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1.
J Med Chem ; 67(7): 5168-5184, 2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38549449

ABSTRACT

Molecules with N-oxide functionalities are omnipresent in nature and play an important role in Medicinal Chemistry. They are synthetic or biosynthetic intermediates, prodrugs, drugs, or polymers for applications in drug development and surface engineering. Typically, the N-oxide group is critical for biomedical applications of these molecules. It may provide water solubility or decrease membrane permeability or immunogenicity. In other cases, the N-oxide has a special redox reactivity which is important for drug targeting and/or cytotoxicity. Many of the underlying mechanisms have only recently been discovered, and the number of applications of N-oxides in the healthcare field is rapidly growing. This Perspective article gives a short summary of the properties of N-oxides and their synthesis. It also provides a discussion of current applications of N-oxides in the biomedical field and explains the basic molecular mechanisms responsible for their biological activity.


Subject(s)
Chemistry, Pharmaceutical , Oxides , Oxides/chemistry , Polymers/chemistry
2.
ChemistryOpen ; : e202300298, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38224205

ABSTRACT

High complex stability and longitudinal relaxivity of Gd-based contrast agents are important requirements for magnetic resonance imaging (MRI) because they ensure patient safety and contribute to measurement sensitivity. Charged and zwitterionic Gd3+ -complexes of the well-known chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) provide an excellent basis for the development of safe and sensitive contrast agents. In this report, we describe the synthesis of DOTA-NOx, a DOTA derivative with four N-oxide functionalities via "click" functionalization of the tetraazide DOTAZA. The resulting complexes Gd-DOTA-NOx and Eu-DOTA-NOx are stable compounds in aqueous solution. NMR-spectroscopic characterization revealed a high excess of the twisted square antiprismatic (TSAP) coordination geometry over square antiprismatic (SAP). The longitudinal relaxivity of Gd-DOTA-NOx was found to be r1 =7.7 mm-1 s-1 (1.41 T, 37 °C), an unusually high value for DOTA complexes of comparable weight. We attribute this high relaxivity to the steric influence and an ordering effect on outer sphere water molecules surrounding the complex generated by the strongly hydrated N-oxide groups. Moreover, Gd-DOTA-NOx was found to be stable against transchelation with high excess of EDTA (200 eq) over a period of 36 h, and it has a similar in vitro cell toxicity as clinically used DOTA-based GBCAs.

3.
Langmuir ; 39(49): 17959-17971, 2023 Dec 12.
Article in English | MEDLINE | ID: mdl-38033196

ABSTRACT

The use of surface-grafted polymer brushes with combined low-fouling and antibacterial functionality is an attractive strategy to fight biofilm formation. This report describes a new styrene derivative combining a quaternary ammonium group with a sulfobetaine group in one monomer. Surface-initiated polymerization of this monomer on titanium and a polyethylene (PE) base material gave bifunctional polymer brush layers. Grafting was achieved via surface-initiated atom transfer radical polymerization from titanium or heat-induced free-radical polymerization from plasma-activated PE. Both techniques gave charged polymer layers with a thickness of over 750 nm, as confirmed by ToF-SIMS-SPM measurements. The chemical composition of the brush polymers was confirmed by XPS and FT-IR analysis. The surface charge, characterized by the ζ potential, was positive at different pH values, and the number of solvent-accessible excess ammonium groups was found to be ∼1016 N+/cm2. This led to strong antibacterial activity against Gram-positive and Gram-negative bacteria that was superior to a structurally related contact-active polymeric quaternary ammonium brush. In addition to this antibacterial activity, good low-fouling properties of the dual-function polymer brushes against Gram-positive and Gram-negative bacteria were found. This dual functionality is most likely due to the combination of antibacterial quaternary ammonium groups with antifouling sulfobetaines. The combination of both groups in one monomer allows the preparation of bifunctional brush polymers with operationally simple polymerization techniques.

