2-Chlorotrityl resin for mild cleavage and protected fragments
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.
0.4–1.0
mmol/g loading
1–3%
TFA in DCM cleavage
Fragment
Fmoc/tBu intact
↓ DKP
vs Wang (Pro/Gly)
100–200
mesh (typical)
Mild cleavage and fragments
The first amino acid is loaded as an ester to the trityl group. Treatment with 1–3% TFA in DCM (or dilute AcOH/DCM) cleaves the peptide–linker bond without removing Fmoc or tBu protections, yielding isolable segments for peptide ligation or hybrid approaches.
When the end product is a free C-terminal acid with deprotected side chains, a second global deprotection in standard TFA scavenger cocktails follows mild cleavage. The linker’s bulk and reduced nitrogen accessibility at the resin-bound C-terminus mitigate cyclization to diketopiperazine during the first piperidine deprotection relative to Wang, especially for C-terminal Pro and Gly.
Typical specifications
Indicative commercial ranges. Binding values are on the lot COA.
Matrix
Polystyrene–DVB
1% DVB typical
Linker
2-Chlorotrityl chloride
Ester attachment after loading
Loading
0.4–1.0 mmol/g
30–50% of max loading common
Mesh
100–200 / 200–400
Scale-dependent
Swelling (DMF)
~4–6 mL/g
Sequence-dependent
Mild cleavage
1–3% TFA/DCM
15–60 min; 1% AcOH/DCM alternative
Global cleavage
TFA + scavengers
Optional second step
Figures are indicative industry-typical values. Lot- and project-specific data appear on the quotation and certificate of analysis.
C-terminal residue risk table
Use this when choosing 2-CTC loading and when comparing against Wang for the first residue.
| C-terminal residue | Primary risk | Guidance on 2-CTC |
|---|---|---|
| Pro | DKP after Fmoc removal | Preferred over Wang for many teams; keep piperidine exposure short; monitor LC-MS for DKP |
| Gly | DKP, epimerization | 2-CTC or pre-formed dipeptide load; pre-loaded 2-CTC for reproducibility |
| His, Cys | Racemization on loading | Use pre-loaded 2-CTC or DIC/HOBt at 0°C; avoid excess DIPEA |
| Asp, Glu | Asaptimide (later) | Mild cleavage preserves tBu for fragment export; watch Asp-Gly in full sequence |
| Other Fmoc-AA | Low–moderate | Routine on 2-CTC; choose loading band by length and aggregation |
Figures are indicative industry-typical values. Lot- and project-specific data appear on the quotation and certificate of analysis.
DKP advantage vs Wang
Indicative relative risk during the first Fmoc deprotection of the resin-bound dipeptide—not a guarantee for every sequence.
| Factor | Wang | 2-CTC |
|---|---|---|
| C-terminal Pro | Higher DKP tendency | Lower tendency; still sequence-dependent |
| C-terminal Gly | Higher DKP tendency | Often improved; dipeptide load still best for critical jobs |
| Cleavage strength | 95% TFA global | 1–3% TFA for protected fragment |
| Convergent synthesis | Poor (deprotects) | Designed for protected segments |
| Throughput acids | Faster one-pot | Extra mild step if fragment route |
Figures are indicative industry-typical values. Lot- and project-specific data appear on the quotation and certificate of analysis.
Indicative mild cleavage protocol
For Fmoc/tBu–protected fragments. Adjust time and acid strength to sequence labile bonds.
- 01
Wash peptidyl-resin with DCM (3×) and drain.
- 02
Treat with 1–2% TFA in DCM, ~10 mL/g, gentle agitation 20–45 min at room temperature.
- 03
Filter resin; combine filtrates and concentrate under reduced pressure.
- 04
Triturate with cold ether or precipitate into cold MeOH/water; dry under vacuum.
- 05
Confirm by LC-MS; store fragment protected from moisture and light.
Typical 2-CTC workflow
Load or order pre-loaded
Manual loading with Fmoc-AA and mild coupling reagents, or start from Pre-loaded 2-CTC with COA loading.
Extend by Fmoc SPPS
Standard cycles in DMF/NMP; consider lower loading for long or β-sheet–prone sequences.
Mild or global cleave
Mild acid for fragments; global TFA when you need fully deprotected acid in one release.
Purify and qualify
RP-HPLC, LC-MS, and retained aliquot of resin for cleavage yield checks if required.
What you receive
- 2-CTC resin lot with nominal and assayed loading (mmol/g)
- COA: mesh, appearance, loading method, storage conditions
- Handling notes for moisture sensitivity of chlorotrityl chloride
- Cross-reference to compatible pre-loaded SKUs
- Quote tied to loading band, mesh and pack size
Frequently asked questions
Typically 1–3% TFA in DCM or 1–2% AcOH in DCM for 15–60 minutes. Stronger acid or longer times begin removing tBu groups.
Related
Wang Resin
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.
View detailsPre-loaded 2-CTC
Fmoc-amino acids on 2-chlorotrityl resin with verified loading. Ideal starting point for protected fragments, C-terminal Pro/Gly sequences, and projects that combine mild cleavage with skip-the-first-load convenience.
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 detailsMerrifield & Sieber Amide
Merrifield polystyrene anchors Boc/Bzl peptide synthesis with HF or TFMSA cleavage. Sieber Amide adds a mild-acid–labile linker on aminomethyl resin for Boc-protected C-terminal carboxamides released without HF.
View detailsReady to specify this for your program?
Share sequence, scale and documentation needs. We reply with indicative specs and a project-specific quotation.