Biosensors Involved in Drug Discovery - Biosensors and Biosensor Kinetics - page 64

insights into enhancing the different biosensor performance parameters. The fractal approach
is a convenient means (since it is a lumped parameter) to make the degree of heterogeneity
that exists on the surface more quantitative. Thus, there is some arbitrariness in the fractal
approach. The fractal approach provides additional information about interactions that may
not be obtained by a conventional analysis of biosensor data. In this chapter as mentioned
above, the authors are attempting to relate the fractal dimension, D f , or the degree of hetero-
geneity on the biosensor surface to the different biosensor performance parameters. More
specifically, the authors are interested in finding out how changes in the fractal dimension
or the degree of heterogeneity on the biosensor chip surface affect the different biosensor
parameters of interest.
Unless specifically mentioned there is no nonselective adsorption of the analyte. In other
words, nonspecific binding is ignored. Nonselective adsorption would skew the results
obtained very significantly. In these types of systems, it is imperative to minimize this non-
selective adsorption. The authors also recognize that, in some cases, this nonselective adsorp-
tion may not be a significant component of the adsorbed material and that the rate of
association, which is of a temporal nature would depend on surface availability.
Viht et al. (2007) point out that protein kinases play a significant role in the regulation of pro-
tein function in living cells. In fact, they report that more than 400 human diseases (including
some forms of cancer) may be linked to incorrect protein kinase signaling. According to
Cohen (2002) and Fischer (2004) , protein kinases are the second largest drug targets after
G-protein-coupled receptors. In fact, the protein kinases are the fastest growing category of
drugs in development ( Viht et al., 2007 ). Viht et al. (2007) further report that protein kinases
follow a ternary complex mechanism wherein there is direct transfer of the phosphoryl group
from the ATP to the protein substrate at the active site ( Adams, 2001 ).
Viht et al. (2007) thus assert that three different types of inhibitors that target the active site
are under development. Furthermore, new assays are under development for the evaluation of
these protein kinase inhibitors. For example, these authors suggest that kinase inhibitors may
be detected by the measurement of the binding potency of these compounds to kinase.
Viht et al. (2007) assert that SPR based biosensors have been used for a variety of biomolec-
ular interactions ( Karlsson, 2004; Boozer et al., 2006 ). Inhibitors of protein kinases have also
been characterized by SPR biosensors. Viht et al. (2007) have used the SPR biosensor to help
characterize the interactions between ARC and a isoforms of the catalytic subunit (Ca) of
CAPK. These authors emphasize that the high affinity of the surface-immobilized ARC
toward CAPK C a permits the affinity determination of the binding of the active site of the
kinase.
Viht et al. (2007) report that it is possible to attach ARC-type inhibitors to a polymer matrix
using a suitable tether. This tether is connected to the C terminus of the peptide moiety of the