4.
Langmuir ; 39(31): 11063-11072, 2023 Aug 08.
Article in English | MEDLINE | ID: mdl-37490748

ABSTRACT

Surface-initiated atom transfer radical polymerization (SI-ATRP) is a powerful tool for grafting functional polymers from metal surfaces. It depends on the immobilization of suitable initiators on the surface before radical polymerization. Herein, we report a set of bifunctional initiators bearing a phosphonic acid group for surface binding and a bromoisobutyramide moiety for SI-ATRP. We have analyzed the impact of the connecting alkyl spacers on the grafting process of (vinylbenzyl)trimethylammonium chloride (VBTAC) from titanium as a base material. The thickness of the grafted polymer increased with the spacer length of the initiator. We obtained chemically stable polycationic surfaces with high charge densities of ∼1016 N+/cm2 leading to efficient contact activity of modified titanium coupons against S. aureus. Notably, SI-ATRP grafting was efficient with VBTAC as a styrene-derived ammonium compound. Thus, the reported protocol avoids post-grafting quaternization with toxic alkylating reagents.

5.
ChemMedChem ; 18(13): e202300112, 2023 07 03.
Article in English | MEDLINE | ID: mdl-37057615

ABSTRACT

The natural siderophore desferrioxamine B (DFOB) has been used for targeted PET imaging with 89 Zr before. However, Zr-DFOB has a limited stability and a number of derivatives have been developed with improved chelation properties for zirconium. We describe the synthesis of pseudopeptidic analogues of DFOB with azido side chains. These are termed AZA-DFO (hexadentate) and AZA-DFO* (octadentate) and are assembled via a modular synthesis from Orn-ß-Ala and Lys-ß-Ala. Nine different chelators have been conjugated to zwitterionic moieties by copper-catalyzed azide-alkyne cycloaddition (CuAAC). The resulting water-soluble chelators form Zr complexes under mild conditions (room temperature for 90 min). Transchelation assays with 1000-fold excess of EDTA and 300-fold excess of DFOB revealed that a short spacing of hydroxamates in (Orn-ß-Ala)3-4 leads to improved complex stability compared to a longer spacing in (Lys-ß-Ala)3-4 . We found that the alignment of amide groups in the pseudopeptide backbone and the presence of zwitterionic sidechains did not compromise the stability of the Zr-complexes with our chelators. We believe that the octadentate derivative AZA-DFO* is particularly valuable for the preparation of new Zr-chelators for targeted imaging which combine tunable pharmacokinetic properties with high complex stability and fast Zr-complexation kinetics.


Subject(s)
Deferoxamine , Radioisotopes , Deferoxamine/chemistry , Radioisotopes/chemistry , Zirconium/chemistry , Chelating Agents/chemistry , Positron-Emission Tomography/methods
6.
Amino Acids ; 55(5): 665-678, 2023 May.
Article in English | MEDLINE | ID: mdl-36894750

ABSTRACT

We present alkali salts of amino acids as functional, non-toxic, non-hazardous, non-volatile, chemically stable, and cheap alkaline additives for common acidic corrosion inhibitors. The resulting mixtures have been evaluated for Co, Ni, and Cu leaching and were analyzed by chip filter assay, potentiodynamic polarization measurements, electrochemical impedance measurements, and gravimetry for corrosion protection of iron and steel in aqueous environment at slightly alkaline pH. Leaching of Co and Ni was found to depend on the corresponding complex stabilities. Taurine (Tau) as well as aminohexanoic acid (AHX) leads to low leaching of Co and Ni. Particularly AHX is an attractive low leaching additive leading to lower Co and Ni concentrations in solution than currently used amino alcohols. Glu and Tau were found to synergistically interact with several acidic corrosion inhibitors of the carboxylic acid and the phosphonic acid type. Tau had a particularly positive impact on the protective properties of carboxyphosphonic acids. Glu had also a positive effect on the anti-corrosive properties of several acidic corrosion inhibitors and served as an anti-scalant. Alkali salts of Glu and Tau might thus serve as commercially and ecologically attractive substitutes for current alkaline additives to acidic corrosion inhibitors.


