Solid-Phase Organic Synthesis (Chemistry) by Burgess
Translation to solid-phase synthesis was facilitated by the use of a tert-butyldiarylsilyl (TBDAS) linker that closely mimics the tert-butyldiphenysilyl protecting group used in the original solution-phase route development work.
Custom Peptide Synthesis, Solid phase peptide synthesis
Fmoc chemistry was developed by Eric Atherton and Bob Sheppard at the Laboratory of Molecular Biology in Cambridge in the late 1970’s and has been reviewed by Chan and (Fmoc Solid Phase Peptide Synthesis – A Practical Approach. Oxford University Press, 2000).
In Fmoc solid-phase peptide synthesis, the peptide chain is assembled stepwise, one amino acid at a time, while attached to an insoluble resin support. This allows the reaction by-products to be removed at each step by simple washing. Amino acids are protected at their amino terminus by the Fmoc (9-fluorenylmethoxycarbonyl) group and coupled to the growing chain after activation of the carboxylic acid terminus. The Fmoc group is then removed by piperidine treatment and the process repeated. After the peptide has been assembled it is removed from the resin by treatment with trifluoroacetic acid (TFA). At the same time, protecting groups on amino acid side chains are also removed yielding the crude linear peptide. One-step purification by reverse-phase HPLC is often sufficient to obtain the peptide in >95% purity.