Automatic multiple peptide synthesis.

85 I There is a demand for synthetic peptides for inves3-hydroxy-4-0x0 3,4-dihydro-l,2,3-benzotriazine, tigations such as antibody binding studies, synthetic vaccines and peptide antigens. Often only small quantities of material are needed, e.g. 5-10 mg, amounts often below the useful capacity of a conventional peptide synthesizer. Where large numbers of peptides are needed, such as studies of the optimization of peptide antigens, the throughput of a peptide synthesizer is too slow to be of value. Techniques exist for the production of numbers of peptides in milligram quantities [ l , 23. These require careful operator handling plus large volumes of solvents and amino acid reagents. These methods were originally described for use with tert-butoxycarbonyl (tROC) chemistry with its attendant problems of handling corrosive reagents. Other multi-synthesis methods [3] rely on the power of h.p.1.c. to separate the various peptides from each other. Micro solid-phase synthesis on polythene pins [4, 51 can produce very large numbers of peptides; however the microgram amounts and the fact that the peptide remains on the solid-phase support can be a limiting factor in its usefulness. A manual technique is commercially available from Biotech Instruments, Luton, to make up to 48 peptides simultaneously, each on a scale of approximately 5 mg of each peptide. Although successful and easy to use, the method is labour intensive and could be prone to operator error. This paper describes the full automation of the above technique which can be used to make up to 48 different peptides simultaneously, in quantities of 2-20 mg. Solvent and reagent consumption are low; typically only 10 mg of a protected amino acid is required for each addition plus approximately 10 ml of solvent.