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Peptides and proteins are polymers of amino acids linked together by amide bonds

Amino Acids

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Aliphatic Side-Chain Amino Acids

+H3N CH C

H

O-

O

+H3N CH C

CH3

O-

O

glycine alanine proline

+H 3N CH C

CH

O-

O

CH 3

CH 3

+H 3N CH C

CH 2

O-

O

CH CH 3

CH 3

+H 3N CH C

CH

O-

O

CH 3

CH 2

CH 3

valine

leucineisoleucine

Hydroxy-Containing Amino Acids

+H 3N CH C

CH

O-

O

OH

CH 3

+H 3N CH C

CH 2

O-

O

OH

serine threonine

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2 stereocenters

2 stereocenters

2

Sulfur-Containing Amino Acids

+H 3N CH C

CH 2

O-

O

SH

+H 3N CH C

CH 2

O-

O

CH 2

S

CH 3

cysteinemethionine

Acidic Amino Acids

+H3N CH C

CH2

O-

O

C

O-

O

+H3N CH C

CH2

O-

O

CH2

C

O-

O

aspartatic acidglutamic acid

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Amides of Acidic Amino Acids +H3N CH C

CH2

O-

O

CH2

C

NH2

O

+H3N CH C

CH2

O-

O

C

NH2

O

asparagine glutamine

Basic Amino Acids

+H3N CH C

CH2

O-

O

CH2

CH2

CH2

NH3+

+H3N CH C

CH2

O-

O

CH2

CH2

NH

C

NH2

NH2+

lysine arginine

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Benzene-Containing Amino Acids +H3N CH C

CH2

O-

O

+H3N CH C

CH2

O-

O

OH

phenylalanine tyrosine

+H2N

C O-

O

+H3N CH C

CH2

O-

O

N

NH

+H3N CH C

CH2

O-

O

HN

proline histidine tryptophan

Heterocyclic Amino Acids

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Configuration of Amino Acids

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Acid–Base Properties of Amino Acids

An amino acid can never exist as an uncharged compound

The isoelectric point (pI) of an amino acid is the pH atwhich it has no net charge

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Some amino acids have ionizable hydrogens on their side chains

The pI of an amino acid that has an ionizable side chain is the average of the pKavalues of the similarly ionizing groups

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A mixture of amino acids can be separated by electrophoresis on the basis of their pI values

A mixture of amino acids can also be separated on the basis of polarity

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Ninhydrin is used to detect the individual amino acids

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Synthesis

Gabriel synthesiswith phtalimide

Malonic synthesis + Gabriel reaction

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Strecker Reaction

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Enzymatic synthesisNon chiral 2-oxopentanedioic gives optically pure glutamic acid

Resolution of racemic mixtures

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Formation of a Peptide

Peptide Bond

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Formation of Disulfide Bonds

Disulfides can be reduced to thiols

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Angiotensin II: blood pressure regulating hormone

Asp-Arg-Val-Tyr-Ile-His-Pro-Phe

Vasopressin: diuretichormone

Peptides

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inhibitory neurotransmitter

excitatory neurotransmitter

Tyroid hormones

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Vancomycin is a very large, aminoglycoside antibiotic produced by the

fermentation of the actinomycete bacteria Amycolatopsis orientalis. The main

target of this antibiotic is the D-alanyl-D-alanine terminal dipeptide of

peptidoglycan precursors, used by bacteria for constructing their cell walls.

Vancomycin binds with the substrate, not the enzyme: this is in contrast to the

way penicillin inhibits peptidoglycan synthesis.

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Antibiotic peptides

The disulfide bridge in proteins contributes to the overall shape of a protein

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Opioid peptides

Peptide hormones

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A problem arises when one attempts to make a particular peptide

Strategy for making a specific peptide: Gly-Ala

and ot Ala-Gly, Ala-Ala, etc

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Protection of N-terminus

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+

12

Activation of COOH terminus

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Protecting group removalGentilucci, Amino Acids, Peptides, and Proteins

Merrifieldautomated SPPS

Etc, etc

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Determination of protein sequence

1. Cleavage and identification of disulfide bridges

2. Acidic hydrolysis and identification of a.a. composition

protein

6 N HCl

100°C24 h

amino acids

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3. Determination N-terminal amino acid by Edman degradation

The particular PTH-amino acid can be identified by chromatography using known standards

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5. The C-terminal amino acid can be identified by treating the protein with peptidases (eg carboxypeptidases)

4. Cyanogen bromide causes the hydrolysis of the amide bond on the C-side of a methionine residue

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Secondary structure

Describe the conformation of segments of the backbone chain of a peptide or

protein

Three factors determine the choice of secondary structure:

the regional planarity about each peptide bond

maximization of the number of peptide groups that engage in hydrogen bonding

adequate separation between nearby R groups

Proteins

The tertiary structure

It is defined by the primary structure

The stabilizing interactions include covalent bonds, hydrogen bonds, electrostatic

attractions, and hydrophobic interactions

Disulfide bonds are the only covalent bonds that can form when a protein folds

Proteins that have more than one peptide chain are called oligomers

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(prolines are helix breakers)

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The α-Helix Is Stabilized by Hydrogen Bonds

Two Types of β-Pleated Sheets

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The tertiary structure is the three-dimensional arrangement of all the atoms in the protein

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Most globular proteins have coil conformations

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