Wang resin for Fmoc C-terminal acids
p-Alkoxybenzyl alcohol linker on polystyrene–DVB. The workhorse support for Fmoc SPPS of peptides with a free C-terminal carboxylic acid, cleaved in concentrated TFA with scavengers.
0.3–1.2
mmol/g loading
100–200
mesh (typical)
1%
DVB crosslinking
TFA
cleavage cocktail
C-acid
terminus delivered
Linker chemistry
Wang resin carries a 4-alkoxybenzyl alcohol handle. The first Fmoc-amino acid is esterified onto the benzyl alcohol; subsequent cycles follow standard Fmoc/tBu SPPS. Final cleavage with TFA releases the peptide as a C-terminal acid and simultaneously removes acid-labile side-chain protecting groups.
Compared with 2-CTC, Wang requires stronger acid and is less suitable when you need a fully protected fragment or when the C-terminal residue is prone to diketopiperazine during Fmoc deprotection. It remains the default when you want a free acid after a standard TFA workup.
Typical specifications
Lot certificates list measured loading, mesh and swelling. Ranges below are indicative of commercial polystyrene Wang resins.
Matrix
Polystyrene–DVB
1% DVB typical for lab scale
Linker
p-Alkoxybenzyl alcohol (Wang)
Acid-labile benzyl ester
Loading
0.3–1.2 mmol/g
Lower loading for long / difficult sequences
Mesh
100–200 or 200–400
Coarser mesh for large reactors
Swelling (DCM)
~4–6 mL/g
Check DMF/NMP for SPPS
Cleavage
95% TFA + scavengers
1–3 h typical; residue-dependent
C-terminus
Carboxylic acid
Not for C-terminal amides
Figures are indicative industry-typical values. Lot- and project-specific data appear on the quotation and certificate of analysis.
C-terminal residue considerations
First-residue choice affects racemization on loading and diketopiperazine risk during Fmoc deprotection of dipeptides on Wang.
| C-terminal residue | Risk | Guidance |
|---|---|---|
| Pro, Gly | DKP formation | Prefer 2-CTC or load as pre-formed dipeptide; minimize piperidine contact time |
| Cys, His | Racemization on loading | Use pre-loaded Wang or mild esterification protocols; avoid strong bases |
| Asp, Glu | Side-chain ester migration | Standard tBu protection; monitor aspartimide in Asp-Gly motifs |
| Standard AA | Low | Wang is appropriate for routine C-terminal acids |
Figures are indicative industry-typical values. Lot- and project-specific data appear on the quotation and certificate of analysis.
Indicative cleavage protocol
Always optimize scavengers to the sequence (Trp, Met, Cys, Arg). The cocktail below is a common starting point.
- 01
Wash the peptidyl-resin with DCM, then dry under vacuum or nitrogen.
- 02
Treat with TFA / TIS / water (95:2.5:2.5) or TFA / EDT / water / TIS as required by the sequence, ~10 mL/g resin.
- 03
Agitate 1–3 hours at room temperature; filter and wash the resin with fresh TFA.
- 04
Precipitate the peptide in cold diethyl ether or MTBE, centrifuge, wash, and lyophilize from aqueous TFA or AcOH.
- 05
Confirm identity and purity by HPLC and LC-MS before further purification.
How teams use Wang resin
Select loading and mesh
Lower loading (≤0.5 mmol/g) for sequences >30 residues or aggregation-prone stretches; higher loading for short peptides where throughput matters.
Load or buy pre-loaded
Esterify the first Fmoc-AA in-house, or start from pre-loaded Fmoc-AA-Wang to skip racemization-prone first coupling.
Assemble by Fmoc SPPS
Standard DIC/Oxyma or HATU protocols in DMF or NMP; double-couple difficult positions as needed.
Cleave, purify, document
TFA cleavage with scavengers, RP-HPLC purification, and a COA with loading and residual solvent data for the resin lot used.
What you receive
- Resin lot with stated loading (mmol/g) and mesh
- Certificate of analysis: appearance, loading assay, % DVB where reported
- Storage guidance (cool, dry; protect from light and moisture)
- Optional: swelling data in DCM/DMF on request
- Quote reference tied to mesh, loading band and pack size
Frequently asked questions
No. Wang releases a carboxylic acid. For C-terminal amides use Rink Amide (AM or MBHA) or Sieber Amide for mild cleavage of protected amides.
Related
2-Chlorotrityl (2-CTC)
Trityl chloride linker on polystyrene–DVB forms acid-labile benzyl esters. 2-CTC is the default when you need protected peptide fragments, acid-sensitive motifs, or lower diketopiperazine risk at the C-terminus than on Wang.
View detailsPre-loaded Wang
Fmoc-amino acids esterified on Wang with lot-documented loading. Skips the racemization-prone first coupling and accelerates campaigns where the C-terminal residue is His, Cys, or otherwise sensitive to manual loading.
View detailsRink Amide AM / MBHA
para-(Rink amide) benzyl ester supports deliver peptides with C-terminal CONH2 after TFA cleavage. Choose AM (aminomethyl) for standard lengths or MBHA (4-methylbenzhydrylamine) when higher swelling and softer aggregation help long or difficult sequences.
View detailsEthyl & Methyl Indole Resins
Indole-derived linkers on polystyrene enable C-terminal N-ethyl and N-methyl carboxamides after TFA cleavage—motifs common in GnRH analogs such as leuprolide. Chemistry differs from Rink: first coupling to the linker is inefficient under carbodiimide alone; HATU (or similar uronium) is required.
View detailsReady to specify this for your program?
Share sequence, scale and documentation needs. We reply with indicative specs and a project-specific quotation.