Backbone variations

The models of the renin structure indicated that the P2 subsite was narrow at the backbone region, so disubstitution of the P2 a-carbon was not recommended. Subsequent experimental evidence confirmed this prediction. In one particular series, where epimerization of the aminomalonate at the P2 site of inhibitor 4 (Table 1) was a concern [27], the a-methyl deriv- 

5 Structure-Based Design From Renin to HIV-1 Protease 

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A number of experiments have been conducted to establish various aspects of structure-activity relationships (SAR) of substrates. Although the greatest emphasis has been upon the nature and orientation of the side chains on the glycerol backbone, variations in the phosphate headgroup have also been explored. 

One additional aspect of studies on the core and backbone variation in... 

The surface activity of organosilicon polymers with backbones other than siloxane is not very well known. Interest in varying the backbone in organosilicon polymers does not normally stem from a desire to modify surface properties. Usually, the purpose of backbone variation is to increase thermal stability, as for example, with poly(silphenylenesiloxane) and poly-(carboranesiloxane) copolymers. Because thermal stability is often achieved by increasing TgS by using rigid backbones, most backbone variations will have a detrimental effect on polymer surface activity. 

Figure 7 Backbone variations of BIBP 3226. The receptor affinity has been determined using human neuroblastoma cells (SK-N-MC), which con-stitutively express the Y1 receptor.

ATM—it is possible to over plasticize an NBR compound with glycol ether esters without exudation appearing. This is detected by a precipitous faUoff in physical properties. The plasticizer has literally solvated the polymer backbone. Variations of this condition can be found in all highly polar polymer systems. 

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