Other Mimetics

A number of peptide mimetics that have been designed wdth the aid of computational chemistry were intended as mimics of secondary structure features. Since mimetics not intended for immediate testing in a specific screen are not covered in this review, the reader is referred to some of these individual studies ° ° as well as the listed reviews - for particular examples. 

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The different membrane-mimetic compartments have been utilized in a large variety of applications. Possible commercial applications of monolayer and multilayer LB films have been surveyed [28]. They, along with other mimetic... 

One frozen dessert is made with Simplesse, a protein-based fat mimetic that contains no fat (37). Other dairy product developments include a fat flavor, produced by encapsulating milk fatty acids in maltodextrins (38) fat-free cottage cheeses and 2% fat milk, prepared by steam stripping cream with partial fat addback, with a cholesterol level about 60% lower than the starting material (39). 

In addition to the sex hormones and corticosteroids, other steroid dmgs have substantial worldwide markets. For example, cytostatic hormones had worldwide sales of approximately 1.8 biUion in 1994. Included in these 1.8 biUion are several steroids or steroid-mimetics such as megestrol acetate and tamoxifen (282), respectively (262). 

Endocrine disruptors apparently affect all nuclear receptors. Thus, a notable increment in impotence, alterations of the libido and of oligospermia in workers exposed to pesticides has been described. These alterations are due to the action of some compounds with estrogen-mimetic action and to their interaction with the androgen receptor. Additionally, alterations of thyroid function have been detected in rats exposed to dioxin and other toxic agents,... 

This, together with the previous demonstration that SNAP-5114 has higher affinity for GAT4 than for the other cloned transporters (44), shows that lipophilic, bulky molecules that do not contain a strict GABA mimetic moiety can be used to distinguish between the different cloned GABA transporters. 

Other potent peptide mimetic NS3 protease inhibitors have been reported that incorporate a serine trap on the C-terminal end of the peptide. Thus, the inhibitory activity of telaprevir (VX-950, 59), (7nM vs. NS3, 300 nM vs. the la replicon) is based on truncation of the polypeptide substrate, maximizing binding by alteration of amino acids at the scissile site, and capping both N- and C-terminal ends, the latter with a known dicarbonyl serine trap. This compound has exhibited impressive antiviral activity in animals, and showed a 4.4 log drop in viral load in genotype 1-infected patients in a Phase lb clinical trial [110]. Telaprevir is expected to enter Phase 3 clinical trials in 2007. Additional bicyclo-proline-based P2 tetrapeptides, represented by analog 60 (Kj = 22 nM), have been explored. Although the compounds are selective inhibitors of NS3, little or no cell-based replicon activity was reported, presumably due to poor cellular permeability [111-114], A diastereomer of telaprevir, has been reported to inhibit the replicon with an EC50 of 0.55 pM [115]. 

Scheme 3.52), whereas the corresponding acetyl-protected donor gave little product under the same reaction conditions [512], Additionally, the trichloroacetimidate method has also been applied to synthesize other natural products, such as bupres-tin A and B [517], macrophylloside D [518] and neomycin mimetics [519]. 

Other than RIF and Taxol, many other commonly used clinical drugs have also been shown to activate PXR. These include peptide-mimetic HIV protease inhibitors [53], the cholesterol-lowering lovastatin and the anti-inflammatory dexamethasone [54]. A more comprehensive analysis of the effect of commonly used clinical drugs on PXR activation has recently been published by Sinz and colleagues [55]. 

HUNTING OR FOLLOWING EACH OTHER ORIGINS OF MIMETIC SKILLS ... 

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