AllChemE Report: "Chemistry - Europe & the Future" - Graphical version

Life processes

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The involvement of chemists at the interfaces with life sciences, in a multidisciplinary collaboration with biologists, clinicians, and agronomists, has resulted in the discovery of new products, including pharmaceuticals and materials for medicine and public health nd new products for agriculture, allowing more efficient and safer food production. Some of the diseases which have historically killed people in high numbers have now been most eradicated, but the fight against diseases must continue. We must also resolve the problems of malnutrition and shortage of food, which continue to be responsible for large number of deaths.

 

Understanding the Chemistry of Life

To understand the chemistry of life processes it is essential to unravel the basic chemical reactions at their heart. During the last few decades this has been greatly facilitated by a knowledge of the molecular structures of important biological molecules like DNA, enzymes, proteins and antibodies. This has been the key to extraordinary progress in modern biology and medicine. This domain of structural biology is a great challenge for the spectroscopic and structural techniques of chemistry. Penetrating it has illuminated and enlightened our understanding of the chemical mechanisms involved in physiological processes, affording us the capability to act on them in order to maintain or correct them, leading to great improvements in healthcare.

Progress in structural biology and biological chemistry necessitates the isolation and purification of the chemical components of living systems and their structural identification by X-ray crystallography, nuclear magnetic resonance spectroscopy (NMR), mass spectrometry and electronic microscopy. These techniques may be backed up by the synchrotron and neutron radiation sources available in Europe's international centre in Grenoble, Institut Laue Langevin (ILL) and European Synchrotron Research Facility (ESRF). The continuing improvement of these physico-chemical techniques makes it possible to study minute quantities of material.

Computer simulation and modelling have become valuable tools in the study of the structural, dynamic and thermodynamic characteristics of complex biochemical systems. These techniques can not only assist in the elucidation of the structure of very complex molecules, but also throw light on how such molecules may fold and unfold in solution. Such techniques also demonstrate how two very large biological molecules recognise each other and adjust their structures as a prelude to carrying out a biological reaction. The 'modelling' programmes are based on methods derived from theoretical chemistry or on empirical model scenarios derived from simple molecules. Such techniques are invaluable in the rational designs of drugs in pharmaceutical chemistry (see later).

Biomimetic chemistry is the field of experimental simulation or modelling of biological systems in which chemists try to mimic the complex systems found in nature using less complicated artificial chemical systems. These studies will greatly assist in the understanding of the chemistry of biological reactions and will lead to the invention of completely new chemical processes and new materials useful in industry and society.

 

Synthesis of New Pharmaceuticals

Many currently used drugs were discovered through the traditional pharmaceutical screening of substances isolated from natural sources. Natural sources, usually plants, marine organisms and micro-organisms, are a fantastic reservoir of molecules, and many of them remain to be screened for their potential pharmaceutical properties. Some substances correspond to chemicals isolated from natural sources used in folk medicine. The activity of these natural compounds can also be improved by chemical modification of the natural structure. It can happen that the natural source of a powerful and effective drug is not able to provide the active component in sufficient quantity to satisfy medical needs. In such a case it is necessary to have recourse to an efficient chemical synthesis. For instance, the chemical compound Taxol is very active against ovarian and breast cancers, but the molecule is isolated only in very small amounts from the bark of Taxus baccata (yew tree). However, the active molecule obtained from the bark is actually an assembly of two components, the main part of which can also be obtained in significant amounts from yew tree pine needles. Combination of this naturally-produced material with the minor component, obtained by direct chemical synthesis, constitutes Taxol virtually identical to that obtained from the bark. During the laboratory synthesis procedure, an intermediate, TaxotereTM, is obtained which is even more active than Taxol itself.

