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Solid-Phase Synthesis

In 1963 Merrifield reported the first examples of Solid-phase synthesis of peptides using chloromethylated-polystyrene containing immobilized N-protected amino acids building blocks. This chemistry developed over the ensuing decade and became the basis for much of the progress in peptide chemistry.

The ability to synthesize compounds on an inert polymeric resin bead, to force a reaction to completion by the addition of excess of reagents and monomers, and then remove all the unwanted material by simple filtration and wash it is at the heart of most library synthesis. The use of solid supports for chemical (no peptides and peptide molecules) as well as biological synthesis (proteins, peptides, polynucleotides) relies on three interconnected requirements:
1) A cross-linked, insoluble, polymeric material that is inert to the condition of synthesis.
2) A chemical protection strategy to allow selective orthogonal protection and deprotection of reactive groups in the monomers.
3) Some means of linking the substrate to this solid phase that permits the cleavage of some or the entire product from the solid support during synthesis for analysis of the extent of reaction, and ultimately to give the final product of interest.

| Solution Phase Synthesis | Solid Phase Synthesis | High Throughput Screening |