Silica-Assisted Solid-Phase Peptide Synthesis (SiPPS)

Abstract

Non-swelling silica-based resin was used for peptide synthesis. The strategy used is similar to that of solid-phase peptide synthesis (SPPS), referred to as silica-assisted solid-phase peptide synthesis (SiPPS). A 2-h coupling seemed to favor the coupling compared to that of 1-h standard coupling. The use of this non-swelling resin allows a 50% reduction in the consumption of solvents. The strategy was well demonstrated for the synthesis of H-YSSFL-NH₂, linear oxytocin, angiotensin II, and afamelanotide using a silica-based support (Fmoc-Rink amide SiliaBond manufactured from SiliCycle Inc.). The peptides were found to have more than acceptable purity, although there was a loss in overall yields.

Keywords: afamelanotide; angiotensin II; linear oxytocin; non‐swelling; peptide synthesis; silica resin.

SCHEME 1

Anchoring of Fmoc‐Rink‐Amide linker onto the amino‐SiliCycle resin.

SCHEME 2

Peptide synthesis using Rink‐Amide SiliCycle resin (SiPPS).

FIGURE 1

HPLC chromatogram for H‐YSSFL‐NH₂ synthesized by SiPPS with 1‐h and 2‐h coupling, respectively. Method: 5%–95% B into A in 15 min, 220 nm.

FIGURE 2

HPLC chromatogram of linear oxytocin synthesized by SiPPS using 2‐h protocol. Method: 5%–60% B into A in 15 min, 220 nm.

FIGURE 3

HPLC chromatogram of angiotensin II synthesized by SiPPS using 2‐h protocol. Method: 5%–95% B into A in 15 min, 220 nm.

FIGURE 4

HPLC chromatogram of afamelanotide synthesized using 2‐h protocol. Method: 5%–95% B into A in 15 min, 220 nm.