Solid-Phase Synthesis

Protocols for peptide assembly on solid support. The Lokey Lab primarily uses Fmoc/tBu chemistry on 2-chlorotrityl resin, with synthesis performed on the Prelude peptide synthesizer or manually in fritted synthesis vessels.

Protocols

• Coupling Reactions —Overview of amide, ester, and peptoid coupling methods.
• N-Methylation —Fmoc N-methylation via the oxazolidinone route.
• In-Sequence Methylation —On-resin methylation of the terminal residue using Mitsunobu chemistry.
• Sidechain Tyrosine Resin Loading —Loading Fmoc-O-Allyl-Tyrosine through the sidechain for on-resin cyclization.
• Esterification —Solid-phase ester bond formation for depsipeptide synthesis.
• Peptoid Coupling —Bromoacetic acid/DIC method for peptoid residue incorporation.
• BTC Coupling —Triphosgene-mediated coupling for difficult amide bonds.