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20CHS03 P.AJITH KUMAR
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8 views27 pages

Vishnu

Uploaded by

20CHS03 P.AJITH KUMAR
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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PEPTIDE SYNTHESIS

VISHNUVARTHA
N.M
23PSC31

1
Introduction :
Peptides are the sequence of amino acids which are formed by the
condensation of two amino acids.
• In which a peptide bond is formed between a carbonyl group of one
amino acid and the amino group of another amino acid.
• Peptides are synthesized in two ways they are
1.solid phase synthesis
2.solution phase synthesis

2
The shortest peptides are dipeptides, consisting of 2 amino acids joined by a
single peptide bond, followed by tripeptide, tetrapeptide, etc.

A polypeptide is a long, continuous, and unbranched peptide chain.

 Hence, peptides fall under the broad chemical classes of biological


oligomers and polymers, alongside nucleic acids, oligosaccharides and
polysaccharides, etc.

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These two groups – N-terminal and the C-terminal residues
respectively.

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Terminal Residue Analysis:

Sanger N – Terminal Analysis

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C-Terminal Analysis:
C- Terminal residues can be identified through the use of digestive
enzymes – Carboxypeptidases

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Peptide Bond Formation:

A key step in the peptide production process is the formation of the peptide
bond. This requires the activation of a carboxylic acid, which is usually
carried out using the peptide coupling reagents.
If the activation of carboxylic acid is slow, the coupling reagents will be
degraded and will no longer be able to activate the carboxyl function.

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Breaking the Peptide into Shorter Chains:
Partial Hydrolysis
Partial hydrolysis can be accomplished either by using dilute acid with a
short reaction time (or) by using enzymes such as Trypsin and Chymotrypsin.

Acid Catalysed cleavage - cleavage at various positions.

Trypsin – Basic amino acid


 Chymotrypsin – Aromatic amino acid

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Peptide Synthesis:

Yield of desired product is low


Difficult to separate

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Benzyloxy carbonyl group (abb.z).

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Tert-butyloxy carbonyl group (abb.Boc.

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Activation of Carboxyl
Group:

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The mixed anhydride can be used to acylate another amino acid and form a
peptide linkage

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Solution Phase Method :

Consider a structure of alanylvalylphenylalanine

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Protect the amino group with z:

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Activate the carbonyl group with ethyl chloroformate

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Form an amide bond to couple the next amino acid

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Solid – Phase Method:
It was discovered by Robert Bruce Merrifield

He synthesized peptide by taking polystyrene solid beads as a support.

The solid support is a special polystyrene bead in which sum of the aromatic
rings have chloromethyl groups.

This polymer, often called the Merrifield Resin, is made by copolymerizing


styrene with a few percent of p – (chloromethyl) styrene.

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Formation of the Merrifield Resin:

Attachment of the C-terminal amino acid:

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Using the tert-Butyloxycarbonyl (Boc.) Protecting Group
The N-protecting group used in the Merrifield procedure is the tert-
butyloxycarbonyl group, abbreviated Boc or 1-Boc. The Boc group is similar to
the Z group, except that it has a tert-butyl group in place of the benzyl group.
Like other tert-butyl esters, the Boc protecting group is easily removed under
acidic conditions. The acid chloride of the Boc group is unstable, so we use the
anhydride, di-tert-butyldicarbonate, to attach the group to the amino acid

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Use of DCC as a Peptide
Coupling Agent
The final reaction needed for the Merrifield procedure is the peptide bond-forming
condensation. When a mixture of an amine and an acid is treated with N,N’-
dicyclohexylcarbodiamide (abbreviated DCC), the amine and the acid couple to form
an amide. The molecule of water lost in this condensation converts DCC to N,N’-
dicyclohexylurea (DCU)

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Synthesis of Tripeptide using
Merrifield Solid – Peptide Synthesis:

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Step: 1 Deprotection

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Step: 2 Coupling

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Use trifluoroacetic acid to deprotect the amino group at the end of the growing
chain.
And the next Boc-amino acid, using DCC as a coupling agent

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Reference:

Organic Chemistry, 8th Edition, L. G. Wade Jr.

Organic Chemistry, 10th Edition, T.W. Graham Solomons, Craig B.


Fryhle.

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Thank you

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