Continuous-flow solid (gel)-phase peptide synthesis using unsupported ultrahigh-load polymers: Fmoc/t-butyl strategy

The technique of continuous-flow solid-phase peptide synthesis using unsupported polymers has been extended to cover the use of N alpha-Fmoc protected amino acids. This approach to peptide synthesis uses (but is not limited to) a phenolic bead-form polymer at 5 mmol g-1 loading. The success of the technique is based upon "layered displacement" to efficiently remove spent reagents and washing solutions from within the flow reactor under low pressure conditions. This system has been successfully employed in synthesizing the test peptides, [Leu5]-enkephalin, neurotensin and the notoriously difficult decapeptide sequence (65-74) of the acyl carrier protein.