Fmoc-Pro-Wang Resin

Fmoc-Pro-Wang Resin
Nα-Fmoc-L-proline esterified to Wang (4-alkoxybenzyl alcohol) resin; 100–200 mesh, 0.3–0.8 mmol/g

Wang resin preloaded with Fmoc-Pro-OH, for making peptide acids with a C-terminal proline by Fmoc SPPS. Remove the Fmoc group with 20% piperidine in DMF and build the chain as usual; 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). The loading for each lot is on its certificate of analysis.

A C-terminal proline on an alkoxybenzyl ester resin is the classic diketopiperazine case: once the second residue has been coupled to the proline and its Fmoc group removed, that residue’s free amine can attack the ester bond joining proline to the resin, and the dipeptide leaves as a diketopiperazine. Couple the third residue promptly after that Fmoc removal, keep the deprotection no longer than it needs, and for sequences that lose badly consider 2-chlorotrityl resin, which reduces the loss without eliminating it. Proline’s secondary amine also couples more slowly than a primary amine, so the second residue may need a longer or a repeated coupling. Starting from a preloaded resin also avoids esterifying the first amino acid yourself, the step in which the C-terminal residue is most readily racemized.

Applications

• Peptide acids with a C-terminal proline
• Proline-rich and polyproline sequences
• Manual and automated synthesis

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

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. 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
3. Fields GB et al. Solid phase peptide synthesis utilizing 9‐fluorenylmethoxycarbonyl amino acids. International Journal of Peptide and Protein Research 1990, 35, 161–214. doi:10.1111/j.1399-3011.1990.tb00939.x

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