Nonspecific targets

Scheme 1.21. Protein assay operation in the presence of target Streptavidin, the biotin moiety of Fl-B specifically associates with Streptavidin and the fluorescein moiety is buried in the adjacent vacant-binding sites. This makes fluorescein far away from P4 and inefficient FRET between them occurs (A). In the presence of nonspecific target, the strong electrostatic interactions between cationic P4 and negatively charged biotinylated fluorescein (Fl-B) result in efficient FRET from P4 to fluorescein (B)...

Although most anesthetics are achiral or are adininistered as racemic mixture, the anesthetic actions are stereoselective. This property can define a specific, rather than a nonspecific, site of action. Stereoselectivity is observed for such barbiturates as thiopental, pentobarbital, and secobarbital. The (3)-enantiomer is modestly more potent (56,57). Additionally, the volatile anesthetic isoflurane also shows stereoselectivity. The (3)-enantiomer is the more active (58). Further evidence that proteins might serve as appropriate targets for general anesthetics come from observations that anesthetics inhibit the activity of the enzyme luciferase. The potencies parallel the anesthetic activities closely (59,60). 

Target protein may have been proreolyzed Nonspecific interaction... 

Note that if Ko values are above 1, there must be a nonspecific interaction between the target molecule and the matrix. In the case of Ko values below 0, the column packing is probably damaged. 

The concept of drug development is based on the findings that retinoid receptors (RARs and RXRs) offer a new approach by targeting different genes depending on the activated retinoid receptor complexes. The multiplicity of these retinoid signaling pathways affords potential for therapeutic opportunity as well as retinoid therapy associated undesired side effects. It is possible that the indiscriminate activation of all pathways by nonspecific retinoid ligands could lead to unacceptable side effects so that any enhanced efficacy would be obtained at the cost of enhanced toxicity. 

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