Merrifield and Sieber Amide for Boc SPPS
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.
Boc/Bzl
protection scheme
HF
Merrifield cleavage
1% TFA
Sieber mild amide
0.5–1.3
mmol/g (typical)
MBHA
Sieber base resin
Boc chemistry and mild-acid amide
Merrifield resin (chloromethylated polystyrene) is loaded via benzyl ester formation under Boc strategies. Final cleavage/deprotection typically uses anhydrous HF or TFMSA with scavengers—requiring appropriate engineering and training.
Sieber Amide resins combine MBHA with the Sieber linker oxazolidine, enabling cleavage of Boc-protected peptidyl amides with dilute TFA (often ~1%) while retaining side-chain benzyl protections for fragment or late-stage handling.
Typical specifications
Merrifield matrix
Chloromethyl polystyrene–DVB
Boc peptide acids
Sieber matrix
MBHA polystyrene
Boc peptide amides
Loading
0.5–1.3 mmol/g (Merrifield)
Assayed per lot
Sieber loading
0.3–0.8 mmol/g
Linker pre-installed
Merrifield cleavage
HF or TFMSA
Facility-dependent
Sieber cleavage
~0.5–2% TFA/DCM
Protected amide product
Fmoc alternative
Use Wang / Rink
Different protecting groups
Figures are indicative industry-typical values. Lot- and project-specific data appear on the quotation and certificate of analysis.
When Merrifield vs Sieber Amide
| Goal | Resin | Cleavage outcome |
|---|---|---|
| Boc peptide acid | Merrifield | HF/TFMSA → free acid + Bzl off |
| Boc peptide amide (global HF) | MBHA / PAM variants | HF → amide (facility choice) |
| Boc protected amide fragment | Sieber Amide | Mild TFA → amidated + side chains protected |
| Fmoc/tBu discovery | Wang / Rink | Not Merrifield/Sieber primary use |
Figures are indicative industry-typical values. Lot- and project-specific data appear on the quotation and certificate of analysis.
Indicative Sieber mild cleavage
For Boc-protected C-terminal amides. HF workflows for Merrifield are facility-specific and not detailed here.
- 01
Wash Sieber peptidyl-resin with DCM.
- 02
Treat with 0.5–1% TFA in DCM, ~10 mL/g, 15–30 min with gentle mixing.
- 03
Drain and wash resin with DCM; combine organic phases.
- 04
Concentrate, triturate, and dry protected amide under vacuum.
- 05
Confirm structure before global deprotection or ligation.
Boc resin workflow
Confirm protecting scheme
Boc SPPS uses TFA deprotection in cycle; Merrifield/Sieber are not interchangeable with Fmoc resins without chemistry change.
Load and extend
Boc-AA coupling with DIC or carbodiimide; His(Trt), Arg(Tos), etc. per Boc map.
Cleavage path
HF/TFMSA for Merrifield acids; mild TFA for Sieber protected amides.
Safety and compliance
HF handling only in qualified areas; document scavengers and waste streams.
What you receive
- Merrifield or Sieber Amide lot COA with loading and mesh
- Linker identification (chloromethyl vs Sieber) on paperwork
- Storage conditions and compatibility notes
- Regulatory-ready lot trace for GMP inquiries on request
- Quotation by resin type and quantity
Frequently asked questions
Not as standard practice. Merrifield targets Boc/Bzl. Fmoc labs should use Wang, 2-CTC, or Rink.
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 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 details2-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 detailsReady to specify this for your program?
Share sequence, scale and documentation needs. We reply with indicative specs and a project-specific quotation.