Automatic synthesis and application of cyclic disulfide bonded bridge peptides

Cyclic disulfide-bridged peptides with good purity can be rapidly prepared using microwave-enhanced polypeptide solid-phase synthesis (SPPS).

Brief introduction

Figure 1 Left: Fmoc-(S)-Cys(Mmt)-OH;

Right: Fmoc-(S)-Cys(STmp)-OH

Materials and methods

reagent

Figure 2: Oxytocin

Peptide synthesis: THR-123, CYFDDSSNVLCKKYRS-CO2H

Synthesize peptides at a scale of 0.

Figure 3: THR-123

Synthesize peptides at 0.

Figure 4: CHEC-7

Polypeptide synthesis: Conotoxin-SI, ICCNPACGPKYSC-NH2

Synthesize peptides at a scale of 0.

Figure 5: Conotoxin-SI

outcome

Microwave-enhanced SPPS was used on the Liberty Blue Automated Microwave Peptide Synthesizer to produce synthetic oxytocin, resulting in a 69% purity of the peptide of interest (Figure 6

Figure 6: UPLC chromatogram of oxytocin

THR-123 was synthesized using microwave-enhanced SPPS on the Liberty Blue Automated Microwave Peptide Synthesizer, resulting in a 77% purity of the peptide of interest (Figure 7).

Figure 7: UPLC chromatogram of THR-123

CHEC-7 was synthesized using microwave-enhanced SPPS on the Liberty Blue Automated Microwave Peptide Synthesizer, yielding an 80% purity peptide of interest (Figure 8).

Figure 8: UPLC chromatogram of CHEC-7

Figure 9: Peak mass spectrogram with a retention time of 5.

Figure 10: Peak mass spectrometry with a retention time of 5.

Spirotoxin-SI was synthesized using microwave-enhanced SPPS on the Liberty Blue Automated Microwave Peptide Synthesizer, resulting in a 67% purity of the peptide of interest (Figure 11).

Figure 11: UPLC chromatogram of Conotoxin-SI

conclusion

Disulfide bond bridged cyclic peptides can be synthesized quickly and efficiently using automated microwave-enhanced polypeptide

References

[1] Lee, H.

[2] Sugimoto, H.

[3] Cunningham, T.
J.
; Greenstein, J.
; Yao, L.
; Fischer, I.
; Connors, T.
Rejuvenation Res.
2018, rej.
2017.
2049.
[4] Azam, L.
; McIntosh, J.
M.
Acta Pharmacol.
Sin.
2009, 30 (6), 771–783.

[5] Góngora-Benítez, M.
; Tulla-Puche, J.
; Albericio, F.
Chem.
Rev.
2014, 114 (2), 901–926.

[6] Adessi, C.
; Soto, C.
Curr.
Med.
Chem.
2002, 9 (9), 963–978.

[7] Postma, T.
M.
; Albericio, F.
Org.
Lett.
2013, 15 (3), 616–619.

[8] CEM Application Note (AP0124) - “CarboMAX - Enhanced Peptide Coupling at Elevated Temperature”.

[9] CEM Technical Note (P/N: 600837) - “Cl-MPA ProTide and Cl-TCP(Cl) ProTide Resin Loading and Protected Cleavage Procedures”.