Pairing Affinity Research Articles

ChemInform Abstract: Synthesis of Indole Derivatives from 2‐Alkynylanilines by Means of Gold Catalysis

AbstractReview: [64 refs.

Dynamical simulation of electrostatic striped colloidal particles.

The static and dynamic properties of striped colloidal particles are obtained using molecular dynamics computer simulations. Striped particles with n = 2 to n = 7 stripes of alternating electric charge are modeled at a high level of detail through a pointwise (PW) representation of the particle surface. We also consider the extent to which striped particles are similar to comparable isotropically attractive particles-such as depletion attracting colloids-by modeling striped particles with an isotropic pair interaction computed by coarse-graining (CG) over orientations at a pair level. Surprisingly, the CG models reproduce the static structure of the PW models for a range of volume fractions and interaction strengths consistent with the fluid region of the phase diagram for all n. As a corollary, different n-striped particle systems with comparable pair affinities (e.g., dimer equilibrium constant) have similar static structure. Stronger pair interactions lead to a collapsed structure in simulation as consistent with a glass-like phase. Different n-striped particle systems are found to have different phase boundaries and for certain n's no glass-like state is observed in any of our simulations. The CG model is found to have accelerated dynamics relative to the PW model for the same range of fluid conditions for which the models have identical static structure. This suggests striped electrostatic particles have slower dynamics than comparable isotropically attractive colloids. The slower dynamics result from a larger number of long-duration reversible bonds between pairs of striped particles than seen in isotropically attractive systems. We also found that higher n-striped particles systems generally have slower dynamics than lower n-striped systems with comparable pair affinities.

Computational Approaches to Predicting the Impact of Novel Bases on RNA Structure and Stability

The use of computational modeling techniques to gain insight into nucleobase interactions has been a challenging endeavor to date. Accurate treatment requires the tackling of many challenges but also holds the promise of great rewards. The development of effective computational approaches to predict the binding affinities of nucleobases and analogues can, for example, streamline the process of developing novel nucleobase modifications, which should facilitate the development of new RNAi-based therapeutics. This brief review focuses on available computational approaches to predicting base pairing affinity in RNA-based contexts such as nucleobase-nucleobase interactions in duplexes and nucleobase-protein interactions. The challenges associated with such modeling along with potential future directions for the field are highlighted.

The role of Cr and Si in affecting high-temperature oxidation behaviour of minor Dy doped NiAl alloys

Isothermal and cyclic oxidation behaviour of Cr/Si co-doped NiAlDy alloys were investigated at 1200°C. The role of Cr and Si in oxidation of NiAlDy alloys was discussed by combining experimental results and first-principles calculations. Cr and Si would co-segregate at grain boundaries and promoted the transformation from θ-Al2O3 to α-Al2O3 at initial oxidation stage. The NiAlDyCr–3Si alloy yielded a mass gain of ∼0.64mg/cm2 after 100h isothermal oxidation and showed much improved cyclic oxidation resistance due to the pair affinity between Si and Cr which can alleviate the deleterious effect of interfacial Cr precipitation.

Synthesis of Indole Derivatives from 2‐Alkynylanilines by Means of Gold Catalysis

AbstractThe peculiar features of gold(III) and gold(I) species include exceptional carbophilicity and, at the same time, lone pair affinity. Such a combination offers many advantages for the development of more sustainable approaches to the synthesis of indole derivatives from readily available 2‐alkynylanilines. This mini‐review critically summarizes the literature reports in this field, with the aim to encourage further research activities in this promising area.

Genome-Scale Screening of Drug-Target Associations Relevant to Ki Using a Chemogenomics Approach

The identification of interactions between drugs and target proteins plays a key role in genomic drug discovery. In the present study, the quantitative binding affinities of drug-target pairs are differentiated as a measurement to define whether a drug interacts with a protein or not, and then a chemogenomics framework using an unbiased set of general integrated features and random forest (RF) is employed to construct a predictive model which can accurately classify drug-target pairs. The predictability of the model is further investigated and validated by several independent validation sets. The built model is used to predict drug-target associations, some of which were confirmed by comparing experimental data from public biological resources. A drug-target interaction network with high confidence drug-target pairs was also reconstructed. This network provides further insight for the action of drugs and targets. Finally, a web-based server called PreDPI-Ki was developed to predict drug-target interactions for drug discovery. In addition to providing a high-confidence list of drug-target associations for subsequent experimental investigation guidance, these results also contribute to the understanding of drug-target interactions. We can also see that quantitative information of drug-target associations could greatly promote the development of more accurate models. The PreDPI-Ki server is freely available via: http://sdd.whu.edu.cn/dpiki.

