The First Structure–Activity Relationship Studies for Designer Receptors Exclusively Activated by Designer Drugs

[Image: see text] Over the past decade, two independent technologies have emerged and been widely adopted by the neuroscience community for remotely controlling neuronal activity: optogenetics which utilize engineered channelrhodopsin and other opsins, and chemogenetics which utilize engineered G protein-coupled receptors (Designer Receptors Exclusively Activated by Designer Drugs (DREADDs)) and other orthologous ligand–receptor pairs. Using directed molecular evolution, two types of DREADDs derived from human muscarinic acetylcholine receptors have been developed: hM3Dq which activates neuronal firing, and hM4Di which inhibits neuronal firing. Importantly, these DREADDs were not activated by the native ligand acetylcholine (ACh), but selectively activated by clozapine N-oxide (CNO), a pharmacologically inert ligand. CNO has been used extensively in rodent models to activate DREADDs, and although CNO is not subject to significant metabolic transformation in mice, a small fraction of CNO is apparently metabolized to clozapine in humans and guinea pigs, lessening the translational potential of DREADDs. To effectively translate the DREADD technology, the next generation of DREADD agonists are needed and a thorough understanding of structure–activity relationships (SARs) of DREADDs is required for developing such ligands. We therefore conducted the first SAR studies of hM3Dq. We explored multiple regions of the scaffold represented by CNO, identified interesting SAR trends, and discovered several compounds that are very potent hM3Dq agonists but do not activate the native human M3 receptor (hM3). We also discovered that the approved drug perlapine is a novel hM3Dq agonist with >10 000-fold selectivity for hM3Dq over hM3

Biopolymer-Based hydrogels for agriculture applications: Swelling behavior and slow release of agrochemicals

Hydrogels are cross-linked polymers that can absorb and hold largeamounts of water and aqueous solutions due to the presence of hydrophilic functional groups in their 3D network. These materials also serve as vehicles of different active compounds because they can regulate their release rate. Because of such properties, hydrogels are currently used in many areas including agriculture, mainly as water retention agents for soil conditioning, and as carriers of agrochemicals for their slow or sustained-release. However, most of the hydrogels currently available on the market are based on polyacrylamide and acrylate derivatives, which means that they are not completely biodegradable, i.e. are considered as potential soil contaminants and present certain degree of toxicity. In this context, the development of biodegradable hydrogels for their use in agriculture is gaining interest worldwide. Biopolymers such as chitosan, cellulose, alginate and their derivatives are being explored due to their biocompatibility, biodegradability and low cost. Briefly, in this chapter, recent studies on biopolymer-based hydrogels for their use in agriculture are discussed in terms of their synthesis, swelling behavior, as well as their uses for slow and controlled release of agrochemicals.Fil: Tomadoni, Bárbara María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; ArgentinaFil: Casalongue, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Biológicas. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Biológicas; ArgentinaFil: Alvarez, Vera Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Ciencia y Tecnología de Materiales. Universidad Nacional de Mar del Plata. Facultad de Ingeniería. Instituto de Investigaciones en Ciencia y Tecnología de Materiales; Argentin