Drought Stress Relief
Amongst abiotic stresses, drought stress is one of the main sources of crop loss around the globe. One protection strategy is the development of chemicals that help crops cope with water deficiency. Using a natural plant hormone as their starting point, Jens Frackenpohl, Bayer AG, CropScience Division, Frankfurt am Main, Germany, and colleagues have identified several analogues that are highly effective against drought stress. The team also gained new insights into the structure-activity relationship of the hormone.
The plant hormone they used is called abscisic acid (ABA) and plays a key role in physiological processes such as seed maturation and seed dormancy. It has been commercialized for uses such as enhancing color development in red table grapes. In addition, it is known for its ability to promote the adaption of plants to environmental stresses such as drought or salinity stress.
Analogues of Abscisic Acid
ABA consists of two distinct structural parts: a cyclohexenone headgroup and a terpenoid side chain, both equipped with specific structural motifs. Inspired by structural features from earlier agrochemical projects and from in vivo experiments showing promising efficacy against drought stress, the team carried out molecular modeling studies looking for new head group variations that might dock well into the binding pocket of a physiological ABA receptor protein.
The researchers developed flexible synthetic approaches based on Stille or Sonogashira cross-coupling reactions. These reactions are key steps for joining the two building blocks together by connecting two carbon atoms. Their route enabled the researchers to synthesize several series of ABA analogues for their biological and biochemical tests.
Cyano-Cyclopropyl Groups as Promising Replacements
As one major achievement, the researchers identified a headgroup bearing a cyano-cyclopropyl moiety that proved to be a suitable replacement of ABA’s cyclohexenone unit. They connected this new headgroup to different side chains and carried out in vitro binding studies with the ABA receptor. In addition, the compounds were sprayed onto the leaves of crop plants under drought stress conditions. In total, the team identified several highly potent analogues of ABA with improved in vivo efficacy against drought stress in canola and wheat.
In a further study, the scientists systematically explored a broad variety of side chain modifications to gain new insights into structure–activity relationships of the hormone. Results from in vitro measurements and crystal structure analyses confirmed a cavity of limited size in the ABA-receptor, which accepts only small substituents. Based on these results, they identified various additional new analogues of ABA with improved in vivo efficacy against drought stress in canola and wheat. The team also observed promising effects in corn and barley.
- Potent Analogues of Abscisic Acid – Identifying Cyano-Cyclopropyl Moieties as Promising Replacements for the Cyclohexenone Headgroup,
Jens Frackenpohl, Guido Bojack, Rachel Baltz, Udo Bickers, Marco Busch, Jan Dittgen, Jana Franke, Jörg Freigang, Erwin Grill, Susana Gonzalez, Hendrik Helmke, Martin J. Hills, Sabine Hohmann, Pascal von Koskull-Döring, Jochen Kleemann, Gudrun Lange, Stefan Lehr, Dirk Schmutzler, Arno Schulz, Kerstin Walther, Lothar Willms, Christian Wunschel,
Eur. J. Org. Chem. 2018, 2018, 1416–1425.