CHEMOTAXONOMIC STUDY OF FIVE MONOCOT SPECIES FROM NORTH- EASTERN SUDAN

Alkaloids, flavonoids, triterpenes, sterols and saponins were qualitatively screened in different organs of five monocotyledonous species belonging to different genera: Allium cepaL., Asparagus densiflorus (Kunth) Jessop, Pancratium tortuosum Herbert., Kniphofia nubigena Mildr., and Urginea maritima (L.) Baker. Phenolic compounds were separated using thin layer chromatography to ascertain their relative phylogenetic position. Data collected from the qualitative phytochemical analysis, paired affinity, group affinity and isolation value reflected taxonomically significant information supported the inclusion of these species in different families by many taxonomists in the most recent classification systems.

Biochemical and Biophysical Properties of Interactions between Subunits of the Peripheral Stalk Region of Human V-ATPase

Peripheral stalk subunits of eukaryotic or mammalian vacuolar ATPases (V-ATPases) play key roles in regulating its assembly and disassembly. In a previous study, we purified several subunits and their isoforms of the peripheral stalk region of Homo sapiens (human) V-ATPase; such as C1, E1G1, H, and the N-terminal cytoplasmic region of Vo, a1. Here, we investigated the in vitro binding interactions of the subunits at the stalk region and measured their specific affinities. Surface plasmon resonance experiments revealed that the subunit C1 binds the E1G1 heterodimer with both high and low affinities (2.8 nM and 1.9 µM, respectively). In addition, an E1G1-H complex can be formed with high affinity (48 nM), whereas affinities of other subunit pairs appeared to be low (∼0.21−3.0 µM). The putative ternary complex of C1-H-E1G1 was not much strong on co-incubation of these subunits, indicating that the two strong complexes of C1-E1G1 and H-E1G1 in cooperation with many other weak interactions may be sufficiently strong enough to withstand the torque of rotation during catalysis. We observed a partially stable quaternary complex (consisting of E1G1, C1, a1NT, and H subunits) resulting from discrete peripheral subunit interactions stabilizing the complex through their intrinsic affinities. No binding was observed in the absence of E1G1 (using only H, C1, and a1NT); therefore, it is likely that, in vivo, the E1G1 heterodimer has a significant role in the initiation of subunit assembly. Multiple interactions of variable affinity in the stalk region may be important to the mechanism of reversible dissociation of the intact V-ATPase.

Elaboration of Immunoenzymatic Test-Kit for Total Human ΙgΕ Assay and Investigation of Its Analytical Properties

Enzyme-linked immunosorbent assay (ELISA) test-kit has been developed based on complex immuno-chemical, including epitop mapping, characteristics of monoclonal antibodies (MAbs) to human IgЕ. “Sandwich” type ELISA based on usage of different epitop directionality MAbs. It has been founded correlation between affinity of different MAb pairs and its sorbtion-detection ability. Optimal configuration of MAbs in “sandwich” ELISA was follow-ing: 164H10 - 165C12 and 164H10 - 166B7. Cooperative usage of horseradish peroxidase conjugates of MAbs directed to different epitops (165C12-HRP + 166B7-HRP) increased analytical sensitivity of assay and constituted 4.5 IU/ml. Analytical characteristics of developed test-kit were following: dynamic range – from 4.5 to 1600 IU/ml, variation coefficient value during one procedure – 4.2±2.1%, and between procedures – 4.8±2.3%. Presences of human IgG, IgA, IgМ, albumin (1 μg/ml) were not effect on the assay specificity (test concentration of IgE – 50 IU/ml).

