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Abstract: Melanocortin MC3 and MC4 receptor agonists have pharmaceutical benefit in the regulation of energy homeostasis. These agonists are defined by two parameters, their potency and their efficacy. However, these parameters are dependent upon the system in which they are measured. Herein, we have used the operational model of agonism to define agonist properties. We have used two different assay formats, cAMP accumulation and a cAMP response element (CRE)-β-lactamase gene reporter to measure melanocortin MC3 and MC4 receptor agonist profiles, in the presence and absence of the irreversible receptor inactivator N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) and fitted these data to the operational model of agonism to define agonist affinity and efficacy. Data generated using the cAMP accumulation assay fitted well to assumptions made in the operational model and provided estimations of affinity and efficacy in line with those expected. However, data generated in the gene reporter assays showed over a 100-fold increase in agonist affinity compared with cAMP data and unexpectedly low values for efficacy. These data show that the operational model can be used to determine the efficacies of melanocortin agonists which appear as full agonists in cAMP assays, but that this is not the case for gene reporter assays in which agonist efficacies cannot be distinguished. [Copyright &y& Elsevier]

The chemical industry is increasingly looking to develop bio-based alternatives to petroleum-based platform chemicals, in order to reduce dependence on diminishing fossil resources and to decrease GHG emissions. 5-Hydroxymethylfurfural (HMF) and 2,5-furandicarboxylic acid (FDCA) are two examples of bio-based chemicals which could allow for the synthesis of a wide range of chemicals and materials, particularly polymers, from renewable feedstocks. This review paper summarises and critically evaluates results from existing life cycle assessment (LCA) and technoeconomic analysis (TEA) studies of HMF and FDCA synthesis and, by doing this, provides several points of advice for future investigations and assessments of synthetic routes towards these bio-based products. Chemical considerations such as choice of solvent system, catalyst and energy production are reviewed; and methodological issues in LCA, such as treatment of biogenic carbon and allocation methods, are discussed. Overall, results suggest that the production of HMF and FDCA-based products may offer lower impacts from CO2 emissions than their fossil-based counterparts, but this often comes with an increase in environmental impacts in other impact categories. Higher operating costs from expensive fructose feedstocks and high energy demands also make HMF and FDCA less economically viable than current chemicals. Moving forwards, further investigation into different lignocellulosic feedstocks, energy production units and the development of new catalytic systems may help in making HMF and FDCA production more favourable than the production of fossil-based counterparts. [ABSTRACT FROM AUTHOR]