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Alexandra Hauser-Kawaguchi Cornelia Tolg Teresa Peart Mark Milne Eva A. Turley Leonard G. Luyt 《Bioorganic & medicinal chemistry》2018,26(18):5194-5203
The receptor for hyaluronan mediated motility (RHAMM, gene name HMMR) belongs to a group of proteins that bind to hyaluronan (HA), a high-molecular weight anionic polysaccharide that has pro-angiogenic and inflammatory properties when fragmented. We propose to use a chemically synthesized, truncated version of the protein (706–767), 7?kDa RHAMM, as a target receptor in the screening of novel peptide-based therapeutic agents. Chemical synthesis by Fmoc-based solid-phase peptide synthesis, and optimization using pseudoprolines, results in RHAMM protein of higher purity and yield than synthesis by recombinant protein production. 7?kDa RHAMM was evaluated for its secondary structure, ability to bind the native ligand, HA, and its bioactivity. This 62-amino acid polypeptide replicates the HA binding properties of both native and recombinant RHAMM protein. Furthermore, tubulin-derived HA peptide analogues that bind to recombinant RHAMM and were previously reported to compete with HA for interactions with RHAMM, bind with a similar affinity and specificity to the 7?kDa RHAMM. Therefore, in terms of its key binding properties, the 7?kDa RHAMM mini-protein is a suitable replacement for the full-length recombinant protein. 相似文献
104.
W. M. Milne 《BioControl》1997,42(1-2):173-183
The spotted alfalfa aphid (SAA),Therioaphis trifolii (Monell)f. maculata, was first recorded in Australia in 1977. It is a major pest of lucerne and other pasture medics but not of clover (Trifolium spp.). The parasitoidTrioxys complanatus Quilis was introduced into Australia in late 1977 as part of a biological control program for SAA and made a substantial contribution to the management of the pest. Since 1989, aphids which are individually indistinguishable from SAA have been causing substantial yield loss to clover pastures in western and south-eastern Australia. This aphid, now known in Australia as the spotted clover aphid (SCA), is genetically distinct from SAA and has a much wider host range. Populations of SCA in clover are rarely parasitised byT. complanatus. A series of experiments was undertaken to determine whether the greater susceptibility of SAA in lucerne than of SCA in clover to parasitisation byT. complanatus is due to the attraction of the parasitoid preferentially to lucerne or to the differential attractiveness of the aphids themselves. SAA and SCA were offered to the parasitoids in arenas of increasing complexity from single trifoliate leaves of lucerne and clover on agar through single potted plants in small cages to groups of potted plants in a large cage. Results showed that the parasitoids exhibited a preference for lucerne though, in the cage situation, they did find and parasitise SCA on clover. They did not differentiate between SAA and SCA on lucerne. 相似文献
105.
A model of the effect of fungicides on disease-induced yield loss, for use in wheat disease management decision support systems 总被引:1,自引:0,他引:1
A model of the effect of foliar-applied fungicides on disease-induced yield loss is described, parameterised and tested. The effects of fungicides on epidemics of Septoria tritici (leaf blotch), Puccinia striiformis (yellow rust), Blumeria graminis f.sp. tritici (powdery mildew) and Puccinia triticina (brown rust) on winter wheat were simulated using dose–response curve parameters. Where two or more active substances were applied together, their joint action was estimated using an additive dose model where the active substances had the same mode of action or a multiplicative survival model where the modes of action differed. By coupling the model with models of wheat canopy growth and foliar disease published previously, it was possible to estimate disease-induced yield loss for a prescribed fungicide programme. The difference in green canopy area and, hence, interception of photosynthetically active radiation between simulated undiseased and diseased (but treated) crop canopies was used to estimate yield loss. The model was tested against data from field experiments across a range of sites, seasons and wheat cultivars and was shown to predict the observed disease-induced yield loss with sufficient accuracy to support fungicide treatment decisions. A simple method of accounting for uncertainty in the predictions of yield loss is described. Fungicide product, dose and spray timing combinations selected using the coupled models responded appropriately to disease pressure and cultivar disease resistance. 相似文献