ФЛАВОНОИДЫ НЕКОТОРЫХ ВИДОВ РОДА RHODODENDRON L. ФЛОРЫ СИБИРИ И ДАЛЬНЕГО ВОСТОКА

The composition and content of flavonoids glycosides and aglycones in the leaves of Rhododendron adamsii, Rh. parvifolium, Rh. impeditum, and the closely related species of the subsection Rhodorastra (Rh. dauricum, Rh. ledebourii, Rh. sichotense, Rh. mucronulatum) from populations of the Altai, Yakutia, Tuva, the Amur region and Primorsky Krai, Buryatia, China were studied by HPLC. The aglycones content in hydrolysates of the majority of the species is about 1%, and quercetin and dihydroquercetin prevail in aglycones composition. In Rh. adamsii and Rh. parvifolium aglycones are found predominantly in the free state, and in the species of the subsection Rhodorastra – in a bound one. Values of paired affinity of the investigated species on composition of phenolic compounds of extracts and hydrolysates vary from 30 to 90%, maximums are in pairs Rh. sichotense-Rh. dauricum, Rh. adamsii-Rh. ledebourii. As a result of the analysis of affinity of flavonoids composition of the species relation with D. Chamberlain’s anatomo-morphological classification is not exposed. Significant value of affinity Rh. adamsii and Rh. parvifolium is revealed. The minimum value of group affinity on flavonoids composition of extracts and hydrolysates of Rh. impeditum casts doubt on his position equally with Rh. parvifolium in the subsection Lapponica.

Modeling Cluster Formation by Multivalent Interacting Proteins: Nephrin-Nck-NWasp Signaling in the Foot Process of Kidney Podocytes

Intracellular function is often defined by clusters consisting of multiple multivalent molecules. Studying these clusters represents a significant challenge because of the potentially infinite number of cluster compositions and the intermediate complexes that are formed while clusters are formed. To make the matter worse, many clusters are very liquid, the affinities of the many bimolecular site interactions are quite modest, implying that off-rates are relatively rapid. Thus, we need efficient methods to predict the average composition of these ensembles, characterizing number of molecules of different types, number of bonds per different molecule types, and other parameters defining the size and structure of the cluster. Here we present a stochastic steady state algorithm for multivalent interacting molecules to determine cluster compositions and sizes based on probability that each type of binding site is bound. The advantage of the method is in its efficiency: tracking the formation of the cluster over time would require computation of binding and unbinding steps; instead, we identify a distribution of cluster compositions at the time point of interest based on the pairwise binding probability among multiple sites within interacting molecules. The method is applied to the system Nephrin-Nck-NWasp. The interaction between these three multi-domain molecules is required for maintenance of the podocyte foot processes cytoskeleton, the key cellular structure in the kidney slit diaphragm filtration system. The weak individual site pair affinities and estimated nephrin concentrations at the slit diaphragm by themselves would be insufficient to promote actin polymerization. We use our method to address how the multi domain and cooperative mechanisms could provide such function. Supported by NIH grants TR01DK087650 and P41GM103313.

Cytogenetic evidence of mixed disomic and polysomic inheritance in an allotetraploid (AABB) Musa genotype

Edible bananas originated mainly from two wild species, Musa acuminata Colla (AA) and Musa balbisiana Colla (BB), and triploid cultivars with an AAA, AAB or ABB genome are the most widely used. In the present study, chromosome pairing affinities are investigated in a sterile AB Indian variety and in its fertile colchicine-induced allotetraploid (AABB) derivative to determine the inheritance pattern of the tetraploid genotype. The potential implications of interspecific recombination and chromosomal composition of diploid gametes for Musa improvement are presented. The pairing of different chromosome sets at diploid and tetraploid levels was investigated through a combination of conventional cytogenetic and genomic in-situ hybridization (GISH) analyses of meiotic chromosomes, leading to a likelihood model of the pairing behaviour. GISH analysis of mitotic chromosomes was also conducted to reveal the chromosome constitution of hybrids derived from crosses involving the allotetraploid genotype. Analysis of chromosome associations at both ploidy levels suggested that the newly formed allotetraploid behaves as a 'segmental allotetraploid' with three chromosome sets in a tetrasomic pattern, three sets in a likely disomic pattern and the five remaining sets in an intermediate pattern. Balanced and unbalanced diploid gametes were detected in progenies, with the chromosome constitution appearing to be more homogenous in pollen than in ovules. Colchicine-induced allotetraploids in Musa provide access to the genetic background of natural AB varieties. The segmental inheritance pattern exhibited by the AABB allotetraploid genotype implies chromosome exchanges between M. acuminata and M. balbisiana species and opens new horizons for reciprocal transfer of valuable alleles.

