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European Pharmaceutical Contractor
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Previously, reactions such as this were performed in solution and extracting the desired product from a complex mixture of reagents and by-products was by no means a trivial task. The solid phase approach made the production process a relatively routine exercise and so a great many laboratories were able to undertake peptide synthesis themselves. The operations were automated very quickly, although in those early pioneering days, the controlling devices were often crude clockwork systems. This approach was so versatile that the concept was quickly applied to the synthesis of other oligomeric compounds such as nucleotides and carbohydrates. It soon became apparent that by immobilising reagents or catalysts onto polymer particles, it was possible to recover the material in the same fashion. Ultimately, Merrifield was awarded the Nobel Prize for Chemistry in 1984 "for his development of methodology for chemical synthesis on a solid matrix".
Evolution
The basic approach to SPS has remained unchanged during the last 40 years, although a number of improvements and modifications to the chemistry have been introduced. These include using different types of protecting group, alternative linkers (compounds used to enable the attachment and ultimate release of material to the polymer particles), and of course the introduction of microcomputers to act as controlling devices. In the vast majority of cases the underlying polymer particle has remained the same - one per cent or two per cent cross-linked polystyrene. Early on, Merrifield recognised the need to utilise as much of the particle as possible in order to produce a worthwhile amount of material. Simply relying on the external surface of the spherical beads was insufficient. His goal of synthesising a peptide required him to use a polymer which had the ability to actually contain a molecule of reasonable size - hence he concentrated his efforts on evaluating chromatography resins. After trying several types of material he eventually concluded that polystyrene had the correct combination of characteristics:
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