Latest revision as of 14:18, 21 February 2025

Peptide Synthesis[edit]

Peptide synthesis is the process of creating peptides, which are short chains of amino acids linked by peptide bonds. This process is fundamental in the field of biochemistry and molecular biology, as peptides play crucial roles in biological functions and are used in research and therapeutic applications.

Methods of Peptide Synthesis[edit]

Peptide synthesis can be performed using various methods, each with its own advantages and limitations. The two primary methods are liquid-phase peptide synthesis and solid-phase peptide synthesis.

Liquid-Phase Peptide Synthesis[edit]

Liquid-phase peptide synthesis involves the sequential addition of amino acids in solution. This method was historically significant but has largely been replaced by solid-phase techniques due to the latter's efficiency and ease of purification.

Solid-Phase Peptide Synthesis[edit]

Solid-phase peptide synthesis (SPPS) is the most common method used today. It involves anchoring the C-terminal amino acid of the peptide to an insoluble resin, allowing for the sequential addition of protected amino acids. This method was pioneered by Robert Bruce Merrifield, who was awarded the Nobel Prize in Chemistry in 1984 for this innovation.

Coupling Reagents[edit]

The formation of peptide bonds requires activation of the carboxyl group of the incoming amino acid. Various coupling reagents are used to facilitate this process.

Carbodiimide Reagents[edit]

Carbodiimides, such as dicyclohexylcarbodiimide (DCC) and diisopropylcarbodiimide (DIC), are commonly used in peptide synthesis. They activate the carboxyl group to form an active ester, which then reacts with the amine group of the next amino acid.

Additives[edit]

Additives such as 1-hydroxybenzotriazole (HOBt) and 1-hydroxy-7-azabenzotriazole (HOAt) are often used to suppress racemization and improve yields.

Protecting Groups[edit]

Protecting groups are essential in peptide synthesis to prevent unwanted side reactions. The most common protecting groups are used for the N-terminus and side chains of amino acids.

N-Terminus Protecting Groups[edit]

Cbz protecting group for N-terminus.

The carbobenzyloxy (Cbz), tert-butyloxycarbonyl (Boc), and 9-fluorenylmethyloxycarbonyl (Fmoc) groups are commonly used to protect the N-terminus of amino acids.

Side Chain Protecting Groups[edit]

Side chain protecting groups are used to protect functional groups on the amino acid side chains that might react during peptide synthesis.

Deprotection[edit]

After the peptide chain is assembled, the protecting groups must be removed to yield the final peptide.

Boc Deprotection[edit]

Boc deprotection mechanism.

Boc groups are removed using strong acids such as trifluoroacetic acid (TFA).

Fmoc Deprotection[edit]

Fmoc groups are removed using mild bases such as piperidine.

Related Pages[edit]

