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1.  Origin of Homochirality in Biosystems 
Experimental data for a series of central and simple molecules in biosystems show that some amino acids and a simple sugar molecule have a chiral discrimination in favor of homochirality. Models for segregation of racemic mixtures of chiral amphiphiles and lipophiles in aqueous solutions show that the amphiphiles with an active isomerization kinetics can perform a spontaneous break of symmetry during the segregation and self-assembly to homochiral matter. Based on this observation it is argued that biomolecules with a sufficiently strong chiral discrimination could be the origin of homochirality in biological systems.
doi:10.3390/ijms10031290
PMCID: PMC2672030  PMID: 19399249
Origin of chirality; Origin of Life; Prebiotic self-assambly
2.  Chiral Polychlorinated Biphenyl Transport, Metabolism and Distribution - A Review 
Environmental science & technology  2010;44(8):2757-2766.
Chirality can be exploited to gain insight into enantioselective fate processes that may otherwise remain undetected because only biological, but not physical and chemical transport and transformation processes in an achiral environment will change enantiomer compositions. This review provides an in-depth overview of the application of chirality to the study of chiral polychlorinated biphenyls (PCBs), an important group of legacy pollutants. Like other chiral compounds, individual PCB enantiomers may interact enantioselectively (or enantiospecifically) with chiral macromolecules, such as cytochrome P-450 enzymes or ryanodine receptors, leading to differences in their toxicological effects and the enantioselective formation of chiral biotransformation products. Species and congener-specific enantiomer enrichment has been demonstrated in environmental compartments, wildlife and mammals, including humans, typically due to a complex combination of biotransformation processes and uptake via the diet by passive diffusion. Changes in the enantiomer composition of chiral PCBs in the environment have been used to understand complex aerobic and anaerobic microbial transformation pathways, to delineate and quantify PCB sources and transport in the environment, to gain insight into the biotransformation of PCBs in aquatic food webs, and to investigate the enantioselective disposition of PCBs and their methylsulfonyl PCBs metabolites in rodents. Overall, changes in chiral signatures are powerful, but currently underutilized tools for studies of environmental and biological processes of PCBs.
doi:10.1021/es902208u
PMCID: PMC2855137  PMID: 20384371
3.  The influence of terminal 3', 5' phosphates on conformations of dApdA. 
Nucleic Acids Research  1979;6(6):2165-2178.
Addition of 3' and 5' terminal phosphates to dApdA causes a decrease in conformational flexibility. pdApdAp has much fewer conformers with energies below 2.5 kcal./mole than dApdA. THE A, B and Watson-Crick (34) helices are the most preferred forms. Other important conformations are in the trans domain of psi. Thus, flexibility in psi as well as in omega and omega, and in the sugar pucker is indicated. The transformation from the B helix to the Watson-Crick helix follows a low energy path. This is significant since Watson-Crick conformations may be important for intercalation into nucleic acid polymers (40-42) above the dimer level. The B helix is preferred over the A form in these large DNA subunits.
PMCID: PMC327843  PMID: 461185
4.  Helical ambivalency induced by point mutations 
Background
Mutation of amino acid sequences in a protein may have diverse effects on its structure and function. Point mutations of even a single amino acid residue in the helices of the non-redundant database may lead to sequentially identical peptides which adopt different secondary structures in different proteins. However, various physico-chemical factors which govern the formation of these ambivalent helices generated by point mutations of a sequence are not clearly known.
Results
Sequences generated by point mutations of helices are mapped on to their non-helical counterparts in the SCOP database. The results show that short helices are prone to transform into non-helical conformations upon point mutations. Mutation of amino acid residues by helix breakers preferentially yield non-helical conformations, while mutation with residues of intermediate helix propensity display least preferences for non-helical conformations. Differences in the solvent accessibility of the mutating/mutated residues are found to be a major criteria for these sequences to conform to non-helical conformations. Even with minimal differences in the amino acid distributions of the sequences flanking the helical and non-helical conformations, helix-flanking sequences are found be more solvent accessible.
