Recognition Phenomena Research Articles

Urea vs. carbamate groups: a comparative study in a chiral C2 symmetric organogelator.

The effect of the replacement of molecular moieties (carbamates vs. urea) that drive self-assembly for two organogelators with an identical C(2) symmetric molecular structure is described. The main properties of the gels obtained from the urea-based organogelators are also discussed. The proposed organogelators are chiral molecules and are able to express chirality also at the supramolecular level, thus allowing the employment of electronic circular dichroism to gain insight into the molecular-scale structure of fibrillar aggregates. With the same technique, the behavior of enantiomeric mixtures of the urea-based organogelators was investigated, revealing the occurrence of different self-sorting phenomena at the molecular and supramolecular scale. The urea-based organogelators demonstrated to be more efficient gelators with respect to the carbamate-based analogues, showing a high gel-to-sol transition temperature (up to 66 °C) and a very low minimum gelling concentration (0.85 mg mL(-1)). This study is a starting point for a deeper investigation of structure/property relationships and, taking into account the peculiar behavior detected for the enantiomeric mixtures, also of self-sorting and molecular recognition phenomena.

A Novel Approach for Image Recognition to Enhance the Quality of Decision Making by Applying Degree of Correlation Using Artificial Neural Networks

Many diversified applications do exist in science & technology, which make use of the primary theory of a recognition phenomenon as one of its solutions. Recognition scenario is incorporated with a set of decisions and the action according to the decision purely relies on the quality of extracted information on utmost applications. Thus, the quality decision making absolutely reckons on processing momentum and precision which are entirely coupled with recognition methodology. In this article, a latest rule is formulated based on the degree of correlation to characterize the generalized recognition constraint and the application is explored with respect to image based information extraction. Machine learning based perception called feed forward architecture of Artificial Neural Network has been applied to attain the expected eminence of elucidation. The proposed method furnishes extraordinary advantages such as less memory requirements, extremely high level security for storing data, exceptional speed and gentle implementation approach.

Membrane processes for the facilitated extraction of disaccharide sugars: Parameters and mechanism

A supported liquid membrane (SLM) containing a lipophilic agent methyl cholate as carrier, previously used for the facilitated transport of monosaccharides, has been used for the selective extraction of some disaccharides: Lactulose, Lactose, Maltose, Melezitose, Sucrose and Trehalose. The membrane is made of a micro porous poly(vinylidene difluoride) film (PVDF), impregnated with a 0.01M solution of the carrier in xylene. This prepared SLM is remarkably stable for at least 20days. The parameters, permeabilities (P) and initial fluxes (J0) on the facilitated extraction across the studied SLM, for these sugars, were determined. On the basis of the flux dependence on the initial concentrations of carrier and transported substrate, the rate-determining step in the transport mechanism is shown to be the migration of the sugar–carrier complex (ST) in the membrane organic phase. The initial flux of transported sugar is related to the initial concentration of this substrate in feed phase by a saturation law, which has allowed the determination of the parameters, apparent diffusion coefficient D∗ and the association constant Kass of the formed complex (ST) in the SLM organic phase. The results clearly indicate that these all sugar-carrier complexes are unstable, which results in higher coefficients D∗ and thus a high permeability of this membrane type to facilitated extraction of these disaccharides. While, the stability of these complexes varies widely depending on the molecular structure of each disaccharide, confirming the molecular recognition phenomenon by the carrier and can identify interaction sites (substrate–carrier) involved during the extraction these carbohydrates

Indirect readout in protein-peptide recognition: a different story from classical biomolecular recognition.

Protein-peptide interactions are prevalent and play essential roles in many living activities. Peptides recognize their protein partners by direct nonbonded interactions and indirect adjustment of conformations. Although processes of protein-peptide recognition have been comprehensively studied in both sequences and structures recently, flexibility of peptides and the configuration entropy penalty in recognition did not get enough attention. In this study, 20 protein-peptide complexes and their corresponding unbound peptides were investigated by molecular dynamics simulations. Energy analysis revealed that configurational entropy penalty introduced by restriction of the degrees of freedom of peptides in indirect readout process of protein-peptide recognition is significant. Configurational entropy penalty has become the main content of the indirect readout energy in protein-peptide recognition instead of deformation energy which is the main source of the indirect readout energy in classical biomolecular recognition phenomena, such as protein-DNA binding. These results provide us a better understanding of protein-peptide recognition and give us some implications in peptide ligand design.

