Question

Show how each of the following substances can be synthesized starting with the individual amino acids. (a) glycylalanylcysteine (b) \(\mathrm{HO}_{2} \mathrm{C}\left(\mathrm{CH}_{2}\right)_{2} \mathrm{CH}\left(\mathrm{NH}_{2}\right) \mathrm{CONHCH}_{2} \mathrm{CO}_{2} \mathrm{H}\) (c) glutamine from glutamic acid

Short answer

(a) To synthesize glycylalanylcysteine, start with individual amino acids glycine, alanine, and cysteine. Form a peptide bond between glycine and alanine to create glycylalanine, and then form another peptide bond between glycylalanine and cysteine to obtain glycylalanylcysteine. (b) The compound is a dipeptide formed by glycine and β-alanine. To synthesize it, form a peptide bond between glycine and β-alanine, resulting in Glycyl-β-alanine. (c) To synthesize glutamine from glutamic acid, treat glutamic acid with an amidating agent such as ammonia or carbodiimide, converting the carboxyl group in the side chain into an amide group to obtain glutamine.

Step-by-step solution

Starting materials

We need to begin with the individual amino acids: - Glycine: \(\mathrm{NH}_{2}\mathrm{CH}_{2}\mathrm{COOH}\) - Alanine: \(\mathrm{NH}_{2}\mathrm{CH}(\mathrm{CH}_{3})\mathrm{COOH}\) - Cysteine: \(\mathrm{NH}_{2}\mathrm{CH}(\mathrm{CH}_{2}\mathrm{SH})\mathrm{COOH}\)

Peptide bond formation between glycine and alanine

Form a peptide bond between the amine group of glycine and the carboxyl group of alanine, releasing a water molecule in the process: Glycine + Alanine -> Glycylalanine + \(\mathrm{H}_{2}\mathrm{O}\)

Peptide bond formation between glycylalanine and cysteine

Form another peptide bond between the amine group of glycylalanine and the carboxyl group of cysteine, releasing a water molecule in the process: Glycylalanine + Cysteine -> Glycylalanylcysteine + \(\mathrm{H}_{2}\mathrm{O}\) (b) Synthesize the given compound:

Identify the compound and its amino acids

The given formula can be rewritten as: \(\mathrm{NH}_{2}\mathrm{CH}(\mathrm{COOH})\mathrm{CH}_{2}\mathrm{CH}_{2}\mathrm{CO}\mathrm{NH}\mathrm{CH}_{2}\mathrm{COOH}\), which corresponds to a dipeptide formed by glycine and β-alanine. The individual amino acids are: - Glycine: \(\mathrm{NH}_{2}\mathrm{CH}_{2}\mathrm{COOH}\) - β-Alanine: \(\mathrm{NH}_{2}\mathrm{CH}_{2}\mathrm{CH}_{2}\mathrm{COOH}\)

Peptide bond formation between glycine and β-alanine

Form a peptide bond between the amine group of glycine and the carboxyl group of β-alanine, releasing a water molecule in the process: Glycine + β-Alanine -> Glycyl-β-alanine + \(\mathrm{H}_{2}\mathrm{O}\) (c) Synthesize glutamine from glutamic acid:

Identify structural differences

Glutamic acid: \(\mathrm{NH}_{2}\mathrm{CH}(\mathrm{CH}_{2}\mathrm{CH}_{2}\mathrm{COOH})\mathrm{COOH}\) Glutamine: \(\mathrm{NH}_{2}\mathrm{CH}(\mathrm{CH}_{2}\mathrm{CH}_{2}\mathrm{CONH}_{2})\mathrm{COOH}\) The structural difference between them is an amide group (\(\mathrm{NH}_{2}\)) instead of a carboxyl group (\(\mathrm{COOH}\)) in the side chain.

Amide formation

Treat glutamic acid with an amidating agent, such as ammonia or carbodiimide, to convert the carboxyl group into an amide group: Glutamic acid + \(\mathrm{NH}_{3}\) / Carbodiimide -> Glutamine

Key concepts

Amino Acids

Amino acids are the building blocks of proteins and play a crucial role in biology. These compounds consist of a basic amino group (\(\text{NH}_2\)), an acidic carboxyl group (\(\text{COOH}\)), and a distinct side chain that varies among different amino acids.
The side chain determines the characteristics and classification of each amino acid, such as hydrophobic or hydrophilic.
Glycine, alanine, and cysteine, mentioned in the exercise, are examples of amino acids with different side chains.

• Glycine (simplest amino acid): \(\text{NH}_2\text{CH}_2\text{COOH}\)
• Alanine: \(\text{NH}_2\text{CH}(\text{CH}_3)\text{COOH}\)
• Cysteine: \(\text{NH}_2\text{CH}(\text{CH}_2\text{SH})\text{COOH}\)

Amino acids can self-assemble through peptide bonds to form more complex molecules like proteins.

Peptide Bond Formation

A peptide bond is a covalent bond that links amino acids together to form peptides or proteins.
This bond is formed during a chemical reaction between the carboxyl group of one amino acid and the amino group of another, with the elimination of a molecule of water (a condensation reaction).
In the steps given:

• First, glycine forms a peptide bond with alanine to create glycylalanine.
• Next, glycylalanine forms a peptide bond with cysteine to produce glycylalanylcysteine.

This step-by-step process of peptide bond formation ultimately allows the construction of long chains of amino acids like proteins, each with specific sequences and functions.

Amide Formation

Amide formation is a reaction where an amide group (\(\text{CONH}_2\)) is created by replacing a carboxyl group (\(\text{COOH}\)) with an amino group (\(\text{NH}_2\)).
Amides are important in various biological processes, including protein structure.
In the case of converting glutamic acid to glutamine, this involves converting the side chain carboxyl group of glutamic acid into an amide group.
This conversion is essential because glutamine has an amide group where glutamic acid has a carboxyl group.
The synthesis involves using reagents like ammonia or carbodiimide to facilitate this conversion.

Chemical Synthesis Steps

Chemical synthesis of peptides involves a series of precise and sequential reactions.
Each reaction involves step-by-step addition of amino acids, guided by principles of organic chemistry.
Here’s a quick look at how peptide synthesis is accomplished:

• Begin with the selection of specific amino acids required for the target peptide.
• Form peptide bonds via condensation reactions, each resulting in the loss of one molecule of water.
• Each step builds a more complex peptide structure until the target molecule is formed.
• Ensure protective groups are used to prevent unwanted reactions at different functional sites on the amino acids.

Following these meticulous steps ensures that a desired peptide is synthesized correctly, helping in the creation of pharmaceutical drugs and research in biochemical studies.