Conclusions and Future Prospects

Success in biotechnology and biochemistry is well attributed to developments in analytical techniques and instrumentation. The production of several high value therapeutics would not have gone to completion if it were not for efficient methods in protein purification. Conventional purification techniques are becoming outdated for industrial applications, and technologies based on proteins, peptides and oligonucleotides have gained an impetus, although they are prone to enzymatic and chemical degradation and have short in vivo and in vitro lifetimes. Peptides and oligonucleotides make undesirable drug candidates owing to poor oral activities. Furthermore, peptides have a large number of conformations that may be highly flexible and which can make attainment of the most favourable conformation and orientation difficult and lead to low affinity ligand-protein complexes.

The current focus is on compounds that lack the repetitive backbone units linked by facile bonds prone to chemical and biological (proteases and nu-cleases) cleavage. Thus, large number of alternative methodologies have been proposed to replace the peptide bond (peptidomimetics) with the use of pep-toids, carbamates, sulfones, alkenes, urea, phos-phodiesters and sulfonamides.

Sophisticated organic synthesis has inspired chemists to synthesize receptors, drugs, peptides, nucleo-

tides and their mimetics to identify epitopes on surfaces of proteins for therapeutic, diagnostic, inhibitory and purification purposes. A combinatorial approach has become the choice of several chemists to maximize the possibility of success for lead generation, optimization and development of candidate drugs or ligands. However, it is very expensive and laborious to produce, screen and manage data for all these compounds. Some direction and rationale is essential. Information about structure-activity relationship lends that extra information that can help in pre-selection.

The availability of fast and sophisticated computer modelling software packages and the marriage of rationale and serendipity makes the design and synthesis a successful venture for investigation. A prerequisite in de novo design of biomimetics ligands is the availability of protein structural data and information on protein-ligand complexes. With the advances in proteomics, protein structural availability is hardly a limiting issue. In the coming years, there will be an explosion of protein structural data. The completion of the Human Genome Project will unveil countless new proteins, challenging methodologies such as random screening, rational design, combinatorial chemistry and high-throughput screening to become rapid, inexpensive and fully automated with the incorporation of robotics. Simultaneous developments in data management, proteomics and bioinfor-matics will integrate the technology and reduce time, cost and labour. The challenge to mimic the action of natural biological recognition is ongoing, and, as nature uses only a repertoire of 20 amino acids to generate an endless combinatorial list of proteins, the challenge for rational ligand design continues.

See Colour Plates 15, 16, 17,18.

See also: II/Affinity Separation: Affinity Membranes; Biochemical Engineering Aspects; Covalent Chromatography; Dye Ligands; Imprint Polymers; Theory and Development of Affinity Chromatography. Appendix 2/Essential Guides to Method Development in Affinity Chromatography.

Solar Panel Basics

Solar Panel Basics

Global warming is a huge problem which will significantly affect every country in the world. Many people all over the world are trying to do whatever they can to help combat the effects of global warming. One of the ways that people can fight global warming is to reduce their dependence on non-renewable energy sources like oil and petroleum based products.

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