Minimal Protection Strategies for Solid-Phase Peptide Synthesis

This technical report presents a minimal protection strategy for solid-phase peptide synthesis (SPPS), focusing on the synthesis of a novel peptide-drug conjugate. The report outlines the advantages of SPPS, including efficient couplings and the elimination of purification steps for intermediates. However, it also discusses the challenges posed by the need to protect certain amino acid side chains from undesired reactivity, which can lower atom economy and yield. The study highlights the dominance of Fmoc-SPPS due to its milder reaction conditions and reduced reliance on hazardous chemicals like trifluoroacetic acid (TFA). The report details the methodology employed in both conventional and minimal protection approaches, emphasizing the environmental benefits of reducing solvent utilization and hazardous waste. Additionally, it compares the crude purity and atom economy achieved through these methods, demonstrating significant improvements in the minimal protection strategy. Future studies are anticipated to explore further applications of this approach in peptide synthesis.