Subject(s)
Amino Acids , Salts , Corrosion , Alkalies , Steel/chemistry , Taurine
7.
Colloids Surf B Biointerfaces ; 224: 113195, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36758459

ABSTRACT

Zwitterionic polymer brushes were grafted from bulk polyethylene (PE) by air plasma activation of the PE surface followed by radical polymerization of the zwitterionic styrene derivative (vinylbenzyl)sulfobetaine (VBSB). Successful formation of dense poly-(VBSB)-brush layers was confirmed by goniometry, IR spectroscopy, XPS and ToF-SIMS analysis. The resulting zwitterionic layers are about 50-100 nm thick and cause extremely low contact angles of 10° (water) on the material. Correspondingly we determined a high density of > 1.0 × 1016 solvent accessible zwitterions/cm2 (corresponding to 2,0 *10-8 mol/cm2) by a UV-based ion-exchange assay with crystal violet. The elemental composition as determined by XPS and characteristic absorption bands in the IR spectra confirmed the presence of zwitterionic sulfobetaine polymer brushes. The antifouling properties of the resulting materials were evaluated in a bacterial adhesion test against gram-positive bacteria (S. aureus). We observed significantly reduced cellular adhesion of the zwitterionic material compared to pristine PE. These microbiological tests were complemented by tests in natural seawater. During a test period of 21 days, confocal microscopy revealed excellent antifouling properties and confirmed the operating antifouling mechanism. The procedure reported herein allows the efficient surface modification of bulk PE with zwitterionic sulfobetaine polymer brushes via a scalable approach. The resulting modified PE retains important properties of the bulk material and has excellent and durable antifouling properties.


Subject(s)
Biofouling , Polyethylene , Biofouling/prevention & control , Polymerization , Staphylococcus aureus , Polymers/pharmacology , Polymers/chemistry , Surface Properties
8.
Molecules ; 27(6)2022 Mar 08.
Article in English | MEDLINE | ID: mdl-35335142

ABSTRACT

Organic acids, typically derived from an oil-based value chain, are frequently used as corrosion inhibitors in industrial metal working fluids. The criteria for selection of these corrosion inhibitors have changed in the last decades, and are today not only performance-driven, but influenced by ecological considerations, toxicity and regulatory standards. We present scalable semisynthetic approaches to organic corrosion inhibitors based on phosphonic acids from renewable resources. They have been evaluated by chip filter assay, potentiodynamic polarization measurements, electrochemical impedance measurements and gravimetry for corrosion protection of iron and steel in an aqueous environment at slightly alkaline pH. The efficacy of several phosphonic acids tested was found to be strongly dependent on structural features influencing molecular self-assembly of protective layers, and the solubility of salts formed with di- and trivalent cations from the media or formed during corrosion. A carboxyphosphonic acid (derived from castor oil) was found to have remarkable anticorrosive effects in all media tested. We attribute the anticorrosion properties of this carboxyphosphonic acid to the formation of particularly stable protective layers on the metal surface. It might thus serve as a commercially attractive substitute for current acidic corrosion inhibitors, derived from renewable resources.


Subject(s)
Biological Products , Steel , Biological Products/pharmacology , Corrosion , Iron , Phosphorous Acids , Steel/chemistry
9.
Int J Mol Sci ; 22(7)2021 Apr 01.
Article in English | MEDLINE | ID: mdl-33916283

ABSTRACT

Quantitative cellular in vitro nanoparticle uptake measurements are possible with a large number of different techniques, however, all have their respective restrictions. Here, we demonstrate the application of synchrotron-based X-ray fluorescence imaging (XFI) on prostate tumor cells, which have internalized differently functionalized gold nanoparticles. Total nanoparticle uptake on the order of a few hundred picograms could be conveniently observed with microsamples consisting of only a few hundreds of cells. A comparison with mass spectroscopy quantification is provided, experimental results are both supported and sensitivity limits of this XFI approach extrapolated by Monte-Carlo simulations, yielding a minimum detectable nanoparticle mass of just 5 pg. This study demonstrates the high sensitivity level of XFI, allowing non-destructive uptake measurements with very small microsamples within just seconds of irradiation time.


