Here’s a clean, blog-style breakdown of Fmoc-Ser(tBu)-Wang Resin LL (100–200 mesh)—great for anyone getting into peptide synthesis or looking for a refresher:

Spotlight on Fmoc-Ser(tBu)-Wang Resin LL (100–200 Mesh)

If you’re crafting peptides with serine at the C-terminus, this resin is your best friend. Fmoc-Ser(tBu)-Wang Resin LL combines solid protection strategies with solid performance—perfect for solid-phase peptide synthesis (SPPS) under Fmoc chemistry.

Let’s unpack what makes it special.

 Name Breakdown

• Fmoc: This protects the α-amine of the serine residue during synthesis. It’s base-labile and removed with piperidine.

• Ser(tBu): The amino acid serine is preloaded onto the resin with its hydroxyl side chain protected by a tBu (tert-butyl) group. This protects against unwanted side reactions during synthesis and is removed with TFA at the end.

• Wang resin: The resin backbone uses the acid-labile Wang linker, which allows for C-terminal carboxylic acid formation upon cleavage with TFA.

• LL (Low Loading): Typically ~0.2–0.4 mmol/g. This helps reduce aggregation in longer or more hydrophobic peptides by spacing growing chains further apart.

• 100–200 mesh: Standard particle size (~75–150 μm), balancing good swelling and reaction kinetics.

 What It’s For

• Synthesizing peptides with serine at the C-terminus.

• Avoiding premature reactions at the serine OH group during chain extension.

• Ideal for longer peptides, difficult sequences, or where low resin loading is advantageous.

How It Works in SPPS

1. Swelling: Resin is swollen in a solvent like DCM or DMF.

2. Fmoc deprotection: Treated with piperidine to expose the α-amine.

3. Coupling: Standard coupling chemistry adds the next amino acid.

4. Repeat: Continue chain elongation as needed.

5. Cleavage: Final cleavage with TFA removes:

   • The peptide from the resin (cleaves Wang linker),

   • The tBu protecting group on serine’s side chain,

   • All acid-labile side chain protections in one go.

 Storage Tips

• Store in a cool, dry place (preferably under nitrogen or argon).

• Protect from moisture and light.

• Always pre-swell in solvent before use.

 Pro Tips

• Low loading helps with yield and purity in longer sequences.

• Monitor tBu deprotection—it occurs during TFA cleavage, and you may see a shift in peptide solubility.

• Always check your resin loading before planning equivalents.

 Final Thoughts

Fmoc-Ser(tBu)-Wang Resin LL gives you a gentle, controlled way to build peptides that end with serine—without risking side-chain reactivity mid-synthesis. It’s clean, reliable, and perfect when you’re working with sequences that demand finesse.

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