Structural and energetic insights into the intermolecular interaction among human leukocyte antigens, clinical hypersensitive drugs and antigenic peptides

Immune-mediated adverse drug reactions (ADRs) are one of the most severe drug hypersensitivity syndromes in clinical therapy. As certain drug molecules such as abacavir and carbamazepine have long been known to strongly associate with specific human leukocyte antigen (HLA) alleles to induce an array of adverse immune responses, it is fundamentally important to elucidate the molecular mechanism and biological implication underlying the direct HLA–drug interaction. In this study, a synthetic bioinformatics protocol was used to investigate the recognition and binding phenomenon of drug molecules to their associated HLA alleles. In the procedure, sophisticated molecular docking was performed to determine the intermolecular interactions of drug compounds with HLA proteins, and the resulting scores were then compared with the apparent odds ratio values extracted from clinical data. Some typical HLA–drug complexes with or without antigenic peptides were also subjected to atomistic molecular dynamics simulations, aiming at the understanding of structural details and energetic properties involved in the complex systems. It is suggested that (i) although the theoretical affinities exhibited only a moderate correlation with observed association strengths for unique HLA–drug pairs, the binding orientation and conformation of drug molecules rooting in HLA pockets contributed significantly to eliciting T-cell response and (ii) peptide antigens may play a crucial role in ADR-related HLA–drug recognition and interaction.

Pseudopeptidic cages as receptors for N-protected dipeptides.

The molecular recognition of short peptides is a challenge in supramolecular chemistry, and the use of peptide-like cage receptors represents a promising approach. Here we report the synthesis and characterization of a diverse family of pseudopeptidic macrobicycles, as well as their binding abilities toward N-protected dipeptides using a combination of different techniques (NMR, ESI-MS, and fluorescence spectroscopy). The cage hosts were assayed for dipeptide binding using competition ESI-MS experiments as high-throughput screening to obtain general trends for the recognition phenomena. Selected hosts were additionally studied by NMR spectroscopy ((1)H NMR titration and diffusion-ordered spectroscopy experiments) in different solvents. The results unambiguously demonstrated the formation of the [cage·dipeptide] supramolecular complexes and rendered quantitative information about the strength of the interaction (K(ass)). The structural variables within the pseudopeptidic cage framework that produced a stronger and more selective recognition were thus identified. The cages showed a remarkable selectivity for N-protected dipeptides with an aromatic amino acid at the carboxylic terminus, which prompted us to propose a mode of binding based on polar and nonpolar noncovalent interactions. Accordingly, we faced the molecular recognition of a target dipeptide (Ac-EY-OH) mimicking a biologically relevant sequence by NMR and fluorescence spectroscopy in highly competitive media.

(1R,2S)-Ephedrine: A New Self-Assembling Chiral Template for the Synthesis of Aluminophosphate Frameworks

(1R,2S)-(−)-Ephedrine is used as a new structure-directing agent for the synthesis of nanoporous aluminophosphates. This molecule is selected based on the self-aggregating behavior through π–π type interactions between the aromatic rings and the presence of H-bond-forming groups. Additionally, this molecule possesses two chiral centers, which could enhance a potential transfer of chirality to the inorganic framework. Synthesis results showed that (1R,2S)-(−)-ephedrine is very efficient in directing the crystallization of the AFI-type structure in the presence of several catalytically active dopants. A combination of fluorescence spectroscopy and molecular mechanics simulations shows that ephedrine displays a great trend to self-assemble in water solution, establishing not only π–π type interactions between the aromatic rings but also intermolecular H-bonds between NH2 and OH moieties which compete with the formation of H-bonds with water. These molecules are invariably incorporated as aggregates within the AFI structure, regardless of the dopant introduced, showing a very strong trend to self-assemble within nanoporous frameworks as well. The stability of this supramolecular arrangement within the framework is due to a molecular recognition phenomenon based on the establishment of two H-bonds between the H atoms of the amino group and the O atoms of the hydroxyl group of the consecutive dimer, leading to an infinite supramolecular π–π H-bonded chainlike arrangement within the AFI channels.

