2-Chlorotrityl chloride Resin

2-Chlorotrityl Chloride Resin: Acid-Labile Resin for Protected Peptide Synthesis

2-Chlorotrityl Chloride Resin is a mildly acid-labile, polystyrene-based solid support used in Fmoc solid-phase peptide synthesis (SPPS), particularly when protected peptides or fragments with a C-terminal carboxylic acid are desired. Functionalized with 2-chlorotrityl chloride groups, this resin forms an ester bond with the carboxylic acid of the first amino acid or building block.

Unlike traditional Wang or Rink resins, peptides synthesized on 2-chlorotrityl resin can be cleaved under mild acidic conditions, preserving side-chain protecting groups. This makes it ideal for fragment synthesis, peptidomimetics, and stepwise convergent assembly.

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Product Specifications

• Matrix: Polystyrene cross-linked with ~1% divinylbenzene (DVB)

• Functional Group: 2-Chlorotrityl chloride

• Loading: Typically 0.5–1.5 mmol/g (available in low, medium, or high loading variants)

• Particle Size: Usually 100–200 mesh (~75–150 µm)

• Swelling: Good in DCM, DMF, NMP, THF

• Linkage Type: Acid-labile benzylic ester

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Key Features

• Mild Cleavage Conditions: Enables early-stage cleavage using dilute TFA or acetic acid, preserving side-chain protections.

• C-Terminal Carboxylic Acids: Yields peptides with a free –COOH group.

• Versatile Use: Excellent for protected peptide fragments, difficult sequences, and non-peptide small molecules.

• Reduced Aggregation Risk: Especially in low-loading formats, it’s well-suited for hydrophobic or aggregation-prone sequences.

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Applications

• Synthesis of protected peptide fragments for convergent peptide assembly

• Combinatorial library synthesis

• Peptidomimetic and small molecule synthesis

• Side-chain protected peptides for ligation or further synthetic transformations

• Fmoc SPPS workflows requiring gentle cleavage conditions

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Cleavage Conditions

• Partial cleavage (retaining side-chain protection):
  1–5% TFA in DCM for 1–2 hours at room temperature
  (Often with scavengers like triethylsilane or water)

• Full cleavage (removing side-chain protecting groups):
  Standard TFA cocktail (e.g., 95% TFA, 2.5% water, 2.5% TIS) for 1–3 hours

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Handling & Storage

• Air-sensitive: Store dry under inert atmosphere (e.g., nitrogen or argon)

• Moisture-sensitive: Keep tightly sealed and protected from humidity

• Pre-use activation: Pre-swell in DCM or DMF before amino acid loading

• Unreacted sites: After loading, cap residual chloride groups with methanol or another nucleophile to prevent side reactions

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Advantages vs. Other Resins