Subject(s)
Gold , Nanoparticles , Optical Imaging , Spectrometry, X-Ray Emission , Humans , Tumor Cells, Cultured
10.
ACS Nano ; 15(3): 3754-3807, 2021 03 23.
Article in English | MEDLINE | ID: mdl-33650433

ABSTRACT

X-ray-based analytics are routinely applied in many fields, including physics, chemistry, materials science, and engineering. The full potential of such techniques in the life sciences and medicine, however, has not yet been fully exploited. We highlight current and upcoming advances in this direction. We describe different X-ray-based methodologies (including those performed at synchrotron light sources and X-ray free-electron lasers) and their potentials for application to investigate the nano-bio interface. The discussion is predominantly guided by asking how such methods could better help to understand and to improve nanoparticle-based drug delivery, though the concepts also apply to nano-bio interactions in general. We discuss current limitations and how they might be overcome, particularly for future use in vivo.


Subject(s)
Nanoparticles , Synchrotrons , Lasers , Radiography , X-Rays
11.
Cell Signal ; 82: 109953, 2021 06.
Article in English | MEDLINE | ID: mdl-33600948

ABSTRACT

Hyperglycemia enhancing the intracellular levels of reactive oxygen species (ROS) contributes to dysfunction and progressive loss of beta cells and thereby to diabetes mellitus. The oxidation sensitive calcium/calmodulin dependent phosphatase calcineurin promotes pancreatic beta cell function and survival whereas the dual leucine zipper kinase (DLK) induces apoptosis. Therefore, it was studied whether calcineurin interferes with DLK action. In a beta cell line similar concentrations of H2O2 decreased calcineurin activity and activated DLK. DLK interacted via its φLxVP motif (aa 362-365) with the interface of the calcineurin subunits A and B. Mutation of the Val prevented this protein protein interaction, hinting at a distinct φLxVP motif. Indeed, mutational analysis revealed an ordered structure of DLK's φLxVP motif whereby Val mediates the interaction with calcineurin and Leu maintains an enzymatically active conformation. Overexpression of DLK wild-type but not the DLK mutant unable to bind calcineurin diminished calcineurin-induced nuclear localisation of the nuclear factor of activated T-cells (NFAT), suggesting that both, DLK and NFAT compete for the substrate binding site of calcineurin. The calcineurin binding-deficient DLK mutant exhibited increased DLK activity measured as phosphorylation of the downstream c-Jun N-terminal kinase, inhibition of CRE-dependent gene transcription and induction of apoptosis. These findings show that calcineurin interacts with DLK; and inhibition of calcineurin increases DLK activity. Hence, this study demonstrates a novel mechanism regulating DLK action. These findings suggest that ROS through inhibition of calcineurin enhance DLK activity and thereby lead to beta cell dysfunction and loss and ultimately diabetes mellitus.


Subject(s)
Calcineurin/metabolism , Insulin-Secreting Cells , MAP Kinase Kinase Kinases/metabolism , Reactive Oxygen Species/metabolism , Animals , Apoptosis , Cell Line , Cricetinae , Insulin-Secreting Cells/cytology , Insulin-Secreting Cells/metabolism , Protein Binding
12.
Colloids Surf B Biointerfaces ; 186: 110679, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31810045

