Getting to Know Fmoc-Lys(Mtt)-Wang Resin (100–200 Mesh)

If you’re diving into more advanced peptide syntheses, you’ll eventually come across Fmoc-Lys(Mtt)-Wang Resin. It's a super useful tool, especially when you need a protected lysine sitting at the C-terminus of your peptide — and when you want side-chain flexibility later on.

Let’s unpack what it’s all about

 What Is Fmoc-Lys(Mtt)-Wang Resin?

Breaking the name down:

• Fmoc: Protects the α-amine of lysine during peptide chain elongation.

• Lys(Mtt): You’ve got a lysine residue where the side-chain ε-amine is protected with an Mtt group (4-methyltrityl).
  → Mtt is special because it’s acid-labile but milder than other protecting groups — you can selectively remove it without touching the main chain!

• Wang resin: A polystyrene resin functionalized with a Wang linker, allowing for TFA cleavage at the end.

• 100–200 mesh: Refers to particle size. This range (~75–150 μm) is standard for peptide synthesis, providing a good surface area and resin swelling properties.

 What It’s Used For

• Solid-phase peptide synthesis (SPPS) where you want lysine at the C-terminus.

• Orthogonal protection strategies — since you can remove the Mtt group mid-synthesis without disturbing the Fmoc protection or cleaving the peptide off the resin.

• Great for making branched, cyclic, or modified peptides where side-chain manipulation is needed.

 How It Works in Practice

1. Deprotect Fmoc with piperidine → frees the α-amine.

2. Build the peptide chain as usual.

3. Optionally deprotect the Mtt group (using dilute TFA in DCM, usually 1–3% TFA) mid-synthesis to functionalize the lysine side chain.

4. Cleavage from resin with strong TFA (typically ~95% TFA) after synthesis is complete.

Mtt Side-Note: Be cautious—Mtt deprotection releases colored byproducts (yellow-orange). You’ll see it happening!

 Storage & Handling

• Keep dry and protected from light.

• Store under nitrogen or argon if possible.

• Pre-swell in DCM, DMF, or NMP before synthesis for best results.

 Quick Tips

• Check loading: Knowing your resin’s loading (~0.4–0.7 mmol/g typically) helps in calculating accurate equivalents.

• Use fresh solvents: Moisture or degraded DMF can mess with coupling efficiency.

• Plan for Mtt removal: Have a plan ready if you need to functionalize the lysine side chain.

 Final Thoughts

Fmoc-Lys(Mtt)-Wang Resin is a real game-changer if you’re working with more sophisticated peptide architectures. It gives you the power to modify the side chain independently from the main chain — a perfect setup for peptides with multiple functional handles.

Master it, and you’ll unlock a whole new level of peptide creativity.

Would you like me to also sketch out a simple workflow diagram showing how this resin is used during synthesis?  (I can make it visual if you want!