Peptide binding by one-armed receptors in water: screening of a combinatorial library for the binding of Val-Val-Ile-Ala.
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Biomedical subjects
Publications and source records attributed to Martin Heil.
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A new class of one-armed tripeptide based cationic guanidiniocarbonyl pyrrole receptors is shown to strongly bind the tetrapeptide L-Val-L-Val-L-Ile-L-Ala, representing the C-terminus of the amyloid beta-peptide even under polar conditions. A medium sized combinatorial library of 125 receptors was synthesized on a solid support and their binding properties determined on bead using a quantitative fluorescence assay. The binding constants are in the order of 10(3)-10(4) M-1 (in the presence of a formate counter ion in methanol) for the most efficient ones but differ by more than a factor of 100 among the 125 library members. Based on the binding data of 12 receptors a structure-stability relationship was established for peptide binding by this new receptor class. Complex formation is controlled by a fine balanced interplay of hydrophobic and electrostatic interactions with none of these two interactions alone being strong enough to ensure complexation under these polar conditions.
The activation energy for the unimolecular dissociation of a non-covalent supramolecular complex between an Artificial Cationic Receptor A ([Gua-Val-Val-Val-Amide]+, in which Gua is guanidiniocarbonyl pyrrole) and an Anionic Tetrapeptide B ([N-Acetyl-Val-Val-Ile-Ala]-) has been determined by measurement of the dissociation rate constant as a function of infrared CO2 laser power density. Singly-charged quasimolecular [A + B + H]+ ions are isolated, stored in a Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer, and irradiated by IR photons. The rate constant for dissociation of the non-covalent complex is determined at five different laser power densities. A plot of the natural logarithm of the first-order rate constant versus the natural logarithm of the laser power density yields a straight line, the slope of which provides an approximate measure of the activation energy (Ea(laser)) for dissociation. Ea(laser) is calculated by a relationship derived earlier by Dunbar and with a newly proposed equation by Paech et al. The results of the two approaches deliver significantly different activation energy values for the unimolecular dissociation of the non-covalent complex. We obtain EaI(laser) = 0.67 eV (Dunbar approximation) and EaII(laser) = 1.12 eV (Paech et al. approximation). Differences between the two approaches are discussed with respect to non-covalent complexes.
Contents of phenolic compounds in leaf extracts often serve as a measure of plant anti-herbivore defence. This method suffers from the multifunctionality of phenolics and from problems with their colorimetric quantification. Here we present further evidence for the pertinence of these problems. Contents of condensed tannins (CCT) were spectrophotometrically quantified in leaf extracts of 11 closely related mimosoid species, and Spodoptera littoralis caterpillars were reared on artificial diet containing these extracts. The relationship of CCT with caterpillar growth differed considerably among plant species, since both positive and negative correlations were detected. There was, however, a negative correlation of CCT with fungal spore germination, indicating a role of these compounds in resistance to fungi. Detailed knowledge on the structure and biological function of defensive compounds and on the overall composition of leaves is required to estimate a plant's defensive efficacy against a particular group of enemies.
Fitness costs can explain the evolution and maintenance of induced resistance in plants. However, the methods currently used to gather evidence for such costs do not allow decreases in fitness to be cleanly attributed to individual traits responsible for induced resistance, because the studies are plagued by multiple confounding responses. Reproductive performance provides an overview of physiological performance and is thus a useful currency to understand the function of induced responses. Integrated molecular, physiological and ecological studies are needed to identify the mechanisms responsible for the decrease in fitness and to evaluate fully the usefulness of the cost paradigm.
There has been rapid progress in detecting the genetic or allocation costs of induced resistance. In addition to these 'internal' costs, ecological costs may result from external mechanisms, that is, from the detrimental effects of resistance on the plant's interactions with its environment. All evolutionarily relevant costs affect a plant's ability to perform under natural conditions. The conceptual separation of different forms of resistance costs simplifies the study of mechanisms by which these costs arise. Yet, integrative measures of fitness must be applied under natural conditions so that researchers can fully understand the costs and benefits of induced resistance.
In a parity judgment task, the ERPs at parietal electrode sites become the more negative the more mental rotation has to be executed. In two experiments, it was investigated whether a temporal relationship exists between the onset of this amplitude modulation and the moment when mental rotation is executed. Therefore, the duration of processing stages located before mental rotation was manipulated. The amplitude modulation was delayed when either the perceptual quality of the stimulus was reduced (Experiment 1) or when character discrimination was more difficult (Experiment 2). The results suggest that the onset of the rotation-related negativity might be used as a chronopsychophysiological marker for the onset of the cognitive process of mental rotation.
In a parity judgment task, the ERPs at parietal electrode sites become more negative as more mental rotation has to be executed. This article provides a review of the empirical evidence regarding this amplitude modulation. More specifically, experiments are reported that validate both the functional relationship between mental rotation and the amplitude modulation as well as the temporal relationship both in single- and in dual-task situations. Additionally, ERP effects are reported in the psychological refractory period (PRP) paradigm with mental rotation as the second task. Finally, unresolved issues are discussed that, I hope, might stimulate future research.
Induced systemic resistance (ISR) of plants against pathogens is a widespread phenomenon that has been intensively investigated with respect to the underlying signalling pathways as well as to its potential use in plant protection. Elicited by a local infection, plants respond with a salicylic-dependent signalling cascade that leads to the systemic expression of a broad spectrum and long-lasting disease resistance that is efficient against fungi, bacteria and viruses. Changes in cell wall composition, de novo production of pathogenesis-related-proteins such as chitinases and glucanases, and synthesis of phytoalexins are associated with resistance, although further defensive compounds are likely to exist but remain to be identified. In this Botanical Briefing we focus on interactions between ISR and induced resistance against herbivores that is mediated by jasmonic acid as a central signalling molecule. While many studies report cross-resistance, others have found trade-offs, i.e. inhibition of one resistance pathway by the other. Here we propose a framework that explains many of the thus far contradictory results. We regard elicitation separately from signalling and from production, i.e. the synthesis of defensive compounds. Interactions on all three levels can act independently from each other.