Structural and Energetic Determinants of Adhesive Binding Specificity in Type I Cadherins: The Role of Multiple Conformations in Tuning Affinities

Type I Cadherin cell adhesion proteins are similar in sequence and structure and yet are different enough to mediate highly specific cell-cell recognition phenomena. Adhesive dimerization of type I cadherins from apposing cells is mediated by the swapping of N-terminal β-strands between their membrane-distal EC1 domains. It has previously been shown that two prototypic type I family members, E- and N- cadherins, have homophilic dimerization KDs that differ by about an order of magnitude. It has been suggested that this, along with significant heterophilic binding, could account for the differential sorting behavior of cells expressing these cadherins. Here we use a combination of X-ray crystallography, analytical ultracentrifugation, surface plasmon resonance (SPR) and double electron-electron resonance (DEER) spectroscopy to identify the molecular determinants of type I cadherin binding affinities. Small changes in sequence produce subtle structural and dynamical changes that impact dimerization affinities, in part through the generation of bound states involving multiple discrete conformations. These findings highlight the remarkable ability of evolution to exploit a wide range of molecular properties to produce closely related members of the same protein family that have affinity differences finely tuned to mediate their biological roles.

Efficient molecular recognition based on nonspecific van der Waals interaction at the solid/liquid interface.

A highly efficient recognition phenomenon was observed between alkoxylated arylene-ethynylene macrocycles bearing identical side chains but different core size, which is based on van der Waals interactions between alkoxy chains. The ratio of both molecules and the environment of each molecule have been statistically analyzed to quantify the recognition efficiency.

How much do van der Waals dispersion forces contribute to molecular recognition in solution?

The emergent properties that arise from self-assembly and molecular recognition phenomena are a direct consequence of non-covalent interactions. Gas-phase measurements and computational methods point to the dominance of dispersion forces in molecular association, but solvent effects complicate the unambiguous quantification of these forces in solution. Here, we have used synthetic molecular balances to measure interactions between apolar alkyl chains in 31 organic, fluorous and aqueous solvent environments. The experimental interaction energies are an order of magnitude smaller than estimates of dispersion forces between alkyl chains that have been derived from vaporization enthalpies and dispersion-corrected calculations. Instead, it was found that cohesive solvent-solvent interactions are the major driving force behind apolar association in solution. The results suggest that theoretical models that implicate important roles for dispersion forces in molecular recognition events should be interpreted with caution in solvent-accessible systems.

A dry membrane protection technique to allow surface acoustic wave biosensor measurements of biological model membrane approaches.

Model membrane approaches have attracted much attention in biomedical sciences to investigate and simulate biological processes. The application of model membrane systems for biosensor measurements is partly restricted by the fact that the integrity of membranes critically depends on the maintenance of an aqueous surrounding, while various biosensors require a preconditioning of dry sensors. This is for example true for the well-established surface acoustic wave (SAW) biosensor SAM®5 blue. Here, a simple drying procedure of sensor-supported model membranes is introduced using the protective disaccharide trehalose. Highly reproducible model membranes were prepared by the Langmuir-Blodgett technique, transferred to SAW sensors and supplemented with a trehalose solution. Membrane rehydration after dry incorporation into the SAW device becomes immediately evident by phase changes. Reconstituted model membranes maintain their full functionality, as indicated by biotin/avidin binding experiments. Atomic force microscopy confirmed the morphological invariability of dried and rehydrated membranes. Approximating to more physiological recognition phenomena, the site-directed immobilization of the integrin VLA-4 into the reconstituted model membrane and subsequent VCAM-1 ligand binding with nanomolar affinity were illustrated. This simple drying procedure is a novel way to combine the model membrane generation by Langmuir-Blodgett technique with SAW biosensor measurements, which extends the applicability of SAM®5 blue in biomedical sciences.

