Synthesis and exploration of nucleotide-based prodrugs, signaling molecules and synthetic analogs

In iHEAD, we are developing modified signaling molecules with enhanced biological properties. Recent studies by the Parker group of (Max-Planck Institute for Plant Breeding Research, Cologne) in 2022 revealed two pairs of plant TIR-catalyzed nucleotide-based small molecules (SMs) that were previously unknown in nature. Specific binding of these compounds to EDS1-PAD4 or EDS1-SAG101 dimer complexes, which are intracellular receptors for the SMs, causes an allosteric change in the dimers which promotes their association with a co-functioning nucleotide-binding leucine-rich repeat domain (ADR1 or NRG1) to induce pathogen resistance. We will investigate the action of these compounds on a molecular level. We therefore aim to probe the delivery and localization of the SMs in vitro and in vivo as well as further investigate the mechanism of the protein-protein interaction between the ADR1 or NRG1 domain with the EDS1/PAD4 or EDS1/SAG101 complexes using the natural and modified SM.