Linker

Definition

A linker is a chemical compound used in organic synthesis, particularly in the context of peptide synthesis, to covalently attach a molecule of interest to a solid support or resin. Linkers serve as the bridge between the growing peptide chain and the solid phase, enabling the automated, step-wise construction of peptides using the Merrifield solid-phase method.

5 Must Know Facts For Your Next Test

1. Linkers in SPPS provide a covalent attachment point between the growing peptide chain and the solid support, enabling the use of excess reagents to drive the reactions to completion.
2. The choice of linker is crucial as it must be stable under the reaction conditions used in peptide synthesis, yet labile enough to allow for the final cleavage of the peptide from the solid support.
3. Commonly used linkers in SPPS include Wang resin, Rink amide resin, and Trityl resins, each with their own unique properties and cleavage conditions.
4. Linkers can also be designed to introduce specific functionalities or tags, such as fluorescent dyes or affinity tags, to the synthesized peptide for downstream applications.
5. The loading capacity of the linker, measured in mmol/g, is an important consideration as it determines the maximum amount of peptide that can be synthesized on a given mass of resin.

Review Questions

• Explain the role of the linker in the Merrifield solid-phase method of peptide synthesis.
  • The linker plays a crucial role in the Merrifield solid-phase method of peptide synthesis. It serves as the covalent attachment point between the growing peptide chain and the solid support, typically a resin bead. The linker allows for the automated, step-wise addition of amino acids to build the desired peptide sequence, as the excess reagents used in each coupling and deprotection step can be easily removed by washing the resin. The choice of linker is critical, as it must be stable under the reaction conditions yet labile enough to allow for the final cleavage of the peptide from the solid support.
• Describe how the properties of the linker can be tailored to suit specific applications in peptide synthesis.
  • Linkers used in solid-phase peptide synthesis can be designed to introduce specific functionalities or tags to the synthesized peptide. For example, linkers with fluorescent dyes or affinity tags can be employed to enable the detection or purification of the final peptide product. Additionally, the loading capacity of the linker, measured in mmol/g, is an important consideration as it determines the maximum amount of peptide that can be synthesized on a given mass of resin. The choice of linker can also influence the cleavage conditions, with some linkers being more labile than others, allowing for the selective release of the peptide from the solid support.
• Evaluate the importance of the linker in the overall success and efficiency of the Merrifield solid-phase method of peptide synthesis.
  • The linker is a critical component in the Merrifield solid-phase method of peptide synthesis, as it directly impacts the efficiency and success of the automated, step-wise construction of peptides. The linker serves as the bridge between the growing peptide chain and the solid support, enabling the use of excess reagents to drive the reactions to completion and facilitating the easy removal of byproducts and unreacted species. The choice of linker must be carefully considered, as it needs to be stable under the reaction conditions yet labile enough to allow for the final cleavage of the peptide. Additionally, the linker's properties, such as loading capacity and the ability to introduce specific functionalities, can be tailored to suit the requirements of the particular peptide synthesis. Overall, the linker is a fundamental element that enables the Merrifield solid-phase method to be a powerful and versatile technique for the automated synthesis of peptides.

Related terms

Solid-Phase Peptide Synthesis (SPPS): A technique for the automated, step-wise synthesis of peptides where the growing peptide chain is attached to a solid support, such as a resin bead, through a linker.

Merrifield Solid-Phase Method: An automated peptide synthesis technique developed by Bruce Merrifield, which utilizes a linker to attach the first amino acid to a solid support, allowing for the stepwise addition of amino acids to build the desired peptide sequence.

Fmoc Protecting Group: A commonly used protecting group in SPPS that is attached to the N-terminus of the amino acids, allowing for selective deprotection and coupling of the next amino acid in the sequence.