ABSTRACT

Polyethylene (PE) foils were modified with potent contact-active antibacterial quaternary ammonium salts (QAS) by an atmospheric air plasma activation step, followed by graft-polymerisation of vinylbenzyltrimethylammonium chloride (VBTAC) monomers. The presented approach uses a cost efficient air plasma activation and subsequent radical polymerisation in highly concentrated aqueous monomer solutions to generate efficient antibacterial materials. The obtained contact-active poly-VBTAC modified PE foils feature a homogeneous and 300 nm thick polymer layer with a high charge density of approximately 1016 N+/cm2. The antibacterial properties were evaluated against Gram-negative (P. aeruginosa, E. coli) and Gram-positive (S. aureus, S. epidermidis) bacteria. The materials showed strong antibacterial activity by eradicating all the inoculated bacteria with bacterial challenges of 104 to 105 CFU/cm2 and good reductions even at maximum challenge (108 CFU/cm2). We have confirmed contact-activity by an agar diffusion assay. The obtained materials are therefore highly attractive for applications, for example, in packaging and are a contribution to an ecomic and green antimicrobial management without release of biocides to the environment.


Subject(s)
Anti-Bacterial Agents/pharmacology , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , Polyethylene/chemistry , Polystyrenes/chemistry , Quaternary Ammonium Compounds/pharmacology , Air , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Atmospheric Pressure , Microbial Sensitivity Tests , Particle Size , Polymerization , Quaternary Ammonium Compounds/chemical synthesis , Quaternary Ammonium Compounds/chemistry , Salts/chemical synthesis , Salts/chemistry , Salts/pharmacology , Surface Properties
13.
J Med Chem ; 62(23): 10912-10918, 2019 12 12.
Article in English | MEDLINE | ID: mdl-31714783

ABSTRACT

The development of novel prostate-specific membrane antigen (PSMA)-targeted radioactive theranostic agents is currently limited to facilities capable of working with high-energy radioisotopes. Even preselection of lead structures in vitro relies mostly on radioactive assays with PSMA(+) LNCaP and PSMA(-) PC-3 cells. Assays utilizing radioisotopes are time consuming, costly, and limit discovery to a small group of scientists with special facilities. Nonradioactive alternatives are therefore needed in the field. In this paper, we describe an inductively coupled plasma mass spectrometry (ICP-MS)-based method for the evaluation of PSMA-targeting ligands conjugated to DOTA-chelates of Europium. This method is based on LNCaP and PC-3 cells and has been validated with the well-established targeting ligand PSMA-617.


Subject(s)
Antigens, Surface/chemistry , Europium/chemistry , Glutamate Carboxypeptidase II/chemistry , Prostatic Neoplasms/immunology , Biological Assay , Cell Line, Tumor , Humans , Male , Prostatic Neoplasms/diagnosis , Sensitivity and Specificity , Spectrophotometry, Atomic
14.
Chemistry ; 24(72): 19373-19385, 2018 Dec 20.
Article in English | MEDLINE | ID: mdl-30295350

ABSTRACT

Herein, the chemical synthesis and binding analysis of functionalizable rigid and flexible core trivalent sialosides bearing oligoethylene glycol (OEG) spacers interacting with spike proteins of influenza A virus (IAV) X31 is described. Although the flexible Tris-based trivalent sialosides achieved micromolar binding constants, a trivalent binder based on a rigid adamantane core dominated flexible tripodal compounds with micromolar binding and hemagglutination inhibition constants. Simulation studies indicated increased conformational penalties for long OEG spacers. Using a systematic approach with molecular modeling and simulations as well as biophysical analysis, these findings emphasize on the importance of the scaffold rigidity and the challenges associated with the spacer length optimization.