Conclusions
All types of mutations from helical to non-helical conformations are investigated. The primary factors attributing such changes in conformation can be: i) type/propensity of the mutating and mutant residues ii) solvent accessibility of the residue at the mutation site iii) context/environment dependence of the flanking sequences. The results from the present study may be used to design de novo proteins via point mutations.
doi:10.1186/1472-6807-13-9
PMCID: PMC3683331  PMID: 23675772
5.  Contrasting enantioselective DNA preference: chiral helical macrocyclic lanthanide complex binding to DNA 
Nucleic Acids Research  2012;40(16):8186-8196.
There is great interest in design and synthesis of small molecules which selectively target specific genes to inhibit biological functions in which particular DNA structures participate. Among these studies, chiral recognition has been received much attention because more evidences have shown that conversions of the chirality and diverse conformations of DNA are involved in a series of important life events. Here, we report that a pair of chiral helical macrocyclic lanthanide (III) complexes, (M)-Yb[LSSSSSS]3+ and (P)-Yb[LRRRRRR]3+, can enantioselectively bind to B-form DNA and show remarkably contrasting effects on GC-rich and AT-rich DNA. Neither of them can influence non-B-form DNA, nor quadruplex DNA stability. Our results clearly show that P-enantiomer stabilizes both poly(dG-dC)2 and poly(dA-dT)2 while M-enantiomer stabilizes poly(dA-dT)2, however, destabilizes poly(dG-dC)2. To our knowledge, this is the best example of chiral metal compounds with such contrasting preference on GC- and AT-DNA. Ligand selectively stabilizing or destabilizing DNA can interfere with protein–DNA interactions and potentially affect many crucial biological processes, such as DNA replication, transcription and repair. As such, bearing these unique capabilities, the chiral compounds reported here may shed light on the design of novel enantiomers targeting specific DNA with both sequence and conformation preference.
doi:10.1093/nar/gks524
PMCID: PMC3439914  PMID: 22675072
6.  The Origin of Biological Homochirality 
The single-handedness of biological molecules has fascinated scientists and laymen alike since Pasteur's first painstaking separation of the enantiomorphic crystals of a tartrate salt more than 150 yr ago. More recently, a number of theoretical and experimental investigations have helped to delineate models for how one enantiomer might have come to dominate over the other from what presumably was a racemic prebiotic world. This article highlights mechanisms for enantioenrichment that include either chemical or physical processes, or a combination of both. The scientific driving force for this work arises from an interest in understanding the origin of life, because the homochirality of biological molecules is a signature of life.
Chemical and/or physical enrichment processes led a prebiotic racemic mixture of molecules to generate living systems in which all sugars and amino acids are right- and left-handed, respectively.
doi:10.1101/cshperspect.a002147
PMCID: PMC2857173  PMID: 20452962
7.  Cyclodextrin Derivatives as Chiral Supramolecular Receptors for Enantioselective Sensing 
Sensors (Basel, Switzerland)  2006;6(6):593-615.
In view of the chiral nature of many bio-molecules (and all bio-macromolecules), most of therapeutically active compounds which target these molecules need to be chiral and “good handed” to be effective. In addition to asymmetric synthetic and separation methodologies, enantioselective chemical sensors, able to distinguish between two enantiomers of the same molecule, are of relevance. In order to design these sensing tools, two major classes of enantioselective layers have been developed. The first is based on molecularly imprinted polymers which are produced (polymerized) in the presence of their target, thus the polymeric material keep in “memory” the size and the shape of this molecule and the system could be used for sensing (not reviewed here). The second approach makes use of sensitive layers containing chiral macrocyclic receptors able of stereoselective molecular recognition; these receptors are mainly based on cyclodextrins. In this contribution, are reviewed achievements in the use of native or chemically modified cyclodextrins for chiral sensing purposes (at interfaces). Potentialities of other chiral macrocycles based on calixarenes, calix-resorcinarenes or crown-ethers as supramolecular receptors for enantioselective sensing are discussed.
PMCID: PMC3874827
Stereoselective Sensor; Macrocycle; Cyclodextrin; Calixarene; Crown-ether; Supramolecular Chemistry
8.  Hierarchical chirality transfer in the growth of Towel Gourd tendrils 
Scientific Reports  2013;3:3102.