Heterodimers Reveal That Two Arabinose Molecules Are Required for the Normal Arabinose Response of AraC

AraC protein, which regulates expression of the l-arabinose operon in Escherichia coli, is a dimer whose DNA binding affinity for pairs of DNA half-sites is controlled by arabinose. Here we have addressed the question of whether the arabinose response of AraC requires the binding of one or two molecules of arabinose. This was accomplished by measuring the DNA dissociation rates of wild-type AraC and heterodimeric AraC constructs in which one subunit is capable of binding arabinose and the other subunit does not bind arabinose. Solutions consisting entirely of heterodimers were formed by spontaneous subunit exchange between two different homodimers, with heterodimers being trapped by the formation of an intersubunit disulfide bond between cysteine residues strategically positioned within the dimerization interface. We found that the normal arabinose response of AraC requires the binding of two arabinose molecules. These results provide additional constraints on mechanistic models for the action of AraC.

Chromosome pairing affinities in interspecific hybrids reflect phylogenetic distances among lady's slipper orchids (Paphiopedilum)

Background and AimsLady's slipper orchids (Paphiopedilum) are of high value in floriculture, and interspecific hybridization has long been used for breeding improved cultivars; however, information regarding the genome affinities of species and chromosome pairing behaviour of the hybrids remains almost unknown. The present work analyses the meiotic behaviour of interspecific hybrids by genomic in situ hybridization and cytologically evaluates the genomic relationships among parental species.MethodsEight interspecific F1 hybrids of Paphiopedilum species in various subgenera or sections were investigated in this study. The chromosome behaviour in meiosis of these interspecific hybrids was analysed and subjected to genomic in situ hybridization and fluorescent in situ hybridization.Key ResultsGenomic in situ hybridization was demonstrated as an efficient method to differentiate between Paphiopedilum genomes and to visualize the chromosome pairing affinities in interspecific F1 hybrids, clarifying the phylogenetic distances among these species. Comparatively regular chromosome pairing observed in the hybrids of P. delenatii × P. bellatulum, P. delenatii × P. rothschildianum and P. rothschildianum × P. bellatulum suggested high genomic affinities and close relationships between parents of each hybrid. In contrast, irregular chromosome associations, such as univalents, trivalents and quadrivalents occurred frequently in the hybrids derived from distant parents with divergent karyotypes, such as P. delenatii × P. callosum, P. delenatii × P. glaucophyllum, P. rothschildianum × P. micranthum and P. rothschildianum × P. moquetteanum. The existence of multivalents and autosyndesis demonstrated by genomic in situ hybridization in this study indicates that some micro-rearrangements and other structural alterations may also play a part in differentiating Paphiopedilum species at chromosomal level, demonstrated as different chromosome pairing affinities in interspecific hybrids.ConclusionsThe results indicate that genome homology and the interaction of genetic factors, but not chromosome number nor karyotype similarity, determine the chromosome pairing behaviour in Paphiopedilum hybrids.

Theoretical Determination of One-Electron Redox Potentials for DNA Bases, Base Pairs, and Stacks

Electron affinities, ionization potentials, and redox potentials for DNA bases, base pairs, and N-methylated derivatives are computed at the DFT/M06-2X/6-31++G(d,p) level of theory. Redox properties of a guanine-guanine stack model are explored as well. Reduction and oxidation potentials are in good agreement with the experimental ones. Electron affinities of base pairs were found to be negative. Methylation of canonical bases affects the ionization potentials the most. Base pair formation and base stacking lower ionization potentials by 0.3 eV. Pairing of guanine with the 5-methylcytosine does not seem to influence the redox properties of this base pair much.