Subject(s)
Influenza A virus/drug effects , Sialic Acids/chemistry , Antiviral Agents/chemistry , Antiviral Agents/metabolism , Antiviral Agents/pharmacology , Humans , Influenza, Human/drug therapy , Influenza, Human/virology , Protein Binding , Sialic Acids/metabolism , Sialic Acids/pharmacology , Structure-Activity Relationship
15.
Macromol Biosci ; 15(12): 1673-8, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26332285

ABSTRACT

Zwitterionic thin films containing α-amino phosphonic acid moieties were successfully introduced on silicon surfaces and their antifouling properties were investigated. Initially, the substrates were modified with a hybrid polymer, composed of poly(methylsilsesquioxane) (PMSSQ) and poly(4-vinyl benzaldehyde) (PStCHO). Next, a Kabachnik-Fields post-polymerization modification (sur-KF-PMR) of the functionalized aldehyde surfaces was conducted with different amines and dialkyl phosphonates. After subsequent deprotection reaction of dialkyl phosphonates, the obtained zwitterionic surfaces were characterized by various techniques and we found excellent antifouling properties of the resulting films.


Subject(s)
Organosilicon Compounds/chemistry , Phosphorous Acids/chemistry , Polymers/chemistry , Silicon/chemistry , Staphylococcus epidermidis/growth & development
16.
Beilstein J Org Chem ; 11: 678-86, 2015.
Article in English | MEDLINE | ID: mdl-26124871

ABSTRACT

A common approach to generate tailored materials and nanoparticles (NPs) is the formation of molecular monolayers by chemisorption of bifunctional anchor molecules. This approach depends critically on the choice of a suitable anchor group. Recently, bifunctional catecholates, inspired by mussel-adhesive proteins (MAPs) and bacterial siderophores, have received considerable interest as anchor groups for biomedically relevant metal surfaces and nanoparticles. We report here the synthesis of new tripodal catecholates as multivalent anchor molecules for immobilization on metal surfaces and nanoparticles. The tripodal catecholates have been conjugated to various effector molecules such as PEG, a sulfobetaine and an adamantyl group. The potential of these conjugates has been demonstrated with the immobilization of tripodal catecholates on ZnO NPs. The results confirmed a high loading of tripodal PEG-catecholates on the particles and the formation of stable PEG layers in aqueous solution.

17.
PLoS One ; 9(11): e113932, 2014.
Article in English | MEDLINE | ID: mdl-25415429

ABSTRACT

SCOPE: Celiac disease is an autoimmune disorder caused by failure of oral tolerance against gluten in genetically predisposed individuals. The epithelial translocation of gluten-derived gliadin peptides is an important pathogenetic step; the underlying mechanisms, however, are poorly understood. Thus, we investigated the degradation and epithelial translocation of two different gliadin peptides, the toxic P31-43 and the immunogenic P56-68. As the size, and hence, the molecular weight of peptides might have an effect on the transport efficiency we chose two peptides of the same, rather short chain length. METHODS AND RESULTS: Fluorescence labeled P31-43 and P56-68 were synthesized and studied in a transwell system with human enterocytes. Fluorometric measurements were done to reveal antigen translocation and flow cytometry as well as confocal microscopy were used to investigate cellular uptake of peptides. Structural changes of these peptides were analysed by MALDI-TOF-MS. According to fluorescence intensities, significantly more P31-43 compared to P56-68 was transported through the enterocyte layer after 24 h incubation. In contrast to previous reports, however, mass spectrometric data do not only show a time-dependent cleavage of the immunogenic P56-68, but we observed for the first time the degradation of the toxic peptide P31-43 at the apical side of epithelial cells. CONCLUSION: Considering the degradation of gliadin peptides by enterocytes, measurement of fluorescence signals do not completely represent translocated intact gliadin peptides. From our experiments it is obvious that even short peptides can be digested prior to the translocation across the epithelial barrier. Thus, the chain length and the sensibility to degradations of gliadin peptides as well as the integrity of the epithelial barrier seem to be critical for the uptake of gliadin peptides and the subsequent inflammatory immune response.


