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Updated: Sep 11, 2025

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Silica-Assisted Solid-Phase Peptide Synthesis (SiPPS).

Nonsikelelo Nkwanyana1, Ashish Kumar1,2, Amit Chakraborty1

  • 1Peptide Science Laboratory, School of Chemistry and Physics, University of KwaZulu-Natal, Durban, South Africa.

Journal of Peptide Science : an Official Publication of the European Peptide Society
|August 16, 2025
PubMed
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This summary is machine-generated.

A novel silica-based resin enables efficient peptide synthesis with reduced solvent use. This silica-assisted solid-phase peptide synthesis (SiPPS) strategy offers a greener alternative for producing complex peptides.

Area of Science:

  • Organic Chemistry
  • Medicinal Chemistry
  • Materials Science

Background:

  • Solid-phase peptide synthesis (SPPS) is a cornerstone of peptide production.
  • Traditional SPPS often relies on swelling resins, leading to significant solvent consumption.
  • Developing alternative supports and strategies is crucial for sustainable chemical synthesis.

Purpose of the Study:

  • To introduce and evaluate a novel silica-assisted solid-phase peptide synthesis (SiPPS) strategy.
  • To demonstrate the efficacy of a non-swelling, silica-based resin for peptide synthesis.
  • To assess the impact of SiPPS on solvent consumption and peptide purity.

Main Methods:

  • Utilized a non-swelling, silica-based resin (Fmoc-Rink amide SiliaBond) for peptide synthesis.
Keywords:
afamelanotideangiotensin IIlinear oxytocinnon‐swellingpeptide synthesissilica resin

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  • Adapted the standard solid-phase peptide synthesis (SPPS) protocol for the silica support.
  • Investigated the effect of extended coupling times (2-h vs. 1-h) on reaction efficiency.
  • Synthesized model peptides including H-YSSFL-NH2, linear oxytocin, angiotensin II, and afamelanotide.

    • Main Results:

    • The silica-assisted solid-phase peptide synthesis (SiPPS) strategy was successfully demonstrated for multiple peptide targets.
    • A 2-hour coupling step showed improved efficiency compared to the standard 1-hour coupling.
    • The non-swelling nature of the silica resin resulted in a 50% reduction in solvent consumption.
    • Synthesized peptides exhibited acceptable purity, though overall yields were slightly reduced.

    Conclusions:

    • Silica-assisted solid-phase peptide synthesis (SiPPS) presents a viable and greener alternative to conventional SPPS.
    • The use of non-swelling silica-based resins significantly reduces solvent waste.
    • Further optimization may be needed to improve overall yields while maintaining purity and sustainability.