Functional odor classification through a medicinal chemistry approach

Crucial for any hypothesis about odor coding is the classification and prediction of sensory qualities in chemical compounds. The relationship between perceptual quality and molecular structure has occupied olfactory scientists throughout the 20th century, but details of the mechanism remain elusive. Odor molecules are typically organic compounds of low molecular weight that may be aliphatic or aromatic, may be saturated or unsaturated, and may have diverse functional polar groups. However, many molecules conforming to these characteristics are odorless. One approach recently used to solve this problem was to apply machine learning strategies to a large set of odors and human classifiers in an attempt to find common and unique chemical features that would predict a chemical’s odor. We use an alternative method that relies more on the biological responses of olfactory sensory neurons and then applies the principles of medicinal chemistry, a technique widely used in drug discovery. We demonstrate the effectiveness of this strategy through a classification for esters, an important odorant for the creation of flavor in wine. Our findings indicate that computational approaches that do not account for biological responses will be plagued by both false positives and false negatives and fail to provide meaningful mechanistic data. However, the two approaches used in tandem could resolve many of the paradoxes in odor perception

Applying medicinal chemistry strategies to understand odorant discrimination

Associating an odorant’s chemical structure with its percept is a long-standing challenge. One hindrance may come from the adoption of the organic chemistry scheme of molecular description and classification. Chemists classify molecules according to characteristics that are useful in synthesis or isolation, but which may be of little importance to a biological sensory system. Accordingly, we look to medicinal chemistry, which emphasizes biological function over chemical form, in an attempt to discern which among the many molecular features are most important for odour discrimination. Here we use medicinal chemistry concepts to assemble a panel of molecules to test how heteroaromatic ring substitution of the benzene ring will change the odour percept of acetophenone. This work allows us to describe an extensive rule in odorant detection by mammalian olfactory receptors. Whereas organic chemistry would have predicted the ring size and composition to be key features, our work reveals that the topological polar surface area is the key feature for the discrimination of these odorants

Amphiphilic diblock copolymers with adhesive properties: I. Structure and swelling with water

We study asymmetric block copolymers with the simple diblock AB architecture, in the case where the longer block A is both hydrophobic and "soft", whereas the shorter block B is hydrophilic and "hard". Materials with such a particular combination of physico-chemical and mechanical properties have distinctive advantages, in particular for designing water-compatible adhesive materials. The phase diagram is established, combining NMR and SAXS characterisations of the materials. The swelling with water is monitored through gravimetry and "time-resolved" SAXS. Indications of maintained adhesive properties in a wet environment are given

Candidate chemosensory genes in the stemborer Sesamia nonagrioides

The stemborer Sesamia nonagrioides is an important pest of maize in the Mediterranean Basin. Like other moths, this noctuid uses its chemosensory system to efficiently interact with its environment. However, very little is known on the molecular mechanisms that underlie chemosensation in this species. Here, we used next-generation sequencing (454 and Illumina) on different tissues from adult and larvae, including chemosensory organs and female ovipositors, to describe the chemosensory transcriptome of S. nonagrioides and identify key molecular components of the pheromone production and detection systems. We identified a total of 68 candidate chemosensory genes in this species, including 31 candidate binding-proteins and 23 chemosensory receptors. In particular, we retrieved the three co-receptors Orco, IR25a and IR8a necessary for chemosensory receptor functioning. Focusing on the pheromonal communication system, we identified a new pheromone-binding protein in this species, four candidate pheromone receptors and 12 carboxylesterases as candidate acetate degrading enzymes. In addition, we identified enzymes putatively involved in S. nonagrioides pheromone biosynthesis, including a Delta 11-desaturase and different acetyltransferases and reductases. RNAseq analyses and RT-PCR were combined to profile gene expression in different tissues. This study constitutes the first large scale description of chemosensory genes in S. nonagrioides

Interfacial Adhesion of Fully Transient, Mussel‐Inspired Hydrogels with Different Network Crosslink Modalities

In fully transient, mussel-inspired hydrogels, metal-coordinate complexes form supramolecular crosslinks, which offer tunable viscoelastic properties and mechanical reversibility. The metal-coordination complexation that comprises the crosslinks can take on tris-, bis-, mono-, and free-state modalities (3, 2, 1, or 0 ligands per ion, respectively). Although prior work has established relationships between network crosslinking and mechanical properties, the effect of crosslink and ligand modalities on gel-surface adhesion is not well understood for fully transient hydrogels. Using glass and nickel-coated spherical probes, the effect of network crosslinking modalities on the adhesive strength of hydrogels based on histidine-Ni2+ and nitrodopamine-Fe3+ ion crosslinks is investigated. Since crosslink modalities have a strong impact on the mechanical properties of the bulk network, it is first determined how adhesion relates to the mechanical properties, regardless of the distribution of crosslinking modalities and ligand type. It is ultimately found that the peak adhesive stress increases with decreasing percentage of ligands in tris-crosslinks