Engineering of a Cytidine 5′‐Monophosphate‐Sialic Acid Synthetase for Improved Tolerance to Functional Sialic Acids

AbstractSialic acid‐containing glycoconjugates at the cell surface are of high importance in carbohydrate‐mediated recognition phenomena in physiological and pathological events, as well as in bacterial or viral infection. A key step in the enzymatic synthesis of natural sialoconjugates and functional synthetic analogues is the activation of sialic acids to cytidine 5′‐monophosphate (CMP)‐sialic acid intermediates catalyzed by CMP‐sialic acid synthetase (CSS). Based on our recently developed aligned protein model of substrate binding and a simple colorimetric screening assay, we have engineered the CSS from Neisseria meningitidis by structure‐guided site‐specific saturation mutagenesis at positions 192/193 to generate enzymes with broadened substrate scope. Top hits, including the F192S/F193Y variant, display an improvement of up to 70‐fold catalytic efficiency relative to wild‐type CSS for the conversion of sterically demanding N‐acyl modified sialic acid analogues, without compromising protein stability. Such significantly enhanced substrate capacity is a major step forward to realizing a generalized chemo‐enzymatic strategy for the efficient preparation of neo‐sialoconjugate libraries, demonstrated by the highly efficient, regio‐ and stereospecific synthesis of 2,6‐sialyllactose analogues by enzymatic coupling to the highly substrate tolerant α2,6‐sialyltransferase from Photobacterium leiognathi JT‐SHIZ‐145. Our results further document the unusual versatility of the N. meningitidis CSS and engineered variants for a common synthetic approach to sialoconjugates comprising a large diversity of natural and non‐natural sialic acid forms without the need for post‐synthetic enzymatic modification.magnified image

Multicellular Bacteria Deploy the Type VI Secretion System to Preemptively Strike Neighboring Cells

The Type VI Secretion System (T6SS) functions in bacteria as a contractile nanomachine that punctures and delivers lethal effectors to a target cell. Virtually nothing is known about the lifestyle or physiology that dictates when bacteria normally produce their T6SS, which prevents a clear understanding of how bacteria benefit from its action in their natural habitat. Proteus mirabilis undergoes a characteristic developmental process to coordinate a multicellular swarming behavior and will discriminate itself from another Proteus isolate during swarming, resulting in a visible boundary termed a Dienes line. Using transposon mutagenesis, we discovered that this recognition phenomenon requires the lethal action of the T6SS. All mutants identified in the genetic screen had insertions within a single 33.5-kb region that encodes a T6SS and cognate Hcp-VrgG-linked effectors. The identified T6SS and primary effector operons were characterized by killing assays, by construction of additional mutants, by complementation, and by examining the activity of the type VI secretion system in real-time using live-cell microscopy on opposing swarms. We show that lethal T6SS-dependent activity occurs when a dominant strain infiltrates deeply beyond the boundary of the two swarms. Using this multicellular model, we found that social recognition in bacteria, underlying killing, and immunity to killing all require cell-cell contact, can be assigned to specific genes, and are dependent on the T6SS. The ability to survive a lethal T6SS attack equates to “recognition”. In contrast to the current model of T6SS being an offensive or defensive weapon our findings support a preemptive mechanism by which an entire population indiscriminately uses the T6SS for contact-dependent delivery of effectors during its cooperative mode of growth.

ChemInform Abstract: Multivalency in Heterogeneous Glycoenvironments: Hetero‐Glycoclusters, ‐Glycopolymers and ‐Glycoassemblies

AbstractReview: 60 refs.

ChemInform Abstract: Multivalent Glycoliposomes and Micelles to Study Carbohydrate—Protein and Carbohydrate—Carbohydrate Interactions

AbstractReview: 60 refs.

ChemInform Abstract: Di‐ and Trinuclear Copper(II) Complexes of Polyaza Macrocycles and Cryptands as Anion Receptors

AbstractReview: 81 refs.

Electrophoretic profiling and immunocytochemical detection of pectins and arabinogalactan proteins in olive pollen during germination and pollen tube growth

