New Improved cGMP Analogues to Target Rod Photoreceptor Degeneration

: Retinitis pigmentosa (RP) is a form of retinal degeneration affecting a young population with an unmet medical need. Photoreceptor degeneration has been associated with increased guanosine 3',5'-cyclic monophosphate (cGMP), which reaches toxic levels for photoreceptors. Therefore, inhibitory cGMP analogues attract interest for RP treatments. Here we present the synthesis of dithio-CN03, a phosphorodithioate analogue of cGMP, prepared using the H-phosphonothioate route. Two crystal modifications were identified as a trihydrate and a tetrahydrofuran monosolvates. Dithio-CN03 featured a lower aqueous solubility than its RP-phosphorothioate counterpart CN03, a drug candidate, and this characteristic might be favorable for sustained-release formulations aimed at retinal delivery. Dithio-CN03 was tested in vitro for its neuroprotective effects in photoreceptor models of RP. The comparison of dithio-CN03 to CN03 and its diastereomer SP-CN03, and to their phosphate derivative oxo-CN03 identifies dithio-CN03 as the compound with the highest efficacy in neuroprotection and thus as a promising new candidate for the treatment of RP

Willow short-rotation production systems in Canada and Northern United States: A review

Willow short rotation coppice (SRC) systems are becoming an attractive practice because they are a sustainable system fulfilling multiple ecological objectives with significant environmental benefits. A sustainable supply of bioenergy feedstock can be produced by willow on marginal land using well-adapted or tolerant cultivars. Across Canada and northern U.S.A., there are millions of hectares of available degraded land that have the potential for willow SRC biomass production, with a C sequestration potential capable of offsetting appreciable amount of anthropogenic green-house gas emissions. A fundamental question concerning 1 sustainable SRC willow yields was whether long-term soil productivity is maintained within a multi-rotation SRC system, given the rapid growth rate and associated nutrient exports offsite when harvesting the willow biomass after repeated short rotations. Based on early results from the first willow SRC rotation, it was found willow systems are relatively low nutrient-demanding, with minimal nutrient output other than in harvested biomass. The overall aim of this manuscript is to summarize the literature and present findings and data from ongoing research trials across Canada and northern U.S.A. examining willow SRC system establishment and viability. The research areas of interest presented here are the crop production of willow SRC systems, above- and below-ground biomass dynamics and the C budget, comprehensive soil-willow system nutrient budget, and soil nutrient amendments (via fertilization) in willow SRC systems. Areas of existing research gaps were also identified for the Canadian context