Automated Synthesis of Head-to-Tail Cyclic Peptides via Microwave-Enhanced SPPS

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Fully automated synthesis of head-to-tail cyclized peptides can be performed rapidly and with excellent purity using the Liberty Blue and Liberty PRIME peptide synthesizers. Microwave SPPS benefits not only the linear assembly but also the subsequent cyclization step with exceptional purity achieved on a variety of difficult biologically important peptides. The one-pot Fmoc SPPS cycles used on the Liberty PRIME provide even further benefit for synthesis time and waste reduction.


Table 1: Fully automated synthesis of head-to-tail cyclized peptides.

Instrument Sequence Crude Purity Synthesis Time
Liberty Blue cyclo-[GVYLHIE] 78% 2 h 13 min
Liberty Blue cyclo-[WTaRRR-nal-R-Fpa-nle-Q] 75% 3 h 1 min
Liberty PRIME cyclo-[WTaRRR-nal-R-Fpa-nle-Q] 75% 2 h
Liberty PRIME


66% 2 h 5 min
Liberty PRIME


73% 2 h 12 min


Table 2: Comparison of Liberty Blue and Liberty PRIME for the Synthesis of Cyclorasin A

Instrument Peptide Synthesis Time Total Waste Volume
Liberty Blue Cyclorasin A 3 h 1 min 674 mL
Liberty PRIME Cyclorasin A 2 h 584 mL