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Neonicotinoids are emerging as a major class of insecticides with promising insecticidal activity having a specific affinity towards the nicotinic acetylcholine receptors (nAChR). A quantitative structure-activity relationship (QSAR) study was performed on some azidopyridinyl neonicotinoids for their selective insecticidal activity over mammalian toxicity. The result showed that increased surface area of the molecules may help to increase the binding affinity of the compounds towards the Drosophila receptor and the presence of the azido group on the other hand may be detrimental towards the affinity. Compounds having low polarity, increased probability of nucleophilic attack at the particular position (N-1), and a higher positive charge at the C-12 position can reduce the binding affinity of these compounds towards the mammalian receptor. Key words: QSAR, neonicotinoids, Drosophila nicotinic receptor, mammalian [α.sub.4][β.sub.2] receptor, AM1. Les neonicotinoides emergent comme une classe majeure de composes possedant une activite insecticide interessante et une activite specifique pour les recepteurs de l'acetylcholine nicotinique (<>). Une etude de relation structure-activite quantitative (RSAQ) a ete realisee sur quelques neonicotinoides de l'azidopyridinyle pour evaluer leur activite insecticide selective sur la toxicite mammifere. Le resultat montre que la superficie accrue de la surface des molecules pourrait eventuellement leur permettre d'augmenter les affinites de fixation des composes sur le recepteur Drosophila alors que, par ailleurs, la presence du groupe azido pourrait nuisible a cette affinite. Les composes de faible polarite augmentent la probabilite d'une attaque nucleophile a la position particuliere (N-1) et d'une charge plus positive en position C-12 et peuvent reduire l'affinite de fixation de ces composes vis-a-vis des recepteurs mammiferes. Mots cles : RSTQ, neonicotinoides, recepteur nicotinique Drosophila, recepteur mammifere [α.sub.4][β.sub.2], AM1. [Traduit par la Redaction], Introduction The neonicotinoids (1) are one of the major classes of insecticides, having very promising potency (2). They are nicotinic agonists that interact with nicotinic acetylcholine receptors (nAChR) in a [...]

A study was conducted to determine structural aspects of Melanocortin-3 receptor responsible for ligand binding and receptor signaling. The results provide important information about the molecular determinants of human melanocortin-3 receptor ligand-receptor (hMC3R) responsible for ligand binding and receptor signaling.

Extracellular signals are transmitted to cells through two classes of cell-surface receptors: signaling receptors that directly transduce signals and signaling co-receptors that bind ligand but that, traditionally, have not been thought to signal directly. Signaling co-receptors modulate the ligand binding and signaling of their respective signaling receptors. In recent years, roles for co-receptors have expanded to include essential functions in morphogen gradient formation, localizing signaling, signaling independently, regulating cell adhesion and orchestrating the signaling of several pathways. The importance of signaling co-receptors is demonstrated by their ubiquitous expression, their conservation during evolution, their prominent role in signaling cascades, their indispensable role during development and their frequent mutation or altered expression in human disease.

A series of internal deletion mutants of the vitamin D receptor (VDR) hinge is generated and found that deletion of a few as five amino acids from the C-terminus of the hinge significantly reduces transcriptional activation in vivo. The ability to delete more of the RxR hinge may be related to the additional plasticity required by its role as the common hetereodimer partner for nuclear receptors on differing DNA elements.

A N,N-(dimethylamino)pyridine monomer is incorporated into the backbone of a m-phenyleneethynyleen oligomer such that the pyridine nitrogen is located on the interior surface of the binding cavity in the folded structure of the oligomer. By comparison of k(sub u) for the 13-mer with the second-order rate constant for a 3-mer that is too short to fold and thus unable to bind methyl iodide the effective morality is calculated to be 230 M.

The way in which the perception of G protein-coupled receptor (GPCR) oligomerization has progressed and changed over the years, and the potential significance of Oligomerization to the mechanism of G protein-mediated signaling is presented. It is concluded that the organization of GPCR's into complex containing multiple equivalents of both receptor and G protein provides a platform for various cooperative effects and may allow for a form of fine control in GPCR-mediated signaling.

A specific agonist of the endothelin-B receptor subtype (ET(sub B)), a few photosensitive analogues is developed to investigate the binding domain of the receptor. Using the photoaffinity-labeling technique, a key segment of the ET(sub B) receptor participating in the interaction with the ET-1 of IRL-1620 ligands is identified.

The use of cyclic peptides in the selection of single-chain (ScFv) antibodies specific for the HIV-1 coreceptor CCR5, a representative G-protein-coupled receptor (GPCR) is described. Results illustrate that surface-antigen mimetics of a GPCR are effective tools for selecting active, site-specific ScFv antibodies that hold promise as immunological reagents and therapeutics.

Characterization of nine consecutive residues in a transmember segment of the proposed Beta-strand of the ferric enterobactin receptor FepA active site loop through electron paramagnetic resonance (EPR) site-directed spin-labeling found that the residues adopt a Beta-strand secondary structure bridging the lipid bilayer. Alternate residues fact the lipid alkyl chains and the aqueous interior of the channel. Strong tertiary interactions in the extracellular half of the strand suggest strand-loop interactions.

