Microbial Enzymes and Biotransformations Microbial Enzymes and ...

48 Setford and Newman
Fig. 8. Schematic of split-and-mix combinatorial synthesis.
3.2.2. Combinatorial Chemistry and Solid-Phase Organic Synthesis
Combinatorial chemistry and solid-phase organic synthesis techniques can
be used to prepare libraries for the screening of novel affinity ligands for sensor
applications. Current approaches involve the use of peptide libraries using
natural and unnatural amino acids as building blocks. Various types of resins,
such as Merrifield, Wang, Trityl, and PEGA, are used to prepare libraries using
split-and-mix synthesis (Fig. 8). The libraries are screened and tethered onto the
resin beads, and the positive results can be visualized under a microscope.
When libraries are screened in solution, techniques such as surface plasmon
resonance (SPR) can be used to measure the binding. Potentially useful ligands
can then be structurally analyzed and subsequently resynthesized on a large
scale for evaluation and kinetics study.
The use of combinatorial methods for the production of receptors for biosensors
is still in its infancy. However, the technique is very widely used in drug discovery
by the major pharmaceutical companies. The level of commitment to this
technology for pharmaceutical applications means that advances in understanding
and equipment will have natural spin-off benefits for analytical applications.
However, the investments in terms of time, equipment, and personnel to obtain
a ligand with the desired characteristics are not cheap and this may make the
technology applicable only to biosensors with considerable market value.
Most importantly, biomimetics of all types have the potential to overcome
some of the shortfalls associated with biological components, primarily poor