Chirality plays a significant role in the physical properties and biological functions of many biological materials, e.g., climbing tendrils and twisted leaves, which exhibit chiral growth. However, the mechanisms underlying the chiral growth of biological materials remain unclear. In this paper, we investigate how the Towel Gourd tendrils achieve their chiral growth. Our experiments reveal that the tendrils have a hierarchy of chirality, which transfers from the lower levels to the higher. The change in the helical angle of cellulose fibrils at the subcellular level induces an intrinsic torsion of tendrils, leading to the formation of the helical morphology of tendril filaments. A chirality transfer model is presented to elucidate the chiral growth of tendrils. This present study may help understand various chiral phenomena observed in biological materials. It also suggests that chirality transfer can be utilized in the development of hierarchically chiral materials having unique properties.
doi:10.1038/srep03102
PMCID: PMC3813933  PMID: 24173107
9.  Raman and Raman optical activity (ROA) analysis of RNA structural motifs in Domain I of the EMCV IRES 
Nucleic Acids Research  2007;35(4):1169-1177.
Raman and Raman optical activity (ROA) spectra were collected for four RNA oligonucleotides based on the EMCV IRES Domain I to assess the contributions of helix, GNRA tetraloop, U·C mismatch base pair and pyrimidine-rich bulge structures to each. Both Raman and ROA spectra show overall similarities for all oligonucleotides, reflecting the presence of the same base paired helical regions and GNRA tetraloop in each. Specific bands are sensitive to the effect of the mismatch and asymmetric bulge on the structure of the RNA. Raman band changes are observed that reflect the structural contexts of adenine residues, disruption of A-form helical structure, and incorporation of pyrimidine bases in non-helical regions. The ROA spectra are also sensitive to conformational mobility of ribose sugars, and verify a decrease in A-type helix content upon introduction of the pyrimidine-rich bulge. Several Raman and ROA bands also clearly show cooperative effects between the mismatch and pyrimidine-rich bulge motifs on the structure of the RNA. The complementary nature of Raman and ROA spectra provides detailed and highly sensitive information about the local environments of bases, and secondary and tertiary structures, and has the potential to yield spectral signatures for a wide range of RNA structural motifs.
doi:10.1093/nar/gkm012
PMCID: PMC1851652  PMID: 17264119
10.  SURVEY AND SUMMARY: Difference in conformational diversity between nucleic acids with a six-membered ‘sugar’ unit and natural ‘furanose’ nucleic acids 
Nucleic Acids Research  2003;31(12):2975-2989.
Natural nucleic acids duplexes formed by Watson–Crick base pairing fold into right-handed helices that are classified in two families of secondary structures, i.e. the A- and B-form. For a long time, these A and B allomorphic nucleic acids have been considered as the ‘non plus ultra’ of double-stranded nucleic acids geometries with the only exception of Z-DNA, a left-handed helix that can be adopted by some DNA sequences. The five-membered furanose ring in the sugar–phosphate backbone of DNA and RNA is the underlying cause of this restriction in conformational diversity. A collection of new Watson–Crick duplexes have joined the ‘original’ nucleic acid double helixes at the moment the furanose sugar was replaced by different types of six-membered ring systems. The increase in this structural and conformational diversity originates from the rigid chair conformation of a saturated six-membered ring that determines the orientation of the ring substituents with respect to each other. The original A- and B-form oligonucleotide duplexes have expanded into a whole family of new structures with the potential for selective cross-communication in a parallel or antiparallel orientation, opening up a new world for information storage and for molecular recognition-directed self-organization.
PMCID: PMC162241  PMID: 12799423
11.  Gas Phase Chiral Separations By Ion Mobility Spectrometry 
Analytical chemistry  2006;78(24):8200-8206.
This manuscript introduces the concept of Chiral Ion Mobility Spectrometry (CIMS) and presents examples demonstrating the gas phase separation of enantiomers of a wide range of racemates including pharmaceuticals, amino acids and carbohydrates. CIMS is similar to traditional ion mobility spectrometry (IMS), where gas phase ions, when subjected to a potential gradient are separated at atmospheric pressure due to differences in their shapes and sizes. In addition to size and shape, CIMS separates ions based on their stereospecific interaction with a chiral gas. In order to achieve chiral discrimination by CIMS, an asymmetric environment was provided by doping the drift gas with a volatile chiral reagent. In this study S-(+)-2-butanol was used as a chiral modifier to demonstrate enantiomeric separations of atenolol, serine, methionine, threonine, methyl-α-glucopyranoside, glucose, penicillamine, valinol, phenylalanine, and tryptophan from their respective racemic mixtures.
doi:10.1021/ac0608772
PMCID: PMC3633475  PMID: 17165808
12.  Integrated Molecular Chirality, Absolute Helicity, and Intrinsic Chiral Topology in Three-Dimensional Open-Framework Materials 
Journal of the American Chemical Society  2008;130(51):17246-17247.
