Isosteric effects

Here we intend to consider only the regulation of the enzyme protein in detail, and, in so doing, we must distinguish between isosteric and allosteric effects. Isosteric effects are already familiar to us. Particular substances which resemble structurally the normal substrates are bound to the same site as the normal substrates (Fig. 154). Since they are bound to the same site they are called "isosteric. However, inspite of their similarity... 

Isosteric effects are caused by the direct interaction between two substrate or inhibitor molecules or enzyme regions allosteric effects are related to the mutual influence of spatially separated enzymatic sites localized on different subunits. 

From the above argument and Eq. (16) we instantaneously find that the isosteric heat of adsorption cannot be constant within the two-phase region but must also show changes with the surface coverage. In the case of heat capacity we also observe important effects due to the surface heterogeneity. 

The enthalpies of reaction for nucleophilic carbencs depend on the stereoelec-tronic properties of the ligands affecting the availability of the carbene lone pair. An example of electronic influence is the 3.5 kcal/mol enthalpy difference between the isosteric pair IMes and IMesCI that shows the electron-withdrawing nature of Cl compared to H. This trend again is in line with electron donor/withdrawing ability of arene substituents. The effect in this la.st case is a long range electronic... 

Benzacridine tetrahydroepoxides and did epoxides. The isosteric molecules BA, benz[a]acridine (BaAcr) and benz[c]acridine (BcAcr) and their derivatives provide excellent probes for studying the effect of electronic changes upon biological properties. The... 

M. Clare, R. A. Mueller, and K. Houseman, Effect of hydroxyl group configuration in hydroxyethlamine dipeptide isosteres on HIV protease inhibition, J. Med. Chem. 34 1222(1991). 

Once again, clinical studies reveal a divergence between potency and qualitative effect. No in vitro or animal model studies have yet indicated any major difference between oxygen at the 4-position and its sulfur isostere, although there are changes in their experimentally measured ionization potentials (54). 

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