N-hydroxysuccinimide

Definition

N-hydroxysuccinimide (NHS) is a reactive ester compound commonly used in peptide synthesis. It serves as an efficient coupling agent, facilitating the formation of amide bonds between carboxylic acids and primary amines, a crucial step in the construction of peptide chains.

5 Must Know Facts For Your Next Test

1. N-hydroxysuccinimide is a highly reactive ester that can be used to activate carboxylic acids, making them more susceptible to nucleophilic attack by primary amines.
2. The reaction between a carboxylic acid and N-hydroxysuccinimide produces an NHS ester, which is then able to react with a primary amine to form an amide bond.
3. The NHS ester intermediate is more stable and reactive than the original carboxylic acid, facilitating the coupling reaction and improving the efficiency of peptide synthesis.
4. N-hydroxysuccinimide is often used in conjunction with coupling agents like DCC (dicyclohexylcarbodiimide) or HBTU (O-(Benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate) to further enhance the peptide coupling process.
5. The NHS ester can be selectively displaced by primary amines, allowing for the controlled and stepwise assembly of peptide chains during solid-phase peptide synthesis.

Review Questions

• Explain the role of N-hydroxysuccinimide in the context of peptide synthesis.
  • In peptide synthesis, N-hydroxysuccinimide (NHS) serves as a highly reactive ester that can be used to activate carboxylic acids, making them more susceptible to nucleophilic attack by primary amines. The reaction between a carboxylic acid and NHS produces an NHS ester, which is then able to react with a primary amine to form an amide bond, the crucial linkage in the peptide backbone. The NHS ester intermediate is more stable and reactive than the original carboxylic acid, facilitating the coupling reaction and improving the efficiency of peptide synthesis.
• Describe how N-hydroxysuccinimide is typically used in conjunction with other coupling agents to enhance the peptide coupling process.
  • N-hydroxysuccinimide is often used in combination with other coupling agents, such as DCC (dicyclohexylcarbodiimide) or HBTU (O-(Benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate), to further improve the efficiency of peptide synthesis. These coupling agents work together to activate the carboxylic acid and facilitate the formation of the NHS ester intermediate, which can then selectively react with primary amines to create the amide bonds that make up the peptide chain. The use of these complementary reagents helps to ensure a more controlled and stepwise assembly of the desired peptide sequence.
• Analyze the importance of the selective reactivity of the NHS ester in the context of solid-phase peptide synthesis.
  • The selective reactivity of the NHS ester is crucial in the context of solid-phase peptide synthesis, where the peptide chain is built up step-by-step on a solid support. The NHS ester can be selectively displaced by primary amines, allowing for the controlled and stepwise assembly of the peptide chain. This selective reactivity is essential for ensuring the correct sequence and connectivity of the amino acids, as it prevents unwanted side reactions and enables the precise construction of the desired peptide structure. The ability to selectively react the NHS ester with primary amines is a key feature that makes it an invaluable tool in the efficient and reliable synthesis of peptides and proteins.

Related terms

Peptide Synthesis: The process of chemically assembling amino acids into peptides or proteins, often involving the use of coupling agents like N-hydroxysuccinimide.

Amide Bond: A covalent bond formed between the carboxyl group of one amino acid and the amino group of another, creating the backbone of a peptide or protein.

Carboxylic Acid: An organic compound containing a carbonyl group (C=O) and a hydroxyl group (-OH), which can react with primary amines to form amide bonds.