While chiral materials are common, few are known that integrate molecular chirality, absolute helicity, and 3-D intrinsically chiral topological nets in one material. Such multi-homochiral features may lead to enhanced chiral recognition processes that are important for enantioselective catalysis or separation. Reported here are a series of 3-D open-framework materials with unusual integration of various homochiral and homohelical features, even in the bulk sample.
doi:10.1021/ja8075692
PMCID: PMC2782683  PMID: 19053443
13.  Chirality Emergence in Thin Solid Films of Amino Acids by Polarized Light from Synchrotron Radiation and Free Electron Laser 
One of the most attractive hypothesis for the origin of homochirality in terrestrial bioorganic compounds is that a kind of “chiral impulse” as an asymmetric excitation source induced asymmetric reactions on the surfaces of such materials such as meteorites or interstellar dusts prior to the existence of terrestrial life (Cosmic Scenario). To experimentally introduce chiral structure into racemic films of amino acids (alanine, phenylalanine, isovaline, etc.), we irradiated them with linearly polarized light (LPL) from synchrotron radiation and circularly polarized light (CPL) from a free electron laser. After the irradiation, we evaluated optical anisotropy by measuring the circular dichroism (CD) spectra and verified that new Cotton peaks appeared at almost the same peak position as those of the corresponding non-racemic amino acid films. With LPL irradiation, two-dimensional anisotropic structure expressed as linear dichroism and/or linear birefringence was introduced into the racemic films. With CPL irradiation, the signs of the Cotton peaks exhibit symmetrical structure corresponding to the direction of CPL rotation. This indicates that some kinds of chiral structure were introduced into the racemic film. The CD spectra after CPL irradiation suggest the chiral structure should be derived from not only preferential photolysis but also from photolysis-induced molecular structural change. These results suggest that circularly polarized light sources in space could be associated with the origin of terrestrial homochirality; that is, they would be effective asymmetric exciting sources introducing chiral structures into bio-organic molecules or complex organic compounds.
doi:10.3390/ijms10073044
PMCID: PMC2738911  PMID: 19742124
chirality; circularly polarized light; amino acids; solid films; synchrotron radiation; free electron laser; origin of terrestrial homochirality
14.  Electrostatic free energy landscapes for nucleic acid helix assembly 
Nucleic Acids Research  2006;34(22):6629-6639.
Metal ions are crucial for nucleic acid folding. From the free energy landscapes, we investigate the detailed mechanism for ion-induced collapse for a paradigm system: loop-tethered short DNA helices. We find that Na+ and Mg2+ play distinctive roles in helix–helix assembly. High [Na+] (>0.3 M) causes a reduced helix–helix electrostatic repulsion and a subsequent disordered packing of helices. In contrast, Mg2+ of concentration >1 mM is predicted to induce helix–helix attraction and results in a more compact and ordered helix–helix packing. Mg2+ is much more efficient in causing nucleic acid compaction. In addition, the free energy landscape shows that the tethering loops between the helices also play a significant role. A flexible loop, such as a neutral loop or a polynucleotide loop in high salt concentration, enhances the close approach of the helices in order to gain the loop entropy. On the other hand, a rigid loop, such as a polynucleotide loop in low salt concentration, tends to de-compact the helices. Therefore, a polynucleotide loop significantly enhances the sharpness of the ion-induced compaction transition. Moreover, we find that a larger number of helices in the system or a smaller radius of the divalent ions can cause a more abrupt compaction transition and a more compact state at high ion concentration, and the ion size effect becomes more pronounced as the number of helices is increased.
doi:10.1093/nar/gkl810
PMCID: PMC1751542  PMID: 17145719
15.  Mechanism of chiral proofreading during translation of the genetic code 
eLife  2013;2:e01519.