Cell wall pectins and arabinogalactan proteins (AGPs) are important for pollen tube growth. The aim of this work was to study the temporal and spatial dynamics of these compounds in olive pollen during germination. Immunoblot profiling analyses combined with confocal and transmission electron microscopy immunocytochemical detection techniques were carried out using four anti-pectin (JIM7, JIM5, LM5 and LM6) and two anti-AGP (JIM13 and JIM14) monoclonal antibodies. Pectin and AGP levels increased during olive pollen in vitro germination. (1 → 4)-β-d-Galactans localized in the cytoplasm of the vegetative cell, the pollen wall and the apertural intine. After the pollen tube emerged, galactans localized in the pollen tube wall, particularly at the tip, and formed a collar-like structure around the germinative aperture. (1 → 5)-α-l-Arabinans were mainly present in the pollen tube cell wall, forming characteristic ring-shaped deposits at regular intervals in the sub-apical zone. As expected, the pollen tube wall was rich in highly esterified pectic compounds at the apex, while the cell wall mainly contained de-esterified pectins in the shank. The wall of the generative cell was specifically labelled with arabinans, highly methyl-esterified homogalacturonans and JIM13 epitopes. In addition, the extracellular material that coated the outer exine layer was rich in arabinans, de-esterified pectins and JIM13 epitopes. Pectins and AGPs are newly synthesized in the pollen tube during pollen germination. The synthesis and secretion of these compounds are temporally and spatially regulated. Galactans might provide mechanical stability to the pollen tube, reinforcing those regions that are particularly sensitive to tension stress (the pollen tube-pollen grain joint site) and mechanical damage (the tip). Arabinans and AGPs might be important in recognition and adhesion phenomena of the pollen tube and the stylar transmitting cells, as well as the egg and sperm cells.

Small Molecules as Chromatographic Tools for HPLC Enantiomeric Resolution: Pirkle-Type Chiral Stationary Phases Evolution

This review focuses on the evolution of Pirkle-type chiral stationary phases (CSPs), based on chiral recognition mechanism of small molecules and applications directly related with Medicinal Chemistry. Therefore, the strategies to plan these chiral selectors for enantioseparation of diverse therapeutic classes of chiral drugs and the understanding of the recognition mechanism are emphasized. The planning of Pirkle and co-workers to design different classes of CSPs was initially based on NMR studies, following the principle of reciprocity together with chromatographic results and studies of chiral recognition phenomena. All those features are described and critically discussed in this review. Finally, based on general principles established by Pirkle’s work it can be inferred that diverse chiral small molecules can be successfully used as chromatographic tools for enantiomeric resolution. In this context, several research groups were inspired on Pirkle’s design to develop new CSPs. Xanthone derivatives bonded to chiral groups were also exploited as selectors for CSPs and are briefly reported.

The structure Biology and Application of Phytohemagglutinin (PHA) in Phytomedicine: With special up-to-date references to lectins

Lectins first discovered more than 100 years ago in plants, they are now known to be present throughout nature. Phytohemagglutinin (PHA), the lectin extract from the red kidney bean (Phaseolus Vulgaris), contain potent, cell agglutinating and mitogenic activities. They play a role in biological recognition phenomena involving cells and proteins towards medical applications. The present article is a brief review of the history of lectin in nature. By reviewing the web-based search for all types of peer review articles published, was initiated using ISI web of Sciences and Medline / PubMed, and other pertinent references on websites about lectins. Here, we present a brief account of 100-plus years of lectin research and show how these proteins have become the focus of intense interest for biologists and in particular for the research and applications in medicine. Phytohemagglutinin, has been widely used for mitotic stimulation to human lymphocytes, cell arrest, or apoptosis, potential sources for developing novel pharmaceutical preparation and intensive interest for health care services, biologist and phytomedicine research can be considered.

Aqueous Self-Sorting in Extended Supramolecular Aggregates

Self-organization and self-sorting processes are responsible for the regulation and control of the vast majority of biological processes that eventually sustain life on our planet. Attempts to unveil the complexity of these systems have been devoted to the investigation of the binding processes between artificial molecules, complexes or aggregates within multicomponent mixtures, which has facilitated the emergence of the field of self-sorting in the last decade. Since, artificial systems involving discrete supramolecular structures, extended supramolecular aggregates or gel-phase materials in organic solvents or—to a lesser extent—in water have been investigated. In this review, we have collected diverse strategies employed in recent years to construct extended supramolecular aggregates in water upon self-sorting of small synthetic molecules. We have made particular emphasis on co-assembly processes in binary mixtures leading to supramolecular structures of remarkable complexity and the influence of different external variables such as solvent and concentration to direct recognition or discrimination processes between these species. The comprehension of such recognition phenomena will be crucial for the organization and evolution of complex matter.