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Background <p>Solid phase peptide synthesis is a standard synthetic strategy for peptides at both academic and industry level. Due to the high consumption of solvents, the Process Mass Index (PMI) and complete environmental factor (cEF) remain very high. In fact, &gt; 80% of waste is generated due to washing of resin after coupling and Fmoc removal.</p> Objective <p>To modify standard SPPS protocol for the synthesis of hydrophobic and aggregating peptides to minimize solvent consumption, followed by evaluating their antimicrobial activity.</p> Methods <p>In-situ Fmoc removal approach for peptide synthesis allows the elimination (or reduction) of washing step, which lowers the solvent waste significantly. Herein, we report the synthesis of antimicrobial peptides (<b>P3</b>, <b>P4</b> and <b>P5</b>) designed from human SPLUNC1 protein and C-terminal domain of calgranulin C.</p> Results <p>These peptides contain a stretch of hydrophobic amino acids along with charged amino acids which increase the chances of aggregation. This modified in situ Fmoc removal approach helps in the handling of reaction during SPPS, thereby making the peptide synthesis efficient. The washing involving 1% OxymaPure plays a crucial role in this case also to reduce the solvent consumption. The PMI was found to be 892.4, 880.9 and 854.5 for <b>P3</b>, <b>P4</b> and <b>P5</b>, respectively. Further, these peptides were evaluated for <i>in-vitro</i> antimicrobial activity and <b>P3</b> was found to be equipotent to that of colistin standard.</p> Conclusion <p>We envisaged that this new modification in Fmoc in situ removal condition opens a broader perspective for the sustainable synthesis of longer and hydrophobic peptides. Even evaluation of green solvents will help to make the process more sustainable and environmentally friendly.</p> Graphical Abstract <p></p>

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Modified SPPS Protocol for the Synthesis of Novel Antimicrobial Peptides

  • 期刊论文

  • 发表日期：

    2025年4月21日

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  • Dinesh Anguraj,
  • Shivani Chaudhary,
  • Mukesh Pasupuleti,
  • L. Ravithej Singh,
  • Anamika Sharma

摘要

Background

Solid phase peptide synthesis is a standard synthetic strategy for peptides at both academic and industry level. Due to the high consumption of solvents, the Process Mass Index (PMI) and complete environmental factor (cEF) remain very high. In fact, > 80% of waste is generated due to washing of resin after coupling and Fmoc removal.

Objective

To modify standard SPPS protocol for the synthesis of hydrophobic and aggregating peptides to minimize solvent consumption, followed by evaluating their antimicrobial activity.

Methods

In-situ Fmoc removal approach for peptide synthesis allows the elimination (or reduction) of washing step, which lowers the solvent waste significantly. Herein, we report the synthesis of antimicrobial peptides (P3, P4 and P5) designed from human SPLUNC1 protein and C-terminal domain of calgranulin C.

Results

These peptides contain a stretch of hydrophobic amino acids along with charged amino acids which increase the chances of aggregation. This modified in situ Fmoc removal approach helps in the handling of reaction during SPPS, thereby making the peptide synthesis efficient. The washing involving 1% OxymaPure plays a crucial role in this case also to reduce the solvent consumption. The PMI was found to be 892.4, 880.9 and 854.5 for P3, P4 and P5, respectively. Further, these peptides were evaluated for in-vitro antimicrobial activity and P3 was found to be equipotent to that of colistin standard.

Conclusion

We envisaged that this new modification in Fmoc in situ removal condition opens a broader perspective for the sustainable synthesis of longer and hydrophobic peptides. Even evaluation of green solvents will help to make the process more sustainable and environmentally friendly.

Graphical Abstract