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PEPTIDE

Head,

Department of Chemistry

Gramin Mahavidyalaya

Vasantnagar(K.)

B. Sc. T. Y.

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Introduction

Peptides are amides obtained by interaction between the amino

and carboxylic groups of two or more amino acid molecules.

Ex. Two molecules of glycine combine to form amide substance

known as glycyl glycine.

The amide group – CO – NH – is called as peptide linkage.

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Classification of peptides

Peptides are classified as under:

Dipeptide: A peptide obtained by the condensation of two amino

acids molecules is called as dipeptide.

Tripeptide: A peptide obtained by the condensation of three

amino acids molecules is called as tripeptide.

Tetrapeptide: A peptide obtained by the condensation of four

amino acids molecules is called as tetrapeptide.

Polypeptide: A peptide obtained by the condensation of more

than four amino acids molecules is called as polypeptide.

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It is observed that the peptides have a free – NH₃⁺ on one end and

free – COO^-group on the other end.

The amino acid having the free – NH₃⁺ group is called as

N – terminal amino acid residue while the amino acid having the

free – COO^-group is called as C – terminal amino acid residue.

In writing the formula of peptides, we start from the left with the

N-terminal amino acid residue and proceed to the right towards

C-terminal amino acid residue.

Peptides of molecular weight upto 10000 are known as

polypeptides whereas peptides of higher molecular weight are the

proteins.

Conventionally, N – terminal amino acid residue is written at the

left end while C – terminal amino acid residue is written at the

right end.

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Nomenclature

While naming a peptide, the names of constituent amino acids are

written from N- terminal (L.H.S.) to C- terminal (R.H.S.).

The suffix “ine” of the names of all amino acids except the

C-terminus acid is replaced by “yl” constituent amino acids.

Sometimes the names of polypeptides are abbreviated by using

three letter abbreviations for constituent amino acids. Ex.

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N-terminus and c-terminus protecting agents

In a peptide the amino acid that contains the free amino group is

called as the N-terminal residue.

It is always written on the left hand side of the polypeptide chain.
The amino acid that contains the free carboxyl group is called as

the C –terminal residue.

It is always written on the right hand side of the polypeptide

chain.

Ex.:- A tripeptide from glycicine, alanine and phenylalanine.

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Synthesis of peptides from amino acids : (di- & tri-)

Synthesis of a peptide from amino acids involves the following steps:

Protection of the – NH₂ group of amino acid with carbobenzoxy chloride (Benzyloxy carbonyl chloride)

Conversion of the carboxyl group into acid chloride.

Formation of peptide linkage.

Removal of chlorobenzoxy group.

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It is observed that condensation of the amino acid molecules does

not take place rapidly.

The carboxy group has to be made reactive in order that the

reaction takes places place with appropriate kinetics.

This can be done by converting amino acid into acid chloride.
But before this done, the amino group of amino acid is protected

with a suitable reagent.

Ordinary acetylation or benzylation is found to be untenable.
Protection is done with carbobenzoxy chloride, which is prepared

as follows:

This group is easy to remove at completion of peptide synthesis.

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This group is easy to remove at completion of peptide synthesis.

Stepwise synthesis of glycylanine (Dipeptide) as:

1. By protecting – NH₂ group (Using carbobenzoxyl chloride)

2. Formation of acid chloride

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Formation of peptide linkage

Removal of protecting group

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By protecting – COOH group (Using benzyl alcohol)

Carboxyl group is generally protected by conversion to methyl,

ethyl, or benzyl esters.

After the peptide formation, methyl and ethyl esters are hydrolysed

to free carboxylic acid.

In case of benzyl esters, catalytic reduction is carried out to obtain

free carboxylic acid.

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Use of DCC (Dicyclohexyl Carbodiimide) as reagent for peptide bond \ formation

The above methods for the peptide bond formation have certain drawbacks.
A serious drawback is that it leads to recimization of the product at the

stereocentre alpha to the acid chloride.

Therefore, attempts were made to discover better methods of peptide bond

formation.

It was found that treatment of a solution of a solution containing an amino

protected amino acid and a carbonyl protected amino acid with diclyclohexyl

carbodiimide (DCC) leads directly to peptide bond formation.

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Peptide bond formation is a dehydration reaction and DCC is a

strong dehydrating agent.

It removes – OH from the carboxyl group of amino acid and – H

from the amino group of the other acid to form a peptide bond

and it itself converted into dicyclohexylurea (DCU).

Removal of protecting groups from the products gives the

dipeptide.