The biological macromolecular world is homochiral and effective enforcement and perpetuation of this homochirality is essential for cell survival. In this study, we present the mechanistic basis of a configuration-specific enzyme that selectively removes D-amino acids erroneously coupled to tRNAs. The crystal structure of dimeric D-aminoacyl-tRNA deacylase (DTD) from Plasmodium falciparum in complex with a substrate-mimicking analog shows how it uses an invariant ‘cross-subunit’ Gly-cisPro dipeptide to capture the chiral centre of incoming D-aminoacyl-tRNA. While no protein residues are directly involved in catalysis, the unique side chain-independent mode of substrate recognition provides a clear explanation for DTD’s ability to act on multiple D-amino acids. The strict chiral specificity elegantly explains how the enriched cellular pool of L-aminoacyl-tRNAs escapes this proofreading step. The study thus provides insights into a fundamental enantioselection process and elucidates a chiral enforcement mechanism with a crucial role in preventing D-amino acid infiltration during the evolution of translational apparatus.
DOI: http://dx.doi.org/10.7554/eLife.01519.001
eLife digest
Amino acids are ‘chiral’ molecules that come in two different forms, called D and L, which are mirror images of each other, similar to how our left and right hands are mirror images of each other. However, only one of these forms is used to make proteins: the more abundant L-amino acids are linked together to make proteins, whereas the scarcer D-amino acids are not. This ‘homochirality’ is common to all life on Earth.
The molecular machinery inside cells that manufactures proteins involves many enzymes that carry out different tasks. Among these is an enzyme called DTD (short for D-aminoacyl-tRNA deacylase), which prevents D-amino acids being incorporated into proteins. To do this, DTD must be able to recognise and remove the D forms of many different amino acids before they are taken to the growing protein by transfer RNA molecules. However, the details of this process are not fully understood.
To investigate this mechanism, Ahmad et al. made crystals of the DTD enzyme in complex with a molecule that mimics a D-amino acid attached to a transfer RNA molecule. By studying this structure at a high resolution, Ahmad et al. were able to identify how the active site of DTD can specifically accommodate the ‘chiral centre’ of a complex made of a D-amino acid and a transfer RNA molecule.
DTD is able to recognize D-amino acids because of a critical dipeptide that is inserted from one subunit of the DTD into the active site of another subunit of the enzyme. The effect of this dipeptide is to generate a binding pocket that is a perfect fit for the chiral centre of a complex that contains a D-amino acid and a transfer RNA molecule. Moreover, this pocket specifically excludes complexes that contain an L-amino acid.
The crucial parts of DTD that form the binding pocket are highly conserved—that is, they are the same in a wide variety of organisms, from bacteria to mammals. This conservation suggests that DTD is crucial for ensuring homochirality throughout all forms of life. Intriguingly, DTD is particularly highly expressed in neurons which are abundant in D-amino acids: this indicates that the DTD enzyme has an important physiological role, which will certainly be the focus of future work.
DOI: http://dx.doi.org/10.7554/eLife.01519.002
doi:10.7554/eLife.01519
PMCID: PMC3845328  PMID: 24302572
homochirality; proofreading; enzyme mechanism; translation; E. coli; Plasmodium falciparum
16.  Chirality and anaesthetic drugs: A review and an update 
Indian Journal of Anaesthesia  2011;55(6):556-562.
Many molecules can exist as right-handed and left-handed forms that are non-superimposable mirror images of each other. They are known as enantiomers or substances of opposite shape. Such compounds are also said to be chiral (Greek chiros meaning ‘hand’). Such chiral molecules are of great relevance to anaesthetic theory and practice. This review summarizes the basic concepts, pharmacokinetic and pharmacodynamic aspects of chirality, and some specific examples of their application in anaesthesia, along with recent advances to elucidate the anaesthetic mechanisms. Chirality is relevant to anaesthesia, simply because more than half of the synthetic agents used in anaesthesia practice are chiral drugs. Almost all these synthetic chiral drugs are administered as racemic mixture, rather than as single pure enantiomers. These mixtures are not drug formulations containing two or more therapeutic substances, but combination of isomeric substances, with the therapeutic activity residing mainly in one of the enantiomer. The other enantiomer can have undesirable properties, have different therapeutic activities or be pharmacologically inert. Specific examples of application of chirality in anaesthetic drugs include inhalational general anaesthetics (e.g. isoflurane), intravenous anaesthetics (e.g. etomidate, thiopentone), neuromuscular blocking agents (e.g. cisatracurium), local anaesthetics (e.g. ropivacaine and levobupivacaine) and other agents (e.g. levosimendan, dexmedetomidine, L-cysteine). In the recent advances, chirality study has not only helped new drug development as mentioned above, but has also contributed in a more profound way to the understanding of the mechanism of anaesthesia and anaesthetic drugs.
