SN2 SHORT NOTE 5M ★ High-yield

Describe the peptide bond with its characteristics and significance.

Biochemistry · 1st Professional — Pre-Clinical

Definition

Peptide bond = the covalent amide linkage formed between the α-carboxyl group of one amino acid and the α-amino group of the next, with the elimination of a molecule of water.

Formation

R1–CH(NH2)–COOH + H2N–CH(R2)–COOH → Condensation — loss of H2O → R1–CH(NH2)–CO–NH–CH(R2)–COOH → dipeptide

In the cell it is formed on the ribosome by peptidyl transferase, which is a ribozyme
It is thermodynamically unfavourable and requires energy — 4 high-energy bonds per peptide bond

Characteristics

Property	Explanation
Partial double bond character	Resonance between the C=O and C–N bonds; the C–N bond is shorter than a normal single bond
Rigid and planar	No free rotation about the C–N bond; six atoms lie in one plane
Trans configuration	The two α-carbons lie on opposite sides — less steric hindrance. Except before proline, where cis also occurs
Uncharged but polar	Participates in hydrogen bonding — the basis of secondary structure
Strong and stable	Resists spontaneous hydrolysis; needs enzymes, strong acid or prolonged heat
Rotation permitted at φ and ψ	The bonds either side of the α-carbon; permitted angles shown on the Ramachandran plot

Significance

The rigidity and planarity restrict the shapes a chain can adopt, which is precisely what makes reproducible folding possible
Its hydrogen bonding capacity generates the α-helix and β-pleated sheet
It is not broken by denaturation — which is why primary structure survives when a protein is denatured

Cleavage of Peptide Bonds

Method	Agent	Specificity
Enzymatic — endopeptidase	Trypsin	C-side of lysine and arginine
—	Chymotrypsin	C-side of aromatic amino acids
—	Pepsin	N-side of aromatic amino acids
Enzymatic — exopeptidase	Carboxypeptidase; aminopeptidase	From the C- or N-terminal end
Chemical	Cyanogen bromide	C-side of methionine
—	6 N HCl at 110 °C for 24 h	Complete hydrolysis; destroys tryptophan

Applied Aspects

Biuret reaction detects two or more peptide bonds — a violet colour with copper in alkali; the standard method of protein estimation. Free amino acids and dipeptides give no colour
Protein sequencing uses specific cleavage with overlapping fragments; Edman degradation removes one residue at a time from the N-terminus
ACE inhibitors and protease inhibitors act by blocking peptide bond cleavage — the basis of captopril in hypertension and of the antiretroviral protease inhibitors
Penicillin inhibits bacterial transpeptidase, preventing cross-linking of peptidoglycan — peptide bond chemistry exploited for selective toxicity

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