THE CHEMISTRY OF PEPTIDES THE DIFFICULT TO COLLECT DATA FOR READERS , THREFORE HERE WE HAVE COLLECTED ALL THE DATA AT A PLACE AND PROVIDED EASIER TO CHEMISTRIANS.

1. Chemistry of Peptide

2. Content
• Introduction
• Peptide Bond Formation
• Coupling reagents used in Peptide Synthesis
• Carbodiimides
• Phosphonium and aminium salts
• Fluoroformamidinium coupling reagents
• Organophosphorus reagent
• References
2

3. Introduction
• Amino acids are organic compounds containing amine (-NH2) and
carboxyl (-COOH) functional groups, along with a side chain (R group)
specific to each amino acid. The key elements of an amino acid are
carbon (C), hydrogen (H), oxygen (O), and nitrogen (N),
• About 500 naturally occurring amino acids are known (though only 20
appear in the genetic code) and can be classified in many ways.
• They can be classified according to the core structural functional
groups' locations as alpha-(α-), beta- (β-), gamma- (γ-) or delta- (δ-)
amino acids; other categories relate to polarity, pH level, and side
chain group type (aliphatic, acyclic, aromatic, containing hydroxyl or
sulfur, etc.).
3

4. • The covalent chemical bonds are formed when the carboxyl group of
one amino acid reacts with the amino group of another.
• 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.
4

5. 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.
5

6. Coupling Reagents Used in Peptide Synthesis
The coupling reaction in which coupling reagents are used in
the peptide bond formation in peptide synthesis.The coupling reagents
are
• Carbodiimides
• Phosphonium and aminium salts
• Fluoroformamidinium coupling reagents
• Organophosphorus reagents
• Triazine coupling reagents
6

7. Dicyclohexyl carbodiimide (DCC) and diisopropyl carbodiimide (DIC) are
commonly used to prepare amides, esters and acid anhydrides from carboxylic
acid.
1. Carbodiimides
7
EDC -1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide
CIC- N-cyclohexyl-N-isopropylcarbodiimide,
DCC -N,N0-dicyclohexylcarbodiimide

8. 2. Phosphonium and aminium salts
• The use of phosphonium salts as coupling reagents such as, (benzotriazol-1-yloxy)tris
(dimethylamino) phosphonium hexafluorophosphate (BOP) and (benzotriazol-1-
yloxy)tris (pyrrolidino) phosphonium hexafluorophosphate (PyBOP,).
• The BOP reagent has been used in many syntheses since it is easy to use and
promotes rapid coupling. However, it produces hexamethylphosphorotriamide
(HMPA) as a side by-product, which has been classified as a potential human
carcinogenic.
• Phosphonium salts derived from HOAt, such as (7-azabenzotriazol- 1-yloxy)tris(di-
methylamino)phosphonium hexafluorophosphate (AOP) and (7-azabenzotriazol-1-
yloxy)tris (pyrrolidino) phosphonium hexafluorophosphate (PyAOP)have also been
prepared and are generally more efficient than BOP and PyBOP as coupling reagents.
8

9. 9

10. 3. Uronium salts
The uranium salt N-[(1H-benzotriazol-1-yl)(dimethylamino)methylene]-N-methyl
methanaminium hexafluorophosphate N-oxide (N-HBTU 51), N-[(dimethylamino)-1H-
1,2,3-triazolo[4,5-b]pyridin-1-ylmethylene]-N-methyl methanaminium
hexafluorophosphate N-oxide (N-HATU, 52), and 1-(1-pyrrolidinyl-1H-1,2,3-
triazolo[4,5-b]pyridin-1-yl-methylene) pyrrolidinmium hexafluorophosphate N-oxide
(HAPyU, 53) crystallize as aminium salts ( guanidinium N-oxides) rather than the
corresponding uronium salts (49 and 50).
10

11. 4.Fluoroformamidinium coupling reagents
• Among the most reactive of the common coupling reagents are the
preformed amino acid fluorides.
• The amidinium reagents are 1,1,3,3-tetramethyl fluoroformamidinium
hexafluorophosphate (TFFH, 77), bis (tetramethylene) fluoroformamidinium
hexafluorophosphate (BTFFH, 78) and 1,3-dimethyl-2-fluoro-4,5-dihydro-1H-
imidazolium hexafluorophosphate (DFIH,79) these reagent used in peptide
synthesis.
11

12. 5.Organophosphorus reagents
The Organophosphorus reagents are diphenyl phosphorochloridate and These
reagents are crystalline and stable for long-term storage.
Diphenyl
phosphoryl
azide
DECP-Diethyl chlorophosphite MPTA- α-Methoxy-α-Trifluoromethylphenylacetic acid
DEPB- Diethyl(3-pyridyl)borane MPTO- 3-Dimethylphosphinothioyl-2(3H)-oxazolone
DEPC- Diethyl pyrocarbonate
12

13. THANK YOU
13