doi:10.4103/0019-5049.90608
PMCID: PMC3249860  PMID: 22223897
Anaesthesia; anaesthetic drugs; chirality; enantiomers
17.  Nanoconfinement-Induced Structures in Chiral Liquid Crystals 
We employ Monte Carlo simulations in a specialized isothermal-isobaric and in the grand canonical ensemble to study structure formation in chiral liquid crystals as a function of molecular chirality. Our model potential consists of a simple Lennard-Jones potential, where the attractive contribution has been modified to represent the orientation dependence of the interaction between a pair of chiral liquid-crystal molecules. The liquid crystal is confined between a pair of planar and atomically smooth substrates onto which molecules are anchored in a hybrid fashion. Hybrid anchoring allows for the formation of helical structures in the direction perpendicular to the substrate plane without exposing the helix to spurious strains. At low chirality, we observe a cholesteric phase, which is transformed into a blue phase at higher chirality. More specifically, by studying the unit cell and the spatial arrangement of disclination lines, this blue phase can be established as blue phase II. If the distance between the confining substrates and molecular chirality are chosen properly, we see a third structure, which may be thought of as a hybrid, exhibiting mixed features of a cholesteric and a blue phase.
doi:10.3390/ijms140917584
PMCID: PMC3794743  PMID: 23989605
liquid crystal; chirality; cholesteric and blue phases; confinement; Monte Carlo simulation
18.  Conformational Behavior of Chemically Reactive Alanine-Rich Repetitive Protein Polymers 
Biomacromolecules  2005;6(3):1531-1539.
The synthesis of protein-based polymers with controlled conformational properties and functional group placement offers many opportunities for the design of advanced materials. In this work, protein engineering methods have been used to produce repetitive alanine-rich protein polymers with the sequence [(AAAQ)5-(AAAE)(AAAQ)5]x (x = 2 and 6); these macromolecules may mimic architectural features of certain alanine-rich helical sequences found in natural proteins. Various proteins from this family can be readily expressed and purified from Escherichia coli. Circular dichroic spectroscopy (CD) characterization demonstrates that the purified proteins are highly helical under a variety of conditions. Thermal analysis of [(AAAQ)5(AAAE)-(AAAQ)5]2 via differential scanning calorimetry (DSC) and CD indicates that the protein undergoes a reversible helix–coil transition at approximately 45 °C and that the protein conformation can be manipulated at elevated temperatures depending on solution conditions. The demonstrated conformational properties of these artificial proteins suggest that they may be excellent candidates for elucidating structure–function relationships in biopolymers for nanotechnology and biological applications.
doi:10.1021/bm049216+
PMCID: PMC2650394  PMID: 15877375
19.  G-Quadruplex binding enantiomers show chiral selective interactions with human telomere 
Nucleic Acids Research  2014;42(6):3792-3802.
Chiral recognition of DNA molecules is important because DNA chiral transition and its different conformations are involved in a series of important life events. Among them, polymorphic human telomere DNA has attracted great interests in recent years because of its important roles in chromosome structural integrity. In this report, we examine the short-term effect of chiral metallo-supramolecular complex enantiomers treatment on tumor cells, and find that a zinc-finger-like alpha helical chiral metallo-supramolecular complex, [Ni2L3]4+-P enantiomer (NiP), can selectively provoke the rapid telomere uncapping, trigger DNA damage responses at telomere and degradation of G-overhang and the delocalization of telomeric protein from telomeres. Further studies indicate that NiP can induce an acute cellular apoptosis and senescence in cancer cells rather than normal cells. These results are further evidenced by the upregulation of p21 and p16 proteins. Moreover, NiP can cause translocation of hTERT from nuclear to cytoplasm through Tyr 707 phosphorylation. While its enantiomer, [Ni2L3]4+-M (NiM), has no such mentioned effects, these results clearly demonstrate the compound’s chiral selectivity in cancer cells. Our work will shed light on design of chiral anticancer drugs targeting G-quadruplex DNA, and developing telomere and telomerase modulation agents.
