Applications of fluorescence and bioluminescence resonance energy transfer to drug discovery at G protein coupled receptors

The role of G protein coupled receptors (GPCRs) in numerous physiological processes that may be disrupted or modified in disease makes them key targets for the development of new therapeutic medicines. A wide variety of resonance energy transfer (RET) techniques such as fluorescence RET and bioluminescence RET have been developed in recent years to detect protein–protein interactions in living cells. Furthermore, these techniques are now being exploited to screen for novel compounds that activate or block GPCRs and to search for new, previously undiscovered signaling pathways activated by well-known pharmacologically classified drugs. The high resolution that can be achieved with these RET methods means that they are well suited to study both intramolecular conformational changes in response to ligand binding at the receptor level and intermolecular interactions involving protein translocation in subcellular compartments resulting from external stimuli. In this review we highlight the latest advances in these technologies to illustrate general principles

Big Signals from Small Particles: Regulation of Cell Signaling Pathways by Nanoparticles

"Nanoscience" is recognized as an emerging science of objects that have at least one dimension ranging from a few nanometers to less than 100 nm. Through the manipulation of organic and inorganic materials at the atomic level, novel materials can be prepared with different thermal, optical, electrical, and mechanical properties, compared to the bulk state of the same materials. Nanoscale entities are abundant in biological systems and include diverse entities such as proteins, small-molecule drugs, metabolites, viruses, and antibodies. In the past 20 years, there has been a rapid expansion in the number of engineered nanosystems that have been developed for biological and medical applications. Nanotechnology is a demanding new field based on the convergence of technical disciplines such as physics, chemistry, engineering and computer sciences, cell biology, and neuroscience. Nanotechnology is recognized as the design, preparation, characterization, and applications of materials, where at least one dimension is on the nanometer scale. Engineered nanodevices are finding an ever-expanding range of applications by versatile modifications of their properties. These involve modifications of the shape, size, surface, and chemical properties. For instance, the surface of nanomaterials can be tailored to a desired use, e.g., to improve the biocompatibility of implantable materials or through the attachment of receptors for targeted analyte binding or enhanced adhesion to biological structures.Deposited by bulk impor