English

Comparative banding pattern of the seed protein of 17 taxa belonging to the three families Mimosaceae, Caesalpiniaceae and Fabaceae was studied with the aim of testing the proposed delimitation of the order Leguminales (Fabales) into the three families or subfamilies and to assess the phylogenetic relationships within the three families. Cluster and pairing affinity or similarity index analysis of the data from total protein grouped the 17 taxa into three discrete clusters based on their families. Considerable amount of homology was observed in the banding pattern between the different taxa.   Key words: Cluster analysis, seed protein, Mimosaceae, Caesalpiniaceae, Fabaceae.

Unexpected origins of the enhanced pairing affinity of 2′-fluoro-modified RNA

Various chemical modifications are currently being evaluated for improving the efficacy of short interfering RNA (siRNA) duplexes as antisense agents for gene silencing in vivo. Among the 2′-ribose modifications assessed to date, 2′deoxy-2′-fluoro-RNA (2′-F-RNA) has unique properties for RNA interference (RNAi) applications. Thus, 2′-F-modified nucleotides are well tolerated in the guide (antisense) and passenger (sense) siRNA strands and the corresponding duplexes lack immunostimulatory effects, enhance nuclease resistance and display improved efficacy in vitro and in vivo compared with unmodified siRNAs. To identify potential origins of the distinct behaviors of RNA and 2′-F-RNA we carried out thermodynamic and X-ray crystallographic analyses of fully and partially 2′-F-modified RNAs. Surprisingly, we found that the increased pairing affinity of 2′-F-RNA relative to RNA is not, as commonly assumed, the result of a favorable entropic contribution (‘conformational preorganization’), but instead primarily based on enthalpy. Crystal structures at high resolution and osmotic stress demonstrate that the 2′-F-RNA duplex is less hydrated than the RNA duplex. The enthalpy-driven, higher stability of the former hints at the possibility that the 2′-substituent, in addition to its important function in sculpting RNA conformation, plays an underappreciated role in modulating Watson–Crick base pairing strength and potentially π–π stacking interactions.

Marginal discriminant projections: An adaptable margin discriminant approach to feature reduction and extraction

For pattern analysis and recognition, it is necessary to find the meaningful low-dimensional representation of data in general. In the past decades, subspace learning methods have been regarded as the useful tools for feature extraction and dimensionality reduction. Without loss of generality, the linear subspace learning algorithms can be explained as the enhancement of the affinity and repulsion of several data pairs. Based on this point of view, a novel linear discriminant method, termed Marginal Discriminant Projections (MDP), is proposed to learn the marginal subspace. Rather than the existing marginal learning method, the maladjusted learning problem is alleviated by adopting a hierarchical fuzzy clustering approach, where the discriminative margin can be found adaptively and the iterative objective optimization is avoided. In addition, the proposed method is immune from the well-known curse of dimensionality problem, with respect to the presented subspace learning framework. Experiments on extensive datasets demonstrate the effectiveness of the proposed MDP for discriminative learning and recognition tasks.

Surface plasmon resonance imaging based multiplex biosensor: Integration of biomolecular screening, detection and kinetics estimation

We present a multiplex biosensing method to simultaneously screen targets of interest in a multiple target analyte sample and to extract the binding affinities of all interactant pairs from a single sensor surface using a commercial surface plasmon resonance imaging system. For demonstration, we have prepared our sensor disk with five different ligands varying from low molecular weight antibiotics to high molecular weight human IgG, all immobilized in a microarray format. The multi-target analyte sample was prepared by mixing five antibodies where each one is highly specific for one of the immobilized ligands in a range of concentrations for kinetics estimations. The key advantage of the newly developed approach is that many different types of assays can be performed simultaneously, however, care should be taken to understand the non-specific interactions between different analytes in the sample mixture and unintended ligands, and surface regeneration behavior of different ligand types. Other advantages include reductions in experimental and analysis time, reduced costs, and flexibility since the same microarray can be used for assays with a single target analyte specific for the single ligand.

Gettering of S in Ni from first principles

Sulphur segregation to grain boundaries, surfaces or interfaces seriously degrades the performance of many metallic systems. The addition of appropriate dopants may reduce the sulphur effect. Here we present a first-principles study to provide physical insights into Hf and Pt interactions with S in Ni. The pair affinities are assessed through total energetics, electron localization function and differential charge density analyses. Calculations show that Hf can effectively getter S and hence inhibit S segregation even at high temperatures, while Pt cannot.