Traditional screening approaches to drug discovery have low success rates (averaging no more than one success in over 20,000 products screened). Combinatorial chemistry has recently revolutionised drug discovery by providing access to a huge number of molecules. This new technique can be applied to small molecules as well as macromolecules such as proteins, nucleotides and carbohydrates. Large numbers of substances can now be screened for a specific drug activity in new automated screening systems that utilise the natural structures which are relevant for diseases. These receptors, enzymes, channels, etc can be obtained in useful quantities using gene technology. Such speed will have considerable impact on the efficiency of drug research and discovery processes.

Molecular modelling and simulation methods, rational design and computational studies of protein-drug interactions (lock-and-key chemistry) permit an insight into how drugs work at the atomic and molecular levels and significantly aid the design of active molecules. The mechanisms which determine the recognition behaviour and operation of drugs towards proteins can be studied in detail, the computer making it possible for the scientists to see what shape and charge distribution the guest molecule should have to fit into the binding niche of the respective protein host. This means that the usual trial-and-error strategy, or random search, can be improved upon by means of computational methods.

Once a molecule is identified as a candidate drug, chemists and chemical engineers have to find the best way to synthesise it. Selective synthesis, which gives only the desired product and avoids the formation of undesirable by-products, is a permanent challenge for chemists. Stereo-selectivity, and in particular asymmetric synthesis, is a key area due to its potential for the production of single enantiomers (mirror image molecules). This is particularly important in the case of bio-active compounds since often only one of the enantiomers shows the desired activity. Two of the major approaches in this area are the use of transition metal catalysts bearing chiral ligands and the application of bio-transformations where enzymes themselves are employed as the enantio-selective catalyst. Use of catalytic antibodies is also a growing area of activity.

Chemists, together with biochemists, have contributed to remarkable advances in many aspects of health and life sciences. The synthesis and industrial production of highly complex molecular structures like steroidal hormones and their analogues to provide contraceptive agents have had an impact not only on medicine but also on society. Chemical synthesis of peptides and small proteins is now a routine automated technique and could provide peptides in useful quantities. Some important physiological peptides for clinical use, for example peptidal hormones, are now produced by such methods. DNA and RNA fragments are now available via automated chemical synthesis. In particular, synthetic oligonucleotides of the 'antisense' type (having the complementary sequence of a genetic message) can bind selectively to the corresponding sequence of DNA or RNA with high specificity. Treatments of some diseases, ranging from virus infections to genetic disorders, now rely upon molecules found by these techniques. Oligosaccharides, which are associated with group blood factors, have applications in blood diagnosis and are made by direct chemical synthesis.

 

Gene Technology and Biotechnology

Gene technology has opened a door to the analysis of genetic information and the introduction of new types of activity into the genetic information of an organism. Chemists, biochemists and molecular biologists are making key contributions to design techniques for analysing, understanding and modifying in a precise way the genetic configuration of living organisms. Genome mapping is also a big challenge for the understanding and treatment of genetic disorders. Sequencing DNA molecules, using the polymerase chain reaction (PCR) to amplify small segments of DNA, modifying abnormal segments, then delivering and inserting these segments into genetic material, has opened the way to future gene therapy. This offers great hope for people suffering from genetically-related diseases. Genetic research will teach us more about hereditary disease and will put pharmaceutical research on a more rational basis. Genetic targeting methods are being developed to address the specific sites of desired interference.

The advances in gene technology have also been very fruitful for biotechnology. Traditional biotechnology, such as the processing of bread, beer or cheese, dates back many thousands of years. The new biotechnology revolution began 25 years ago with the mastering of gene technology.

Modern biotechnology is spreading out into a huge variety of areas. Screening systems based on cloned receptors or reporter genes are used in the search for new drug candidates with increased specificity. Mutated proteins with increased therapeutic values or improved enzymatic properties can be constructed, and rational protein design is becoming increasingly feasible due to new and refined analytical techniques.