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-{{Short description|Overview of peptide synthesis in biochemistry}}
+= Peptide Synthesis =
-'''Peptide synthesis''' is a process in [[biochemistry]] that involves the creation of [[peptides]], which are short chains of [[amino acids]] linked by [[peptide bonds]]. This process is fundamental in the study of [[proteins]] and [[enzymes]], as peptides serve as the building blocks of these larger molecules. Peptide synthesis can be performed using various methods, each with its own advantages and applications.
+[[File:Peptide_coupling.svg|thumb|right|300px|General scheme of peptide coupling.]]
-==Methods of Peptide Synthesis==
+'''Peptide synthesis''' is the process of creating [[peptides]], which are short chains of [[amino acids]] linked by [[peptide bonds]]. This process is fundamental in the field of [[biochemistry]] and [[molecular biology]], as peptides play crucial roles in biological functions and are used in research and therapeutic applications.
-Peptide synthesis can be broadly categorized into two main types: [[solid-phase peptide synthesis]] (SPPS) and [[liquid-phase peptide synthesis]].
+== Methods of Peptide Synthesis ==
-===Solid-Phase Peptide Synthesis (SPPS)===
+Peptide synthesis can be performed using various methods, each with its own advantages and limitations. The two primary methods are [[liquid-phase peptide synthesis]] and [[solid-phase peptide synthesis]].
-[[File:Peptide_synthesis.png|thumb|right|Diagram of solid-phase peptide synthesis.]]
-SPPS is the most commonly used method for synthesizing peptides. It was developed by [[Robert Bruce Merrifield]] in 1963 and revolutionized the field of peptide chemistry. In SPPS, the peptide is assembled on a solid support, typically a resin, which simplifies the purification process. The synthesis proceeds through a series of cycles, each involving the addition of a single amino acid residue.
-The key steps in SPPS include:
+=== Liquid-Phase Peptide Synthesis ===
-* '''Deprotection''': Removal of the protecting group from the amino group of the growing peptide chain.
-* '''Coupling''': Addition of the next amino acid, which is activated to form a peptide bond with the free amino group.
-* '''Cleavage''': Once the peptide chain is complete, it is cleaved from the resin and further purified.
-===Liquid-Phase Peptide Synthesis===
+Liquid-phase peptide synthesis involves the sequential addition of amino acids in solution. This method was historically significant but has largely been replaced by solid-phase techniques due to the latter's efficiency and ease of purification.
-Liquid-phase peptide synthesis is an older method that involves the sequential addition of amino acids in solution. While it is less commonly used today due to the complexity of purification, it is still valuable for synthesizing very short peptides or when specific modifications are required.
-==Applications of Peptide Synthesis==
+=== Solid-Phase Peptide Synthesis ===
-Peptide synthesis is crucial in various fields of research and medicine. Some of the key applications include:
-* '''Drug Development''': Peptides are used as therapeutic agents in the treatment of diseases such as [[cancer]], [[diabetes]], and [[infectious diseases]].
+[[File:Solid_Phase_Peptide_Synthesis.jpg|thumb|left|300px|Solid-phase peptide synthesis apparatus.]]
-* '''Vaccine Development''': Synthetic peptides are used to develop vaccines by mimicking [[antigenic determinants]] of pathogens.
-* '''Biochemical Research''': Peptides are used as tools to study protein-protein interactions, enzyme activity, and [[signal transduction]] pathways.
-==Challenges in Peptide Synthesis==
+Solid-phase peptide synthesis (SPPS) is the most common method used today. It involves anchoring the C-terminal amino acid of the peptide to an insoluble resin, allowing for the sequential addition of protected amino acids. This method was pioneered by [[Robert Bruce Merrifield]], who was awarded the [[Nobel Prize in Chemistry]] in 1984 for this innovation.
-Despite its widespread use, peptide synthesis presents several challenges:
-* '''Racemization''': The formation of [[D-amino acids]] during synthesis can lead to racemization, affecting the biological activity of the peptide.
+== Coupling Reagents ==
-* '''Aggregation''': Peptides can aggregate during synthesis, leading to incomplete reactions and low yields.
-* '''Purification''': The purification of synthetic peptides can be difficult, especially for long sequences or those with hydrophobic residues.
-==Related Pages==
+The formation of peptide bonds requires activation of the carboxyl group of the incoming amino acid. Various coupling reagents are used to facilitate this process.
+=== Carbodiimide Reagents ===
+[[File:DIC_HOBt_coupling.svg|thumb|right|300px|DIC/HOBt coupling mechanism.]]
+Carbodiimides, such as [[dicyclohexylcarbodiimide]] (DCC) and [[diisopropylcarbodiimide]] (DIC), are commonly used in peptide synthesis. They activate the carboxyl group to form an active ester, which then reacts with the amine group of the next amino acid.
+=== Additives ===
+[[File:HOBT.png|thumb|left|150px|Structure of HOBt.]]
+Additives such as [[1-hydroxybenzotriazole]] (HOBt) and [[1-hydroxy-7-azabenzotriazole]] (HOAt) are often used to suppress racemization and improve yields.
+[[File:1-hydroxy-7-aza-benzotriazole.svg|thumb|right|150px|Structure of HOAt.]]
+== Protecting Groups ==
+Protecting groups are essential in peptide synthesis to prevent unwanted side reactions. The most common protecting groups are used for the N-terminus and side chains of amino acids.
+=== N-Terminus Protecting Groups ===
+[[File:Cbz_to_protect_N-terminus.svg|thumb|left|300px|Cbz protecting group for N-terminus.]]
+The [[carbobenzyloxy]] (Cbz), [[tert-butyloxycarbonyl]] (Boc), and [[9-fluorenylmethyloxycarbonyl]] (Fmoc) groups are commonly used to protect the N-terminus of amino acids.
+=== Side Chain Protecting Groups ===
+Side chain protecting groups are used to protect functional groups on the amino acid side chains that might react during peptide synthesis.
+== Deprotection ==
+After the peptide chain is assembled, the protecting groups must be removed to yield the final peptide.
+=== Boc Deprotection ===
+[[File:Boc_deprotection_peptide.svg|thumb|right|300px|Boc deprotection mechanism.]]
+Boc groups are removed using strong acids such as [[trifluoroacetic acid]] (TFA).
+=== Fmoc Deprotection ===
+[[File:Fmoc-PG_Cleavage.png|thumb|left|300px|Fmoc deprotection mechanism.]]
+Fmoc groups are removed using mild bases such as [[piperidine]].
+== Related Pages ==
 * [[Amino acid synthesis]]
-* [[Protein synthesis]]
+* [[Protein biosynthesis]]
-* [[Enzyme]]
 * [[Biochemistry]]
-[[Category:Biochemistry]]
+[[Category:Peptide synthesis]]
-[[Category:Peptides]]
-[[Category:Synthetic biology]]

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