Wang Resin

Wang Resin
Wang resin, 4-benzyloxybenzyl alcohol polystyrene (4-alkoxybenzyl alcohol resin); 100–200 mesh, 0.7–1.3 mmol/g

The standard support for making peptide acids by Fmoc SPPS, supplied unloaded so that the first residue can be chosen freely. Esterify the Fmoc-amino acid onto the benzylic hydroxyl — as the symmetrical anhydride or with DIC and a catalytic amount of DMAP, or with MSNT and N-methylimidazole — then cap any hydroxyl left unreacted, and take the loading from the Fmoc released on the first deprotection. Chain assembly is the usual cycle of 20% piperidine in DMF and coupling, and final cleavage with 95% TFA and scavengers releases the peptide acid and removes the acid-labile side-chain protecting groups (tert-butyl, Boc, trityl, Pbf) in the same step; acid-stable groups need their own deprotection.

That loading step is where the first residue can be lost to racemization: DMAP catalyses it, so keep the DMAP catalytic and the reaction short, and for cysteine or histidine at the C-terminus use a protocol chosen for low racemization, or 2-chlorotrityl resin instead. At the dipeptide stage the free amine can attack the ester bond to the resin and leave as a diketopiperazine. This is most likely when proline or glycine is one of the first two residues; couple the third residue promptly after the second Fmoc removal. 2-Chlorotrityl resin can reduce the loss for such sequences, though not eliminate it.

Applications

• Peptide acids with any chosen C-terminal residue
• Protected and side-chain-anchored building blocks esterified in the laboratory
• Manual, microwave and automated synthesis
• Peptide libraries and parallel synthesis

Storage
Store refrigerated (2–8 °C) and dry, in a tightly closed container.

Published research using P3 BioSystems material

• Lohman RJ et al. Design and development of novel, short, stable dynorphin-based opioid agonists for safer analgesic therapy. Frontiers in Pharmacology 2023. doi:10.3389/fphar.2023.1150313
• Zanjani AAH et al. Amyloid Evolution: Antiparallel Replaced by Parallel. Biophysical Journal 2020. doi:10.1016/j.bpj.2020.03.023

References

1. Wang S. p-Alkoxybenzyl Alcohol Resin and p-Alkoxybenzyloxycarbonylhydrazide Resin for Solid Phase Synthesis of Protected Peptide Fragments. Journal of the American Chemical Society 1973, 95, 1328–1333. doi:10.1021/ja00785a602
2. Sandhya K et al. A protocol for racemization-free loading of Fmoc-amino acids to Wang resin. Tetrahedron Letters 2008, 49, 2435–2437. doi:10.1016/j.tetlet.2008.02.055
3. Pedroso E et al. Diketopiperazine formation in solid phase peptide synthesis using p-alkoxybenzyl ester resins and Fmoc-amino acids. Tetrahedron Letters 1986, 27, 743–746. doi:10.1016/s0040-4039(00)84089-7

For research use only. Not for human or veterinary use.