Joseph Benjamin Rucker
Integral Molecular
Project start date: 2011-02-01
Project end date: 2013-01-31
Sponsored Links Excellgen http://Excellgen.com
Grants awarded to Joseph Benjamin Rucker
DEVELOPMENT OF TASTE RECEPTOR LIGANDS USING STRUCTURE-ACTIVITY STUDIES
Joseph Benjamin Rucker, Director, R & D
Integral Molecular, 3701 Market St, 4th Floor, Philadelphia, Pa 19104-5502
Grant 5R43DC010105-02 from National Institute On Deafness And Other Communication Disorders
Abstract: As the primary mechanism by which animals detect nutrient-rich foods and discriminate against toxins, the sense of taste has a significant impact on health and behavior. Bitter tastes are perceived with high sensitivity and broad specificity, and can evoke strong aversive reactions that influence health-related behaviors such as dietary preference and pharmaceutical compliance. Conversely, sweet taste facilitates the detection and consumption of high carbohydrate (and hence highly caloric) foods, but over-consumption of calories can lead to obesity and diabetes. It is therefore desirable in many circumstances to manipulate taste perception and/or to provide taste substitutes. Bitter, sweet, and umami (savory) tastes are detected at the cellular level by a family of taste receptors (TASRs), which belong to the G protein-coupled receptor (GPCR) superfamily of proteins. Because they are refractory to direct structural visualization such as x-ray crystallography, very little is known about the structural features of TASRs that are responsible for binding ligands. Elucidating TASR-ligand structural interactions could enable the development of health-related products, such as bitter blockers and sugar substitutes. The results of this proposal would enable ligands of TASRs, and possibly other GPCRs, to be developed. Taste ligands are currently used to mask aversive tastes, improve patient compliance, influence choice of foods, and modify caloric intake, so routinely influence daily human activity. This proposal will contribute to human health by using a research platform to discover novel taste ligands
Keywords: Abbreviations; Amino Acids; Animals; Assay; Behavior; Binding; Binding (Molecular Function); Binding Sites; Bioassay; Biologic Assays; Biological Assay; Caloric Intake; Calories; Carbohydrates; Cell Communication and Signaling; Cell Signaling; Chemical Structure; Combining Site; Compliance behavior; Computer Simulation; Computerized Models; Consumption; Crystallographies; Crystallography; Data; Detection; Development; Diabetes Mellitus; Energy Intake; Evaluation; Family; Flavoring; Flavoring Agents; Food; G Protein-Complex Receptor; G-Protein-Coupled Receptors; Genetics-Mutagenesis; Goals; Gustation; Health; Health behavior; Human; Human Activities; Human, General; Imagery; Intracellular Communication and Signaling; Lead; Libraries; Ligand Binding; Ligands; Man (Taxonomy); Man, Modern; Maps; Masks; Mathematical Model Simulation; Mathematical Models and Simulations; Mediating; Methods; Modeling; Models, Computer; Molecular Biology, Mutagenesis; Molecular Interaction; Mutagenesis; Nutrient; Obesity; Patient Compliance; Patient Cooperation; Pb element; Pharmaceutical Agent; Pharmaceuticals; Pharmacologic Substance; Pharmacological Substance; Phase; Proteins; Reaction; Reactive Site; Receptor Protein; Refractory; Research; Savory; Screening procedure; Shotguns; Signal Transduction; Signal Transduction Systems; Signaling; Simulation, Computer based; Specificity; Structural Models; Structure; Structure-Activity Relationship; Sugar Substitute; Sweeteners; Sweetening Agents; Taste; Taste Perception; Testing; Toxin; Treatment Compliance; Visualization; adiposity; aminoacid; base; biological signal transduction; caloric dietary content; calorie (nutrition); chemical structure function; compliance cooperation; computational modeling; computational models; computational simulation; computer based models; computerized modeling; computerized simulation; corpulence; corpulency; corpulentia; design; designing; diabetes; gene product; heavy metal Pb; heavy metal lead; improved; in silico; mutant; novel; obese; obese people; obese person; obese population; patient adherence; phase 1 study; preference; public health relevance; receptor; salicin; salicyl alcohol glucoside; screening; screenings; structure function relationship; sweet taste; sweet taste perception; therapy compliance; therapy cooperation; tool; virtual simulation
Relevance: Taste ligands are currently used to mask aversive tastes, improve patient compliance, influence choice of foods, and modify caloric intake, so routinely influence daily human activity. This proposal will contribute to human health by using a research platform to discover novel taste ligands
Project start date: 2009-07-01
Project end date: 2011-06-30
Budget start date: 1-JUL-2010
Budget end date: 30-JUN-2011
PFA/PA: PA-08-071
5R43DC010105-02 (2010): $373651
1R43DC010105-01 (2009): $322592