Synthesis and examination of disaccharide polyphosphates based upon adenophostin A revealed that all analogs mobilized the same intracellular Ca2+ pool as Ins(1,4,5)P3 and adenophostin A but none was as potent as adenophostin A. Results indicate that Rib(2,3',4')P3 is as potent as Ins(1,4,5)P3, more potent than most inositol-based agoninsts, but is not as potent than adenophostins. Data show that phophorylated disaccharides provide for the development of high affinity ligands of Ins(1,4,5)P3 receptors.

An investigation of the importance of B-loop sequences in determining receptor activation has been conducted. The study also sought to understand their causal role in the antagonistic activity of the Argos ligand. The results showed that a number of nonconservative substitution in the human epidermal growth factor B-loop are tolerated without any effect on receptor binding or activation. They also indicate that both receptor binding and signaling efficiency can be uncoupled, a prerequisite for receptor antagonist development.

Neutrophils use a variety of cell-surface receptors for attachment to surfaces, such as the endothelium or opsonized pathogens. During inflammation or infection, chemoattractants or cytokines bind to neutrophils and upregulate or 'prime' their responsiveness. Priming can increase the number of some receptors expressed on the cell surface but can also change receptor function, so that the receptor has altered ligand-binding properties or becomes linked to new intracellular signalling systems.

The numerous and widespread effects of adenosine provide both an opportunity for the development of novel therapeutic agents acting via adenosine receptors and the challenge of achieving selectivity of action. The feasibility of achieving selectivity is enhanced if receptor subtypes can be identified. Biochemical, functional and receptor-cloning studies are beginning to provide convergent data supporting the existence of A(sub 1), A(sub 2A), A(sub 2B) and A(sub 3) receptors. However, studies of the functional significance of these receptors in intact tissues both in vitro and in vivo have lagged behind the biochemical studies. In this article, Michael Collis and Susanna Hourani review the current status of adenosine receptor classification and propose that ligands with greater selectivity need to be evaluated in a wide range of functional preparations if the therapeutic potential of this area is to be realized.

The availability of catalytic sequences was examined using anti-peptide antibodies generated against highly conserved sites in the kinase domain and two nonconserved sequences around autophosphorylation sites in the epidermal growth factor receptor (EGFR) carboxyl-terminal domain. Results revealed that only alphaHRD and alphaDFG had an inhibitory effect on EGFR kinase activity, suggesting that the sites HRD and DFG were involved in catalysis. Except for that found in the HRD site, all epitopes were found to be exposed to antibody binding.

A comparative study was conducted on the dynamic conformations of the immunoglobulin (Ig) isotopes murine IgE and human IgG1. Results show that both Ig have a carboxy-terminal domain. The average end-to-end distance for both Ig were also determined. IgG1 in solution displayed more flexibility than IgE and this was attributed to IgG1's shorter average end-to-end distance measurement.

A study was conducted on the phenomenon of ligand mimicry by anti-receptor antibodies. The generation and properties of the anti-receptor antibodies that react with the ligand binding site were analyzed and were found to have vital structural and therapeutic implications. Similar amino acids and side-chain geometries were found to be useful for reovirus type 3 and influenza hemagglutinins in their interactions with cell-surface receptors. The peptide and nonpeptide mimetics can also be therapeutically useful in cases such as treatment of thyroid disease and hypercoagulation states.

A study was conducted to understand why it is hard to design a high-affinity receptor and to explore the limits of affinity, with bioactive peptide RGD as a model ligand was conducted. The analysis of the computed efficiencies suggested that a low molecular weight receptor could achieve protein like affinity.

Cholapod anion receptors are capable of high affinities while retaining compatibility with nonpolar organic media. Among the 13 receptors studied, the structures include between three and six H-bond donors sited in urea, thiourea, sulfonamide, carbamate, trofluoroacetamide and isophthalamide binding units.

The binding of mono- and bivalent forms of the receptors B cell maturation protein (BCMA) and B cell activating factor of the TNF family (BAFF) receptor, BAFFR to BAFF and a proliferation-inducing ligand, APRIL are characterized. The quantitative assessment of the affinity of receptor binding to each ligand is made possible by using soluble, mono- and bivalent forms of these candidate receptors.

A simple, efficient, and general method is demonstrated to form heterodimeric nanostructures based on the reactions on the colloidosome, offering easy access to multifunctional heterodimers that are hydrophilic, fluorescent, responsive to magnetic forces, and able to bind to specific receptors. The procedure not only controls the sizes and compositions of nanoparticle heterodimers but also allows functional molecules to be attached on specific parts of the heterodimers.

The study demonstrates a new computational approach, which helps in the increase of the complex binding relationships with atomic details. It neither needs synthesis and purification of proteins nor requires mutagenesis, and is not influenced by the size of the molecules.