Receptor-specific interaction

FIGURE 2.2 Most drugs form a reversible complex with their specific receptors. 

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He, B., Minges, J.T., Lee, L.W. and Wilson, E.M. (2002) The FXXLF motif mediates androgen receptor-specific interactions with coregulators. The Journal of Biological Chemistry, 277, 10226-10235. 

For a putative drug molecule to compete effectively with the natural substrate at a given receptor, specific interactions with protein atoms in the receptor site must take place. These usually take the form of noncovalent interactions, the sura of which should be favorable enough to overcome the penalty incurred by steric repulsions, the freezing of transladonal and rotational degrees of freedom, desolvation, and other forces that would otherwise prevent binding. ... 

The interest in vesicles as models for cell biomembranes has led to much work on the interactions within and between lipid layers. The primary contributions to vesicle stability and curvature include those familiar to us already, the electrostatic interactions between charged head groups (Chapter V) and the van der Waals interaction between layers (Chapter VI). An additional force due to thermal fluctuations in membranes produces a steric repulsion between membranes known as the Helfrich or undulation interaction. This force has been quantified by Sackmann and co-workers using reflection interference contrast microscopy to monitor vesicles weakly adhering to a solid substrate [78]. Membrane fluctuation forces may influence the interactions between proteins embedded in them [79]. Finally, in balance with these forces, bending elasticity helps determine shape transitions [80], interactions between inclusions [81], aggregation of membrane junctions [82], and unbinding of pinched membranes [83]. Specific interactions between membrane embedded receptors add an additional complication to biomembrane behavior. These have been stud-... 

Figure 10.11 Sequence-specific interactions between DNA (yellow) and the recognition helix (red) of the glucocorticoid receptor. Three residues, Lys 461, Val 462 and Arg 466 make specific contacts with the edges of the bases In the major groove.

Figure 13.23 The F-G loop in the C-terminal domain of the prolactin receptor is involved in a unique interaction, (a) The F-G loop of the growth hormone receptor (blue) is not involved in any specific interactions with the growth hormone (red), (b) The F-G loop in the prolactin receptor forms a strong zinc-binding site that links the receptor (green) to the hormone (red). (Adapted from W. Somers et at.. Nature 372 478-481, 1994.)...

The label-free detection of biomolecules is another promising field of application for SERS spectroscopy. Tiniest amounts of these molecules can be adsorbed by specific interactions with receptors immobilized on SERS-active surfaces. They can then be identified by their spectra, or specific interactions can be distinguished from unspecific interactions by monitoring characteristic changes in the conformation sensitive SERS spectra of the receptors. 

From these preliminary results, we can assume that such enantiophore queries could be used to search in a database of compounds with unknown enantioselectiv-ities. With respect to the percentage of resolved samples that are retrieved in CHIRBASE, the resulting list should contain a similar yield of compounds providing favorable specific interactions with the CSP receptor binding sites. 

We have seen here that these simple methods which only rely upon the optimal use of molecular graphics tools can address highly specific receptor-ligand interactions. 

In the absence of specific interactions of the receptor - ligand type the change in the Helmholtz free energy (AFadj due to the process of adsorption is AFads = yps - ypi - Ysi, where Yps, YPi and ys, are the protein-solid, protein-liquid and solid-liquid interfacial tensions, respectively [5], It is apparent from this equation that the free energy of adsorption of a protein onto a surface should depend not only of the surface tension of the adhering protein molecules and the substrate material but also on the surface tension of the suspending liquid. Two different situations are possible. 

The process of activation of neutrophils is essentially similar. They are activated, via specific receptors, by interaction with bacteria, binding of chemotactic factors, or antibody-antigen complexes. The resultant rise in intracellular Ca affects many processes in neutrophils, such as assembly of micrombules and the actin-myosin system. These processes are respectively involved in secretion of contents of granules and in motility, which enables neutrophils to seek out the invaders. The activated neutrophils are now ready to destroy the invaders by mechanisms that include production of active derivatives of oxygen. 

Schols D, Baba M, Pauwels R, Desmyter J, De Clercq E. Specific interaction of aurintricarboxylic acid with the human immunodeficiency virus/CD4 cell receptor. Proc Natl Acad Sci USA 1989 86 3322-3326. 

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