ASIT Biotech (Belgium)

In this study, the aim is to develop a population model based approach to optimize fruit harvesting strategies with regard to fruit quality and its derived economic value. This approach was applied to the case of tomato fruit harvesting under Vietnamese conditions. Fruit growth and development of tomato (cv. “Savior”) was monitored in terms of fruit size and color during both the Vietnamese winter and summer growing seasons. A kinetic tomato fruit growth model was applied to quantify biological fruit-to-fruit variation in terms of their physiological maturation. This model was successfully calibrated. Finally, the model was extended to translate the fruit-to-fruit variation at harvest into the economic value of the harvested crop. It can be concluded that a model based approach to the optimization of harvest date and harvest frequency with regard to economic value of the crop as such is feasible. This approach allows growers to optimize their harvesting strategy by harvesting the crop at more uniform maturity stages meeting the stringent retail demands for homogeneous high quality product. The total farm profit would still depend on the impact a change in harvesting strategy might have on related expenditures. This model based harvest optimisation approach can be easily transferred to other fruit and vegetable crops improving homogeneity of the postharvest product streams.

BackgroundInterleukin-7 receptor alpha (IL-7Rα) represents a biomarker with potential applications in rheumatoid arthritis (RA) diagnosis and therapy. We have therefore searched by phage display potential IL-7Rα specific peptides with the primary goal being to develop in vivo molecular imaging tools.MethodsIL-7Rα-targeted peptides were searched within a disulfide-constrained combinatorial phage displayed library of random linear heptapeptides. The apparent dissociation constant (Kd) and half maximal inhibition constant (IC50) were estimated for phage clones and synthesized peptides by ELISA. We used 5-Aza-2’-deoxycytidine (ADC)-stimulated Jurkat cells and human synovial tissue from patients with RA for in vitro characterization of peptides. For molecular imaging studies performed by magnetic resonance imaging (MRI), experimental arthritis was induced in DBA/1 male mice by immunization with an emulsion of complete Freund’s adjuvant and type II collagen from chicken sternal cartilage.ResultsAfter several steps of phage display and peptide screening, two IL-7Rα-specific heptapeptides (P258 and P725) were selected from the initial library, based on their affinity for the target (extracellular domain of IL-7Rα, which contains a fibronectin type III repeat-like sequence). P258 (a linear peptide obtained by removing the Cys-constraint) had the lowest affinity for fibronectin itself and was therefore proposed for molecular imaging. After grafting to ultra-small superparamagnetic particles of iron oxide (USPIO), P258 produced a strong negative contrast on MRI in mice with collagen-induced arthritis (CIA), even at 2 hours post injection. The co-localization of USPIO-P258 with IL-7Rα-expressing cells in the synovial tissue from CIA mice and its ability to discriminate the level of IL-7R expression and the disease severity confirmed its efficacy as an in vivo IL-7Rα imaging agent. Interestingly, the cyclic peptide (P725), which was less adequate for molecular imaging because of higher affinity for fibronectin, had a strong ability to compete with IL-7 for the IL-7Rα binding sites, making it a potential candidate for blocking applications. Accordingly, P725 prevented the signal transducer and activator of transcription 5 (STAT5) activation induced by IL-7 in ADC-stimulated Jurkat cells.ConclusionsThe two peptides identified in this work demonstrate that IL-7Rα targeting in RA presents potential applications for in vivo molecular imaging and putative blocking purposes.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-016-1133-8) contains supplementary material, which is available to authorized users.

Abstract Recent data in a number of tumour types has implicated Fibroblast Growth Factor (FGF) and Fibroblast Growth Factor receptor (FGFr) signalling as being key to the molecular pathology of cancer. This poster will describe fragment based drug discovery using biophysical screening to identify initial fragments. Subsequently, in the fragments-to-leads stage a detailed structural understanding of the binding interactions between the fragment and its target protein utilised X-ray crystallography and NMR. Starting with different fragments allows several lead series to be identified, often by synthesizing only small numbers of compounds. A fragment screening campaign was conducted against the FGFr-1 to detect very low molecular weight compounds that bound to the hinge region of the kinase. The screening produced several fragment molecules (Molecular Weight <250 Da) which were in the micromolar range and confirmed binding mode in X-ray crystallography. One X-ray hit series that was 120 uM verse FGFr-3 will be described. Several iterations of structure-guided medicinal chemistry led to the identification of a lead compound with 3 nM affinity for FGFr-3, good cell activity and 30-fold selectivity verse VEGFr-2 with good oral activity. The lead was optimised to afford a compound that showed good PK/PD and efficacy. This poster represents first disclosure of the structure of the lead series and illustrates how a fragment-based drug discovery approach can be efficiently used to discover compounds advanced nanomolar compounds with oral bioavailability. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5778.