doi:10.1093/nar/gkt1354
PMCID: PMC3973297  PMID: 24413564
20.  Probing DNA Bulges with Designed Helical Spirocyclic Molecules 
Biochemistry  2007;46(2):561-567.
Since bulged structures (unpaired bases) in nucleic acids are of general biological significance, it has been of interest to design small molecules as specific probes of bulge function. Based on our earlier work with the specific DNA bulge-binding metabolite obtained from the enediyne antitumor antibiotic neocarzinostatin chromophore (NCS-chrom) we have prepared three small helical spirocyclic molecules that most closely mimic the natural product. These wedge-shaped molecules resemble the natural product in having the sugar residue attached to the same 5-membered ring system. In one instance the sugar is aminoglucose in β-glycosidic linkage and in the other, two enantiomers having the natural sugar N-methylfucosamine in α-glycosidic linkage. All three analogues were found to interfere with bulge-specific cleavage by NCS-chrom and with the ability of bulged-DNA to serve as a template for DNA polymerase 1 in accord with their binding affinities for DNA containing a 2-base bulge. Comparable results were obtained with the analogues for the less efficiently cleaved 3-base bulge DNA structures. In each situation the enantiomers possessing the natural sugar in α-glycosidic linkage are the most potent inhibitors of the cleavage reaction. In the DNA polymerase reactions again the closest natural product mimics were the most effective in selectively impeding nucleotide extension at the bulge site, presumably by complex formation. These results demonstrate the potential usefulness of bulge-binding compounds in modifying DNA structure and function and support efforts to design and prepare reactive species of these molecules that can covalently modify bulged DNA.
doi:10.1021/bi061744d
PMCID: PMC2569198  PMID: 17209566
21.  Surface chirality induced by rotational electrodeposition in magnetic fields 
Scientific Reports  2013;3:2574.
The surfaces of minerals could serve important catalytic roles in the prebiotic syntheses of organic molecules, such as amino acids. Thus, the surface chirality is responsible for the asymmetric syntheses of biomolecules. Here, we show induction of the surface chirality of copper metal film by electrodeposition via electrochemical cell rotation in magnetic fields. Such copper film electrodes exhibit chiral behaviour in the electrochemical reaction of alanine enantiomers, and the rotating direction allows control of the chiral sign. These findings are discussed in connection with the asymmetric influence of the system rotation on the magnetohydrodynamic micro-vortices around the electrode surfaces.
doi:10.1038/srep02574
PMCID: PMC3759836  PMID: 23999254
22.  Chiral separation of α-cyclohexylmandelic acid enantiomers by high-speed counter-current chromatography with biphasic recognition 
Journal of chromatography. A  2010;1217(18):3044-3052.
This work concentrates on a novel chiral separation technology named biphasic recognition applied to resolution of α-cyclohexylmandelic acid enantiomers by high-speed counter-current chromatography (HSCCC). The biphasic chiral recognition HSCCC was performed by adding lipophilic (−)-2-ethylhexyl tartrate in the organic stationary phase and hydrophilic hydroxypropyl-β-cyclodextrin in the aqueous mobile phase, which preferentially recognized the (−)-enantiomer and (+)-enantiomer, respectively. The two-phase solvent system composed of n-hexane-methyl tert-butyl ether-water (9:1:10, v/v/v) with the above chiral selectors was selected according to the partition coefficient and separation factor of the target enantiomers. Various parameters involved in the chiral separation were investigated, namely the types of the chiral selector (CS); the concentration of each chiral selector; pH of the mobile phase; and the separation temperature. The mechanism involved in this biphasic recognition chiral separation by HSCCC was discussed. Langmuirian isotherm was employed to estimate the loading limits for each chiral selector. The overall experimental results show that the HSCCC separation of enantiomer based on biphasic recognition is much more efficient than the traditional monophasic recognition chiral separation, since it utilizes the cooperation of both lipophilic and hydrophilic chiral selectors.
