Target hopping

Target Hopping, Cross Reactivity, Selectivity, Opportunity Mining... 

Figure 5. An example of intra-family target hopping within kinases. According to SiteSorter, Braf kinase, the primary target for the clinical compound BAY 43-9006, is one of the 10 most similar kinases to c-Kit, which has also been shown to bind BAY 43-9006 with sub-micromolar affinity (60% of the binding site residues are consen/ed and colored blue non-consen/ed positions are colored yellow). This cross-reactivity cannot be predicted based on the sequence similarity of the Braf and c-Kit kinase domains, since approximately one-sixth of the human kinome is more sequence similar to Braf than c-KiL...

Figure 6. An example of inter-family target hopping between human and viral aspartyl proteases. The aspartyl protease active site is located at a homodimer interface in HIV and within a single domain in Cathepsin D, so sequence and structure alignments between these proteins cannot be constructed. By using an approach independent of sequence or structure homology to directly align the sites, SiteSorter finds that the HIV protease and Cathepsin D substrate sites are highly similar (identical chemical groups within 1 A are colored dark blue). It has been verified experimentally that Cathepsin D is susceptible to inhibition by HIV-protease inhibitors. ...

Molecular parasites may also have originated in an RNA world. With the appearance of the first inefficient self-replicators, transposition could have been a potentially important alternative to replication as a strategy for successful reproduction and survival. Early parasitic RNAs would simply hop into a self-replicating molecule via catalyzed transesterification, then passively undergo replication. Natural selection would have driven transposition to become site-specific, targeting sequences that did not interfere with the catalytic activities of the... 

Modified TiC>2 surfaces have also found application in the design of fast elec-trochromic devices. The influence of the substrate on the behavior of interfacial assemblies is well illustrated in this book. However, it is important to realize that the electrochromic behavior observed for modified TiC>2 surfaces was not expected. The oxidation and reduction of attached electrochromic dyes are not mediated by the semiconductor itself but by an electron-hopping process, not unlike that observed for redox polymers, where the electrochemical reaction is controlled by the underlying indium-tin oxide (ITO) contact. These developments show that devices based on interfacial assemblies are a realistic target and that further work in this area is worthwhile. 

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