Plant diseases account for 15% crop loses worldwide (1), presenting a significant economic, environmental, and social challenge in a world facing increased demands on food, fibre and biofuels. The activation of innate immune signalling in both plants and animals is mediated by nucleotide-binding leucine-rich repeat receptors (NLRs). NLRs enable the specific identification of pathogen effectors, leading to the initiation of ETI (2). Although genetic tools are available to study ETI in some plant species, very few small molecule reagents (chemical probes) have been reported (3,4). Recently, several signalling nucleotides unique to plants are derived from the essential metabolite nicotinamide adenine dinucleotide (NAD+) were identified as secondary messengers that interact with specific nucleotide receptors to activate ETI (5,6), which now opens the way for developing a chemical toolbox to study and manipulate ETI and establish if ETI modulation by small molecules can be used as a crop protecting strategy.
A major limitation of nucleotides for use inside cell is that they often are metabolically unstable and have poor membrane permeability. Critically, the interactions between ETI activating nucleotides and their receptors have not been characterised in detail and the relationship between their chemical structures and their ability to induce ETI are not well understood. In this presentation, stereoselective concise synthesis of pRib-AMP, its derivatives and their evaluation as metabolically stable and cell-permeable nucleotide modulators of ETI will be presented.