Random Split-and-Pool Method

The split-and-pool method was presented for the first time in 1988 by Arpad Fuika at two 

At that time, the method was designed to synthesize equimolar mixtures of peptides. However, the consequences of the split-and-pool method were more far-reaching. The same concept was later independently used by Kit Lam for his OBOC concept and Richard Houghten for the synthesis of organized mixtures of peptides. 

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The concept of reducing the number of reaction vessels and exponentially increasing the number of synthesized compounds was brought to a next level of simplicity by the split-and-pool method of Furka et al.5 The split-and-pool method was independently applied by Lam et al.6 in a one-bead-one-compound concept for the combinatorial synthesis of large compound arrays (libraries) and by Houghten et al.7 for the iterative libraries. Now several millions peptides could be synthesized in a few days. In Furka s method the resin beads receiving the same amino acid were contained in one reaction vessel—identical to Frank s method—however, the beads were pooled and then split randomly before each combinatorial step. Thus the method is referred to as the random split-and-pool method to differentiate it from Frank s method in which each solid-phase particle was directed into a particular reaction vessel (the directed split-and-pool method). 

There exist two modifications of the split-and-pool concept the directed and random split-and-pool methods. The key differences are as follows ... 

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