End-to-end cyclic peptides are automatically synthesized by microwave-enhanced polypeptide solid-phase synthesis

summary

The Liberty Blue™ and Liberty PRIME™ peptide synthesizers enable fast, high-purity, fully automated synthesis of head-tail cyclic peptides

Table 1: Fully automatic synthesis of end-to-end cyclic peptides

Table 2: Liberty Blue and Liberty PRIME synthesize Cyclorasin A¹

introduction

Cyclic peptides are able to bridge the chemical space gap between small molecules and antibodies, allowing the design of molecules with high binding affinity, significant selectivity, low toxicity and the ability to enter intracellular ^targets2

SPPS can prepare end-to-end cyclic peptides

Figure 1: Fmoc-Glu-ODmab (left);

Fmoc-Glu (Wang resin LL) - ODmab (right)

Materials and methods

reagent

The following contains the specified side-chain protection group Fmoc amino acids purchased from CEM Corporation (Matthews, NC) and: Ala, Arg (Pbf), Gly, His (Boc), Ile, Leu, Lys (Boc), Thr (tBu) ), Trp (Boc), Tyr (tBu) and Val

Polypeptide synthesis: CEM 7-mer, cyclo-[GVYLHIE]

Using the CEM Liberty Blue Automated Microwave Peptide Synthesizer, synthesis on Fmoc-Glu(Wang)-ODmab resin (ion exchange capacity: 0.

The coupling reaction is performed

Figure 2: CEM 7-mer

Using the CEM Liberty Liberty Blue automatic microwave polypeptide synthesizer, synthesized at a scale of 0.

Polypeptide synthesis: Cyclorasin A, cyclo-[WTaRRR-nal-R-Fpa-nle-Q] (Liberty PRIME)

Using the CEM Liberty LIBERTY PRIME automated microwave peptide synthesizer, synthesis on a Rink Amide ProTide LL resin (ion exchange capacity: 0.

Figure 3: Cyclorasin A

Synthesis at a scale of 0.

Figure 4: N-Methyl Cyclorain Analog

Using the CEM Liberty PRIME Automatic Microwave Peptide Synthesizer on Fmoc-Glu (Wang)-ODmab resin (ion exchange capacity: 0.

Figure 5: Poly N-Methyl Peptide

Peptides are analyzed on a Waters Acquity UPLC system equipped with a PDA detector equipped with Acquity UPLC BEH C8 columns (1.

outcome

Microwave-enhanced solid-phase synthesis of CEM 7-mer on the Liberty Blue Automated Microwave Peptide Synthesizer yields a 78% purity of the peptide of interest (Figure 6

Figure 6: UPLC chromatogram of CEM 7-mer

Microwave enhancement