doi:10.1016/j.chroma.2010.02.077
PMCID: PMC2854300  PMID: 20303497
Chiral separation; High-speed counter-current chromatography; Biphasic chiral recognition; α-Cyclohexylmandelic acid; Optical activity
23.  A screening method for chiral selectors that does not require covalent attachment 
A high throughput screening protocol is proposed for chiral selector discovery. It is modeled after the protocol for biological screening of candidate drugs from chemical libraries. The procecure works based on target distribution between an aqueous phase and an organic phase. The target may be a racemate or separate enantiomers. Screening for noncovalent intermolecular association between target and candidate selectors is carried out by partitioning experiments in the presence and absence of the candidate chiral selectors in the organic phase (plasticized poly(vinylchloride)).The partition ratio measurement uses 96-well plates for high throughput. The feasibility of this approach is validated by working with a known target/chiral selector pair, N-(3,5-dinitrobenzoyl)-α-phenylglycine and 2,2,2-trifluoro-1-(9-anthryl)ethanol. The validated protocol is applied to a small library of 12 cyclopropyl dipeptide isosteres. Eight bind the racemic target, econazole. Among them, one has measurable chiral selectivity. The advantage of the method is that it does not require the covalent attachment of either the analyte or the selector, and the required amount of the potential chiral selector is about 100 micrograms.
doi:10.1021/ja058004x
PMCID: PMC2536637  PMID: 16478163
24.  Chiral plasmonics of self-assembled nanorod dimers 
Scientific Reports  2013;3:1934.
Chiral nanoscale photonic systems typically follow either tetrahedral or helical geometries that require four or more different constituent nanoparticles. Smaller number of particles and different chiral geometries taking advantage of the self-organization capabilities of nanomaterials will advance understanding of chiral plasmonic effects, facilitate development of their theory, and stimulate practical applications of chiroplasmonics. Here we show that gold nanorods self-assemble into side-by-side orientated pairs and “ladders” in which chiral properties originate from the small dihedral angle between them. Spontaneous twisting of one nanorod versus the other one breaks the centrosymmetric nature of the parallel assemblies. Two possible enantiomeric conformations with positive and negative dihedral angles were obtained with different assembly triggers. The chiral nature of the angled nanorod pairs was confirmed by 4π full space simulations and the first example of single-particle CD spectroscopy. Self-assembled nanorod pairs and “ladders” enable the development of chiral metamaterials, (bio)sensors, and new catalytic processes.
doi:10.1038/srep01934
PMCID: PMC3678134  PMID: 23752317
25.  Spontaneous chiral symmetry breaking in early molecular networks 
Biology Direct  2010;5:38.
Background
An important facet of early biological evolution is the selection of chiral enantiomers for molecules such as amino acids and sugars. The origin of this symmetry breaking is a long-standing question in molecular evolution. Previous models addressing this question include particular kinetic properties such as autocatalysis or negative cross catalysis.
Results
We propose here a more general kinetic formalism for early enantioselection, based on our previously described Graded Autocatalysis Replication Domain (GARD) model for prebiotic evolution in molecular assemblies. This model is adapted here to the case of chiral molecules by applying symmetry constraints to mutual molecular recognition within the assembly. The ensuing dynamics shows spontaneous chiral symmetry breaking, with transitions towards stationary compositional states (composomes) enriched with one of the two enantiomers for some of the constituent molecule types. Furthermore, one or the other of the two antipodal compositional states of the assembly also shows time-dependent selection.
Conclusion
It follows that chiral selection may be an emergent consequence of early catalytic molecular networks rather than a prerequisite for the initiation of primeval life processes. Elaborations of this model could help explain the prevalent chiral homogeneity in present-day living cells.
Reviewers
This article was reviewed by Boris Rubinstein (nominated by Arcady Mushegian), Arcady Mushegian, Meir Lahav (nominated by Yitzhak Pilpel) and Sergei Maslov.
doi:10.1186/1745-6150-5-38
PMCID: PMC2894767  PMID: 20507625

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