Biological receptors interactions

Figure 9.17 Imagine that a left hand interacts with a chiral object, much as a biological receptor interacts with a chiral molecule, (a) One enantiomer fits into the hand perfectly green thumb, red palm, and gray pinkie finger, with the blue substituent exposed. (b The other enantiomer, however, can t fit into the hand. When the green thumb and gray pinkie finger interact appropriately, the palm holds a blue substituent rather than a red one, with the red substituent exposed.

The information contained in the chemical stmcture of a given ligand is without value unless decoded and executed by the appropriate receptor. The pharmacologic analysis of dmg—receptor interactions is based on the understanding of how the dmg is recognized by the receptor, how the dmg—receptor complex forms, and how the dmg—receptor complex initiates its biological action (12). 

The sensation of sweetness obviously involves interaction between the sweetener and some sort of biological receptor. It might be expected, therefore, that sweeteners share common structural features. Is this the case ... 

Among the difficult (and sometimes referred to as sensitive ) chromatographic separations, those of enantiomeric antipodes and racemic mixtures are of particularly great importance and of the highest interest. This is because many compounds with a therapeutic effect (and incomparably more often the synthetic species than the natural ones) appear in a clearly defined enantiomeric form and for reasons of safety, need to be isolated from their opposite counterparts. Most phar-macodynamically active compounds are equipped with polar functionalities that make them interact with biological receptors and with the other constituents of a biological environment, and it often happens that these functionahties are of the AB type. In such cases, it can be justly concluded that an almost proverbial difficulty... 

For a detailed description of spectral map analysis (SMA), the reader is referred to Section 31.3.5. The method has been designed specifically for the study of drug-receptor interactions [37,44]. The interpretation of the resulting spectral map is different from that of the usual principal components biplot. The former is symmetric with respect to rows and columns, while the latter is not. In particular, the spectral map displays interactions between compounds and receptors. It shows which compounds are most specific for which receptors (or tests) and vice versa. This property will be illustrated by means of an analysis of data reporting on the binding affinities of various opioid analgesics to various opioid receptors [45,46]. In contrast with the previous approach, this application is not based on extra-thermodynamic properties, but is derived entirely from biological activity spectra. 

First described in 1926 by Perrin [16], the theory was greatly expanded by Weber [17], who developed the first instrumentation for the measurement of FP. Dandliker [18] expanded FP into biological systems such as antigen-antibody reactions and hormone-receptor interactions. Jolley [19] developed FP into a commercial system for monitoring of therapeutic drug levels and the detection of drugs of abuse in human body fluids. 

Like FRET, today BRET is predominantly used in biological sciences, especially in the monitoring of protein-protein interactions such as hormone-receptor interaction [223, 224] and protein-DNA interaction in living systems. However, BL resonance energy transfer can also be applied in immunoassays by using for instance a peptide-tagged luciferase and a fluorescein-labeled antipeptide antibody [225]. The development of more BRET assays for small-molecule analytes is thus awaited. 

---