A method is suggested for the synthesis of multicomponent peptide mixtures. The method is a solid phase synthesis modified in order to give a closely equimolar mixture of peptides with predetermined sequences. The main point of modification is that before every coupling cycle the resin is divided into equal parts and each portion is coupled with a different amino acid. Then the portions are mixed and before the next coupling cycle the resin is again distributed into equal portions. The method is illustrated by the synthesis of a mixture of 27 tetrapeptides and that of 180 pentapeptides.

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The paper describes and compares the utility of the three chemical methods used for the synthesis of combinatorial libraries: (1) the mixed reactant method, (2) the portioningmixing method, and (3) light-directed synthesis. It also deals with historical aspects of these methods and with the most important screening methods ascociated with them. Q 1995 WII~Y-IIS, inc