DIC

Definition

DIC, or Diisopropylcarbodiimide, is a common coupling reagent used in the Merrifield solid-phase method for automated peptide synthesis. It is a key component in the activation and coupling of amino acids during the stepwise construction of peptide chains.

5 Must Know Facts For Your Next Test

1. DIC is used to activate the carboxyl group of an amino acid, making it more reactive towards the amino group of another amino acid during peptide bond formation.
2. The use of DIC in the Merrifield solid-phase method allows for the automated, stepwise synthesis of peptides by repeatedly coupling activated amino acids to the growing peptide chain.
3. DIC forms an O-acylisourea intermediate with the carboxyl group of the amino acid, which then reacts with the amino group of another amino acid to form the peptide bond.
4. The by-product of the DIC-mediated coupling reaction is diisopropylurea, which can be easily removed during the washing steps of the Merrifield solid-phase synthesis.
5. DIC is often used in combination with other coupling agents, such as N-hydroxysuccinimide (HOSu), to improve the efficiency and selectivity of the peptide coupling reaction.

Review Questions

• Explain the role of DIC in the Merrifield solid-phase method for automated peptide synthesis.
  • In the Merrifield solid-phase method, DIC (Diisopropylcarbodiimide) is a crucial coupling reagent used to activate the carboxyl group of an amino acid, enabling it to react with the amino group of another amino acid to form a peptide bond. The activation of the carboxyl group by DIC creates a more reactive species, the O-acylisourea intermediate, which then facilitates the stepwise, automated construction of the peptide chain attached to the insoluble polymeric support. The use of DIC in this method allows for efficient, high-yielding peptide synthesis by repeatedly coupling activated amino acids to the growing peptide chain.
• Describe how DIC and other coupling reagents work to improve the efficiency of peptide bond formation in the Merrifield solid-phase method.
  • Coupling reagents like DIC play a critical role in the Merrifield solid-phase method by activating the carboxyl group of amino acids, making them more reactive towards the amino group of another amino acid. This activation step, typically forming an O-acylisourea intermediate, significantly enhances the rate and selectivity of the peptide bond formation reaction. Additionally, DIC is often used in combination with other coupling agents, such as N-hydroxysuccinimide (HOSu), to further improve the efficiency and yield of the peptide synthesis. The coupling reagents facilitate the stepwise addition of activated amino acids to the growing peptide chain attached to the insoluble polymeric support, enabling the automated, high-throughput production of peptides using the Merrifield solid-phase method.
• Analyze the advantages of using DIC as a coupling reagent in the Merrifield solid-phase method for automated peptide synthesis, and discuss how it contributes to the overall efficiency and versatility of this technique.
  • The use of DIC as a coupling reagent in the Merrifield solid-phase method for automated peptide synthesis offers several key advantages that contribute to the efficiency and versatility of this technique. Firstly, DIC effectively activates the carboxyl group of amino acids, enabling the formation of reactive intermediates that readily react with the amino group of another amino acid to form peptide bonds. This activation step is crucial for the stepwise, automated construction of the peptide chain attached to the insoluble polymeric support. Additionally, DIC is often used in combination with other coupling agents, such as HOSu, to further improve the selectivity and yield of the peptide coupling reactions. The ability to easily remove the diisopropylurea by-product during the washing steps of the Merrifield method also contributes to the overall efficiency and scalability of this automated peptide synthesis approach. Furthermore, the versatility of the Merrifield solid-phase method, facilitated by the use of DIC and other coupling reagents, allows for the rapid and high-throughput production of a wide range of peptide sequences, making it a valuable tool in various fields, including drug discovery, protein engineering, and structural biology.

Related terms

Merrifield Solid-Phase Method: A technique for automated peptide synthesis where the growing peptide chain is attached to an insoluble polymeric support, allowing for easy purification and washing between coupling steps.

Coupling Reagent: A chemical used to activate the carboxyl group of an amino acid, enabling it to react with the amino group of another amino acid to form a peptide bond.

Amino Acid Activation: The process of converting the carboxyl group of an amino acid into a more reactive species, typically through the use of coupling reagents like DIC, to facilitate peptide bond formation.