Subject(s)
Enterocytes/metabolism , Gliadin/pharmacokinetics , Gliadin/toxicity , Peptide Fragments/pharmacokinetics , Peptide Fragments/toxicity , Caco-2 Cells , Celiac Disease/immunology , Celiac Disease/metabolism , Celiac Disease/pathology , Enterocytes/immunology , Enterocytes/pathology , Humans , Protein Transport/drug effects
18.
J Org Chem ; 79(21): 10123-31, 2014 Nov 07.
Article in English | MEDLINE | ID: mdl-25303120

ABSTRACT

Terpenoid spiroethers are abundant natural flavors with significant impact, particularly in the food industry. We present in this article the synthesis of new derivatives of the well-known flavors theaspirane and vitispirane using a variant of the Prins cyclization starting from α,ß-unsaturated or heterocyclic ketones. When aromatic ketones were used as the starting materials for Lewis acid-mediated cyclizations, an alternative pathway involving a domino sequence of Prins cyclization, followed by an intramolecular Friedel-Crafts alkylation, gave benzoannelated oxabicyclo[3.3.1]nonane derivatives. Different reaction pathways may be triggered by the reaction temperature to give with good selectivity either tetrahydropyran derivatives as conventional Prins products or oxabicyclo[3.3.1]nonane derivatives.


Subject(s)
Bridged Bicyclo Compounds, Heterocyclic/chemical synthesis , Heterocyclic Compounds/chemical synthesis , Terpenes/chemistry , Bridged Bicyclo Compounds, Heterocyclic/chemistry , Catalysis , Cyclization , Ethers, Cyclic , Heterocyclic Compounds/chemistry , Ketones/chemistry , Molecular Structure , Spiro Compounds
19.
Chembiochem ; 15(16): 2450-7, 2014 Nov 03.
Article in English | MEDLINE | ID: mdl-25209734

ABSTRACT

Carbohydrates are involved in a wide range of biological processes of pharmaceutical relevance. The selective recognition of carbohydrates is therefore of great interest in biology and medicine. In this study we present the synthesis of fluorescent multimeric benzoboroxoles and the analysis of multivalent binding processes to immobilized carbohydrate arrays by fluorescence spectroscopy. We observed high binding affinities of trimeric benzoboroxoles by determination of KDsurf values for their interaction with α-Gal on glass chips. The observed KDsurf values were in the mid-nM range (49 and 104 nM) and are comparable to the KDsurf values for binding of natural lectins, such as that of ConA to immobilized α-Man (79 nM). The array technology was found to be an excellent tool for studying the binding processes of multivalent lectin mimetics with respect to profiling and quantitation.


Subject(s)
Boronic Acids/chemistry , Carbohydrates/chemistry , Lectins/metabolism , Kinetics , Lectins/chemistry , Microarray Analysis , Protein Binding , Spectrometry, Fluorescence
20.
J Chromatogr A ; 1363: 270-7, 2014 Oct 10.
Article in English | MEDLINE | ID: mdl-25042438

ABSTRACT

Chiral spirocyclic terpenoids are abundant natural flavors with significant impact particularly on the food industry. Chromatographic methods for analytical and preparative separation of these compounds are therefore of high interest to natural product chemists in academia and industry. Gas chromatography on chiral stationary phases is currently the standard method for the separation of volatile terpenoids, limiting the scale to analytical quantities. We report herein high performance liquid chromatography (HPLC) and supercritical fluid chromatography (SFC) protocols for the chiral separation of several racemic spirocyclic terpenoids such as the important flavors theaspirane and vitispirane. A screening of mobile phases and 16 commercially available chiral stationary phases (CSPs) largely based on polysaccharides led to identification of protocols for the separation of all terpenoids tested. SFC methods were found to be particularly useful for the separation of these spirocyclic flavors due to the volatility and low polarity of the compounds. The reported chiral HPLC and SFC protocols are scalable alternatives to gas chromatographic separations of volatile terpenoid flavors.


Subject(s)
Chromatography, High Pressure Liquid/methods , Chromatography, Supercritical Fluid/methods , Terpenes/analysis , Stereoisomerism
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