- MeSH
- DNA Adducts MeSH
- Cisplatin pharmacology MeSH
- Research Support as Topic MeSH
- Protein Conformation MeSH
- Humans MeSH
- Ligands MeSH
- Models, Molecular MeSH
- Oligonucleotides chemistry MeSH
- Organometallic Compounds pharmacology chemistry MeSH
- HMGB1 Protein chemistry MeSH
- Antineoplastic Agents pharmacology MeSH
- Stereoisomerism MeSH
- Protein Structure, Tertiary MeSH
- Thymine chemistry MeSH
- Protein Binding MeSH
- Binding Sites MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
Polar-ionic and hydro-organic mobile phase mode of high-performance liquid chromatographic separations of 23 sterically constrained primary β(3)-amino acid enantiomers containing, alkyl, aryl or heteroaryl side-chains were carried out by using newly developed Cinchona alkaloid-based zwitterionic chiral selectors and the stationary phases Chiralpak ZWIX(+)™ and ZWIX(-)™. In the polar-ionic mode, the effects of the composition of the bulk solvent and the natures of the co- and counter-ions, while in the hydro-organic mode, the effects of the pH, the counter-ion concentration and the structures of the analytes were investigated. The separations of the enantiomers of these 23 primary β(3)-amino acids, which can be classified as a series of quasi- (pseudo-) homologs, were optimized in both chromatographic modes. The elution sequence was determined in most cases and a reversal of elution order on ZWIX(+)™ and ZWIX(-)™ column was observed. On the basis of this intermolecular recognition model between the selectors and the given enantiomers an indirect assignment of the resolved enantiomer via chromatography is proposed.
The enantiomers of trans-paroxetine were separated on four chiral stationary phases (CSPs) based on chiral zwitterionic Cinchona alkaloids fused with (R,R)- or (S,S)-trans-2-aminocyclohexanesulfonic acid. The enantioseparations were carried out in polar-ionic or in hydro-organic mobile phases with MeOH/THF, MeCN/THF, MeCN/THF/H2O and MeOH/MeCN/THF containing organic acid and base additives, in the temperature range 0-50°C. The effects of the mobile phase composition, the natures and concentrations of the additives and temperature on the separations were investigated. Thermodynamic parameters were calculated from plots of ln α vs 1/T. Δ(ΔH°) ranged between -3.0 and +1.5 kJ mol(-1), and Δ(ΔS°) between -8.8 and +5.9 J mol(-1)K(-1). The enantioseparation was generally enthalpically controlled, the retention factor and separation factor decreasing with increasing temperature, but entropically controlled separation was also observed. The elution sequences of the paroxetine enantiomers on the two pairs of pseudo-enantiomeric CSPs were investigated, and an attempt was made to explain the observed anomalies in silico in order to gain an insight into the underlying molecular recognition events between the four chiral selectors and the analyte enantiomers.
Loss of a base in DNA leading to creation of an abasic (AP) site leaving a deoxyribose residue in the strand, is a frequent lesion that may occur spontaneously or under the action of various physical and chemical agents. Progress in the understanding of the chemistry and enzymology of abasic DNA largely relies upon the study of AP sites in synthetic duplexes. We report here on interactions of diastereomerically pure metallo-helical 'flexicate' complexes, bimetallic triple-stranded ferro-helicates [Fe2(NN-NN)3](4+) incorporating the common NN-NN bis(bidentate) helicand, with short DNA duplexes containing AP sites in different sequence contexts. The results show that the flexicates bind to AP sites in DNA duplexes in a shape-selective manner. They preferentially bind to AP sites flanked by purines on both sides and their binding is enhanced when a pyrimidine is placed in opposite orientation to the lesion. Notably, the Λ-enantiomer binds to all tested AP sites with higher affinity than the Δ-enantiomer. In addition, the binding of the flexicates to AP sites inhibits the activity of human AP endonuclease 1, which is as a valid anticancer drug target. Hence, this finding indicates the potential of utilizing well-defined metallo-helical complexes for cancer chemotherapy.
- MeSH
- 2-Aminopurine analysis MeSH
- Amiloride analysis MeSH
- Nucleic Acid Denaturation MeSH
- DNA Footprinting MeSH
- DNA-(Apurinic or Apyrimidinic Site) Lyase antagonists & inhibitors MeSH
- DNA chemistry MeSH
- Enzyme Inhibitors chemistry MeSH
- Calorimetry MeSH
- DNA Damage * MeSH
- Antineoplastic Agents chemistry MeSH
- Binding Sites MeSH
- Ferrous Compounds chemistry MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
In the enantiomeric separation of highly polar compounds, a traditionally challenging task for high-performance liquid chromatography, ion-exchange chiral stationary phases have found the main field of application. In this contribution, we present a series of novel anion-exchange-type chiral stationary phases for enantiomer separation of protected amino phosphonates and N-protected amino acids. Two of the prepared selectors possessed a double and triple bond within a single molecule. Thus, they were immobilized onto silica support employing either a thiol-ene (radical) or an azide-yne (copper(I)-catalyzed) click reaction. We evaluated the selectivity and the effect of immobilization proceeding either by the double bond of the Cinchona alkaloid or a triple bond of the carbamoyl moiety on the chromatographic performance of the chiral stationary phases using analytes with protecting groups of different size, flexibility, and π-acidity. The previously observed preference toward protecting groups possessing π-acidic units, which is a typical feature of Cinchona-based chiral stationary phases, was preserved. In addition, increasing the bulkiness of the selectors' carbamoyl units leads to significantly reduced retention times, while very high selectivity toward the tested analytes is retained.