The techniques used in modern biotechnology will have increasing effects on many industrial sectors, including pharmaceuticals, environmental technologies, plant breeding, food processing and the textile, paper and pulp and leather industries. The benefits will be felt in agriculture and food production, but above all in improvements in human health. Substances extracted from natural sources may be contaminated by compounds that present a risk to health. Biotechnology may allow us to circumvent the problem. Recombinant DNA technology enables the production of vaccines in newer and safer ways and helps the production of complex protein-containing drugs and enzymes. The production of human growth hormone by genetic engineering affords a product devoid of the prion that is present in its natural source and which may be related to the causes of Creutzfeld-Jacob disease. Numerous other such cases can be found, a particularly important one being that of the production of factor VIII for blood transfusion without risk of infection by HIV.

Modern biotechnology is not the magic bullet which will cure cancer or eliminate hunger in developing countries, but it is a powerful and effective technology which will provide novel ways of tackling unsolved problems (see Caring for our planet).

Biotechnology-based growth in Europe faces a number of factors unique to the structure and operating climate for investment, research and development as well as the availability of skilled labour. Biotechnology, in common with all practical technologies, raises issues of processing and safety and sensible regulations for their control are needed. But, more than any other innovative technology, biotechnology will have a dramatic impact on global economic and competitive conditions.

 

Devices and New Materials for Medicine

An important aspect of the advances in material sciences during the last few decades is the design and synthesis of bio-compatible materials for artificial limbs and medical devices. New alloys, ceramics, composite materials, special structural polymers and plastics are used to replace or repair joints, lenses, teeth, vessels, etc. The performance of surgical prosthetics and implants, particularly for temporary emplacement (which demands bio-compatibility and eventual benign bio-degradation), is being substantially improved by using combinations of biological and synthetic materials, or through chemical modification of biological polymers. The promising performance of perfluorohydrocarbon polymers as oxygen carriers suggests that their temporary use as artificial blood may soon prove possible.

The design of an effective pharmaceutical drug is not just a matter of finding an active molecule. The effectiveness of that drug is dependent on the ability of the active molecule to reach its target in the organism efficiently and selectively. It is therefore necessary to design a protective formulation for the drug which will enable it to cross membranes and protect it from destruction by the metabolism. New drug delivery systems to solve these problems have been designed by chemists and pharmacologists. Microcapsules, microsomes, liposomes, transdermal patches and direct implantation of biodegradable polymers containing the active drug for slow release of the active molecule are some examples.

As a consequence of the progress in analytical instrumentation and techniques developed by chemists and physicians, clinicians have at their disposal powerful methods for medical diagnostics. Non-invasive diagnostic tools include Magnetic Resonance Imaging (MRI), a spin-off of the development of nuclear magnetic resonance used in structural chemistry, Doppler imaging, photon and positron tomography and radioactive techniques. Chemists have contributed to these techniques by designing and developing special chemicals such as contrast agents for MRI and radioisotopes for positron tomography.

The progress made in chemical and biochemical analysis using chromatography and electrophoresis has been very beneficial for medical diagnostics. The development of sensors based on electro-enzymatic processes has provided miniaturised portable blood sugar analysers for diabetics. Such self-diagnosing technology, based on chemistry and biochemistry, will grow dramatically.

 

Agricultural Chemistry

Chemistry has been a major contributor to the development of modern agriculture. The design of biologically active molecules for pesticides and selective herbicides with low toxicity, the production of fertilisers which improve crop quality and yield and the extension of the shelf-life and stability of foods are just a few examples.

The invention and discovery of new chemicals for pesticidal and fungicidal uses is an important contemporary topic. Previous generations of such substances were effective in dealing with the specific pest or fungus, but they were too broad in action and too persistent. New research will lead to substances which are very selective, are active at very low concentration and which after use will be rapidly degraded by soil micro-organisms without harm to humans or the environment.

Of course, nature produces chemicals in great abundance. This is evident, for example, in the production of sugar cane from which carbohydrates (including sucrose) can be extracted. Natural fats and oils (oleochemicals) have high ecological potential as sources of chemicals for detergents, cosmetics, lubricants and bio-degradable polymers. By imaginative development of agriculture, it will be possible to generate sources of chemicals for new medicines, polymers and detergents.