-linked bioerodible microparticles for applications in immune response studies of Leishmania major infection

• Chelsea L. Rintelmann,
• Tara Grinnage-Pulley,
• Kathleen Ross,
• Daniel E. K. Kabotso,
• Angela Toepp,
• Anne Cowell,
• Christine Petersen,
• Balaji Narasimhan and
• Nicola Pohl

Beilstein J. Org. Chem. 2019, 15, 623–632, doi:10.3762/bjoc.15.58

• study the mechanisms of immune modulation. In this study, a new bioerodible polyanhydride microparticle was designed and conjugated with a glycodendrimer molecular probe. This molecular probe incorporates a pathogen-like multivalent display of α-1,2-trimannose, for which a more efficient synthesis was

• pathogen (1 μm in diameter) and provide a multivalent display of the synthetic α-1,2-trimannose similar to the Leishmania promastigote cell-wall glycans. Furthermore, a tethered fluorophore would allow for immunofluorescence assays, intracellular trafficking, and validation of T cell-mediated antigen

• . From the general design elements in Figure 3, we proposed the following synthetic motifs. For PRR binding, a dendrimeric scaffold provides a multivalent display of the α-1,2-trimannose glycoconjugate, similar to Leishmania LPG and additionally may promote glycodendrimer antigen presentation when

Aqueous olefin metathesis: recent developments and applications

• Valerio Sabatino and
• Thomas R. Ward

Beilstein J. Org. Chem. 2019, 15, 445–468, doi:10.3762/bjoc.15.39

• and co-workers led to several biological applications [79][80]. Kiessling and co-workers were the first to use ROMP for the synthesis of biologically active polymers and for the synthesis of multivalent antigens to probe signaling pathways in vivo [81][82]. In 2008, Davis and co-workers performed site

Lectins of Mycobacterium tuberculosis – rarely studied proteins

• Katharina Kolbe,
• Sri Kumar Veleti,
• Norbert Reiling and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2019, 15, 1–15, doi:10.3762/bjoc.15.1

• homodimers, homotrimers, and higher-ordered oligomers, which increases their avidity for multivalent ligands. C-Type lectins play key roles in cell–cell interactions, such as host–pathogen interactions, and phagocytosis [92]. The Mtb gene product of Rv2075c shows partial amino acid sequence similarity to

Pathoblockers or antivirulence drugs as a new option for the treatment of bacterial infections

• Matthew B. Calvert,
• Varsha R. Jumde and
• Alexander Titz

Beilstein J. Org. Chem. 2018, 14, 2607–2617, doi:10.3762/bjoc.14.239

• . Therefore, multivalent display of lectin and ligand results in a higher avidity [22][23]. The Lindhorst group also synthesized and analyzed so-called glycoclusters, e.g., 7 (Figure 1), where the saccharide moiety is displayed in a multivalent fashion [17][24][25][26]. When this simple trimannosylated

• LecA and α-fucosides and mannosides for LecB), numerous multivalent presentations have been developed with the aim to improve affinity based on avidity [22]. LecA recognizes aryl β-D-galactosides with moderate potency, e.g., compound 10 (Figure 2). However, attempts to optimize the potency by varying

• galactoside moieties are optimally oriented in space to simultaneously bind to two of the four binding sites in LecA [41]. This optimal geometric match to LecA resulted in low nanomolar inhibition of LecA. LecB has been studied in detail using multivalent and small molecule approaches. Interestingly, the