Parallel multipin method

Crowns can be locked into an array format for multiple parallel handling and ready identification (i.e., the Multipin method, as shown in Figure 6.1). 

The execution of the parallel synthesis of up to 96 single compounds by the Multipin method involves pipetting the reactants to each well of a 96-well microtiter plate. The pin array is then placed on top of the plate and the resin is allowed to incubate with the reactants to perform the coupling step. The reaction temperature can be raised to 90°C by placing the reaction block into an incubator. Following each reaction step, the pin array is removed and treated in batch to wash the solid support. These operations are repeated until the desired combinatorial synthesis is completed. The resulting compounds can then be removed from the pins into individual wells on a microtiter plate, each of which ideally contains one single compound. 

Combinatorial libraries are prepared by the (1) parallel synthesis of arrays, (2) split-pool method, (3) biological method, or (4) spatially addressable parallel synthesis [74,78-80]. Parallel synthesis is carried out by the simultaneous synthesis of an array of different compounds. Several methods are available. In the multipin method, the peptide synthesis is carried out on polyethylene rods that have attached protected amino acids [81]. The amino acid sequence of a synthesized peptide on a particular pin depends on the order in which the amino acids are added. The number of products synthesized is the same as the number of pins. Another version of parallel synthesis, known as the teabag method, uses resin-filled bags in place of pins [74]. By pooling the resin portions from the appropriate bags, followed by redistribution and further coupling with a specific amino acid, a peptide library can be synthesized. The SPOT method uses a cellulose paper membrane as a solid support, which acts as an open reactor. Respective reagent solutions are pipetted onto several spots to synthesize as many peptides as the spots chosen [74,82]. 

---