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Mariann M. Gabrawy Reyhan Westbrook Austin King Nick Khosravian Neeraj Ochaney Tagide DeCarvalho Qinchuan Wang Yuqiong Yu Qiao Huang Adam Said Michael Abadir Cissy Zhang Pratik Khare Jennifer E. Fairman Anne Le Ginger L. Milne Fernando J. Vonhoff Jeremy D. Walston Peter M. Abadir 《Aging cell》2024,23(4):e14102
Tryptophan catabolism is highly conserved and generates important bioactive metabolites, including kynurenines, and in some animals, NAD+. Aging and inflammation are associated with increased levels of kynurenine pathway (KP) metabolites and depleted NAD+, factors which are implicated as contributors to frailty and morbidity. Contrastingly, KP suppression and NAD+ supplementation are associated with increased life span in some animals. Here, we used DGRP_229 Drosophila to elucidate the effects of KP elevation, KP suppression, and NAD+ supplementation on physical performance and survivorship. Flies were chronically fed kynurenines, KP inhibitors, NAD+ precursors, or a combination of KP inhibitors with NAD+ precursors. Flies with elevated kynurenines had reduced climbing speed, endurance, and life span. Treatment with a combination of KP inhibitors and NAD+ precursors preserved physical function and synergistically increased maximum life span. We conclude that KP flux can regulate health span and life span in Drosophila and that targeting KP and NAD+ metabolism can synergistically increase life span. 相似文献
109.
Roslyn Lefin Mietha M. van der Walt Pieter J. Milne Gisella TerreBlanche 《Bioorganic & medicinal chemistry letters》2017,27(17):3963-3967
Previous research has shown that bicyclic 6:5-fused heteroaromatic compounds with two N-atoms have variable degrees of adenosine A1 receptor antagonistic activity. Prompted by this imidazo[1,2-α]pyridine analogues were synthesized and evaluated for their adenosine A1 and A2A receptor affinity via radioligand binding studies and subjected to a GTP shift assay to determine its adenosine A1 receptor agonistic or antagonistic functionality. Imidazo[1,2-α]pyridine, the parent scaffold, was found devoid of affinity for the adenosine A1 and A2A receptors. The influence of substitution on position C2 showed no improvement for either adenosine A1 or A2A receptor affinity. The addition of an amino or a cyclohexylamino group to position C3 also showed no improvement of adenosine A1 or A2A receptor affinity. Surprisingly para-substitution on the phenyl ring at position C2 in combination with a cyclohexylamino group at position C3 led to adenosine A1 receptor affinity in the low micromolar range with compound 4d showing: (1) the highest affinity for the adenosine A1 receptor with a Ki value of 2.06 µM and (2) adenosine A1 receptor antagonistic properties. This pilot study concludes that para-substituted 3-cyclohexylamino-2-phenyl-imidazo[1,2-α]pyridine analogues represent an interesting scaffold to investigate further structure-activity relationships in the design of novel imidazo[1,2-α]pyridine-based adenosine A1 receptor antagonists for the treatment of neurodegenerative disorders. 相似文献
110.
White rot fungi (WRF) are applicable to biodegradation of recalcitrant pollutants. However, excessive biomass growth typical for WRF cultivation can hinder their large scale applications. Therefore, immobilization of Irpex lacteus to liquid-core alginate beads restricting excessive mycelium growth and simultaneously keeping high degradation rate of pollutants was tested. Effective diffusivities of dyes to the beads varied from (2.98 ± 0.69) × 10?10 to (10.27 ± 2.60) × 10?10 m2/s. Remazol Brilliant Blue R (RBBR), Reactive Orange 16 (RO16), and Naphthol Blue Black (NBB) were used as model dyes. The immobilized fungus decolorized model dyes when applied both in microwell plates and in fluidized bed reactors. Using the microwell plates, the apparent reaction rate constants ranged from (2.06 ± 0.11) × 10?2 to (11.06 ± 0.27) × 10?2 1/h, depending on the dye used and its initial concentration. High initial concentrations negatively affected the dye decolorization rate. No fungal growth outside the beads was observed in fluidized bed reactors and thus no operational problems linked to an excessive biomass growth occurred. When RBBR was decolorized in subsequent batches in the fluidized bed reactor, the apparent reaction rate constant increased from (11.63 ± 0.35) × 10?2 to (29.26 ± 7.19) × 10?2 1/h. 相似文献