High‐Throughput Synthesis of Peptide α‐Thioesters: A Safety Catch Linker Approach Enabling Parallel Hydrogen Fluoride Cleavage

摘要: Peptide -thioesters are fundamental building blocks in peptide and protein science, providing powerful tools for medicinal chemistry. The application of native chemical ligation reactions has enabled synthetic access to cysteine-rich peptides proteins, cyclic as well labeled chemically modified biomolecules. An efficient high-throughput synthesis -thioester would be beneficial many applications that require proteins. Herein we present a novel route using safety catch linker enables parallel strategy synthesis. ACP(68-75), bradykinin dynorphin(1-13) were synthesized via Boc chemistry their thioester form on amide (SCAL), employing polystyrene- or poly(ethylene glycol)-based resins, compartmentalized tea bags. This resin/linker facilitated hydrogen fluoride cleavage which each was subsequently cyclized by ligation, demonstrating the utility this approach. A naturally occurring bioactive peptide, sunflower trypsin inhibitor SFTI-1, demonstrate viability method important