Receptor space

The switching efficiency of lumophore-spacer-receptor systems can be improved by using multiple receptor modules. The PET rate is increased in the device when free of guest ions since more than one site can provide the transiting electron. The simplest cases, such as 4, are those where the receptor units are well separated to prevent interdependent ion binding with an interposed lumophore to minimize the lumophore-receptor spacing for maximum PET rates. Besides this statistical effect, receptors may also cooperatively participate in PET. This may be the case in 5 and 6. ... 

Dlhydrofplate Reductase Inhibitors - This enzyme (DHFF) reduces dlhydrofollc acid (] ) to tetrahydrofollc acid - an essential cofactor with important roles In DNA synthesis and cell growth. DHFR can be widely different In structure in different cells, and Inhibitors which exploit these differences Include clinically useful antibacterial, antiprotozoal, Immunosuppressant and antlneoplastlc drugs. A vast amount of synthetic analog work in this field has been done, much of it by Baker.68 Hansch and co-workers used data from several groups and QSAR techniques to "map" receptor space for DHFR from rat liver, from... 

Figure 16.5 Distribution of a set of 2929 nuclear receptor bioactive ligands (white circles) and 135 nuclear receptor drugs (black squares) inthe plane defined by the molecularweight (MW) and clogP descriptors. The dashed region defines the nuclear receptor space.

Once the molecules are aligned, a grid or lattice is established which surrounds the set of analogs in potential receptor space although 0.2 nm (= 2 A) is the default value for the distance between the grid points, other values may be chosen smaller distances seem desirable, but they lead to unreasonably large numbers of grid points. 

During the optimization process, the vertices of H are assigned to the receptor cavity, to the receptor walls or to the exterior of cavity that is the so-called steric irrelevant zone. The degree of steric misfit for the molecule Mj, i.e. the value of MTDi, is defined as the sum of the number of cavity vertices in H unoccupied by Mi and the number of waU vertices in H occupied by Mi. The whole number of H (meaning cavity, wall and irrelevant zraie) obtained by the optimization procedure makes up a hypothetical steric receptor map. Really, the optimization procedure is a mapping of a receptor space by means of regression analysis (Simon et al. 1978,1984 Ciubotariu et al. 2001a, b). 

At the level of the chemoreceptor, differences in stimulus intensity result in differences in the rate of impulses transmitted to the central nervous system. As an insect moves in space or remains in one place, this information alone can potentially provide for a temporal comparison, and thus an interpretation of the stimulus pattern that is changing in its vicinity or that it is passing through. If an insect has a multiple receptor system with receptors spaced at sufficient distances to perceive a detectable difference in stimulus intensities, an instantaneous comparison can be made to interpret the nature of the stimulus pattern at one point in time. As summarized by Stadler, Chapter 1 and Mustaparta, Chapter 2, nothing is known as yet about the neural mechanisms responsible for integration through temporal and instantaneous comparisons. 

A persistent idea is that there is a very small number of flavor quaUties or characteristics, called primaries, each detected by a different kind of receptor site in the sensory organ. It is thought that each of these primary sites can be excited independently but that some chemicals can react with more than one site producing the perception of several flavor quaUties simultaneously (12). Sweet, sour, salty, bitter, and umami quaUties are generally accepted as five of the primaries for taste sucrose, hydrochloric acid, sodium chloride, quinine, and glutamate, respectively, are compounds that have these primary tastes. Sucrose is only sweet, quinine is only bitter, etc saccharin, however, is slightly bitter as well as sweet and its Stevens law exponent is 0.8, between that for purely sweet (1.5) and purely bitter (0.6) compounds (34). There is evidence that all compounds with the same primary taste characteristic have the same psychophysical exponent even though they may have different threshold values (24). The flavor of a complex food can be described as a combination of a smaller number of flavor primaries, each with an associated intensity. A flavor may be described as a vector in which the primaries make up the coordinates of the flavor space. 

The retinoid X receptor forms heterodimers that recognize tandem repeats with variable spacings... 

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