The interaction of metallosupramolecular cylinders with DNA three-way junctions has been studied by gel electrophoresis. A recent X-ray crystal structure of a palindromic oligonucleotide forming part of a complex with such a cylinder revealed binding at the heart of a three-way junction structure. The studies reported herein confirm that this is not solely an artefact of crystallisation and reveal that this is a potentially very powerful new mode of DNA recognition with wide scope. The cylinders are much more effective at stabilizing three-way junctions than simple magnesium di-cations or organic or metallo-organic tetra-cations, with the M cylinder enantiomer being more effective than P. The recognition is not restricted to three-way junctions formed from palindromic DNA with a central AT step at the junction; non-palindromic three-way junctions and those with GC steps are also stabilised. The cylinder is also revealed to stabilise other Y-shaped junctions, such as that formed at a fraying point in duplex DNA (for example, a replication fork), and other DNA three-way junction structures, such as those containing unpaired nucleotides, perhaps by opening up this structure to access the central cavity.
Bulged DNA structures are of general biological significance because of their important roles in a number of biochemical processes. Compounds capable of targeting bulged DNA sequences can be used as probes for studying their role in nucleic acid function, or could even have significant therapeutic potential. The interaction of [Fe(2)L(3)](4+) metallosupramolecular helicates (L = C(25)H(20)N(4)) with DNA duplexes containing bulges has been studied by measurement of the DNA melting temperature and gel electrophoresis. This study was aimed at exploring binding affinities of the helicates for DNA bulges of various sizes and nucleotide sequences. The studies reported herein reveal that both enantiomers of [Fe(2)L(3)](4+) bind to DNA bulges containing at least two unpaired nucleotides. In addition, these helicates show considerably enhanced affinity for duplexes containing unpaired pyrimidines in the bulge and/or pyrimidines flanking the bulge on both sides. We suggest that the bulge creates the structural motif, such as the triangular prismatic pocket formed by the unpaired bulge bases, to accommodate the [Fe(2)L(3)](4+) helicate molecule, and is probably responsible for the affinity for duplexes with a varying number of bulge bases. Our results reveal that DNA bulges represent another example of unusual DNA structures recognized by dinuclear iron(II) ([Fe(2)L(3)](4+)) supramolecular helicates.
... in Chiral Discrimination 180 -- 9.1.1 Molecular Recognition of Enantiomers Using Potentiometrie, Enantioselective ... ... Membrane Electrodes 181 -- 9.1.2 Molecular Recognition of Enantiomers Using Amperometric -- Biosensors ... ... 182 -- 9.1.3 Molecular Recognition of Enantiomers Using Immunosensors 183 -- 9.1.4 The Role of Kinetics ... ... in Molecular Recognition of Enantiomers -- Using Electrochemical Sensors 183 -- 9.2 Applications of ... ... 3,3\\5-Triiodo-Thyronine (T3) 193 -- 9.2.15 Trandolapril 193 -- 9.3 On-Line Simultaneous Assay of Enantiomers ...
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A dual-mode functional chip for chiral sensing based on mobile phone wettability measurements and portable surface-enhanced Raman spectroscopy (SERS) is reported. The plasmon-active regular gold grating surface was covalently grafted with chiral recognition moieties, l- or d-enantiomers of tartaric acid, making stereoselective discrimination of chiral amines possible. Chiral sensing of amines includes two modes of analysis, performed subsequently on the one chip surface with portable instruments (mobile phone equipped with a camera and developed application (app) Dropangle and a portable Raman spectrometer). First, the wettability changes, caused by enantioselective entrapping of chiral amines, are monitored and analyzed via our mobile phone app, allowing detection of the optical configuration and concentration of enantiomers with 1 order of magnitude accuracy. Second, SERS measurement on the same chip provides information about the chemical structure of entrapped amines and allows calculation of the enantiomeric excess with great accuracy. The applicability of the developed chip is demonstrated on a variety of chiral amines, including tyrosine, cysteine, dopamine (DOPA), and dextromethorphan in analytical solutions and in commercially available DOPA-containing drug. Moreover, we demonstrate that the chips could be regenerated and used repeatedly for at least five cycles.
The chiral recognition of organic compounds is of vital importance in the field of pharmacology and medicine. Unfortunately, the common analytical routes used in this field are significantly restricted by time spent and equipment demands. In this work, we propose an unprecedented alternative, aimed at enantiomer discrimination and estimation of their concentrations in an uncomplicated and instantaneous manner. The proposed approach is based on the creation of an optical fiber probe with two pronounced plasmonic bands attributed to gold and silver. The gold or silver surfaces were grafted with moieties, able to enunciating entrap chiral amines from solution, resulting in a wavelength shift corresponding to each plasmonic metal. As a model compound of chiral amine, we chose the DOPA, also taking in mind its high medical relevancy. For chiral detection, the optical fiber probe was simply immersed in an analytical solution of DOPA, and the selective shift of gold or silver plasmon bands was observed in the reflected light depending on DOPA chirality. The observed shifts depend on the concentration of DOPA enantiomers. In the case of a racemic mixture, the shifts of both plasmonic bands emerge, making possible the simultaneous determination of enantiomer concentrations and their ratio. The analytical cycle takes several minutes and requires very simple laboratory equipment.
