Organic Chemistry 4th Edition

Paula Yurkanis Bruice

Chapter 23

Amino Acids,Peptides,

and Proteins

Irene LeeCase Western Reserve

UniversityCleveland, OH

©2004, Prentice Hall

Peptides and proteins are polymers of amino acids linkedtogether by amide bonds

Aliphatic Side-Chain Amino Acids

+H3N CH C

H

O-

O

+H3N CH C

CH3

O-

O

+H3N CH C

CH

O-

O

CH3

CH3

+H3N CH C

CH2

O-

O

CH CH3

CH3

+H3N CH C

CH

O-

O

CH3

CH2

CH3

glycine alanine

valine leucine isoleucine

Hydroxy-Containing Amino Acids

Sulfur-Containing Amino Acids

+H3N CH C

CH

O-

O

OH

CH3

+H3N CH C

CH2

O-

O

OH

serine threonine

+H3N CH C

CH2

O-

O

SH

+H3N CH C

CH2

O-

O

CH2

S

CH3cysteine methionine

Acidic Amino Acids

Amides of Acidic Amino Acids

+H3N CH C

CH2

O-

O

C

O-

O

+H3N CH C

CH2

O-

O

CH2

C

O-

Oaspartatic acid glutamic acid

+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

Benzene-Containing Amino Acids

+H3N CH C

CH2

O-

O

+H3N CH C

CH2

O-

O

OH

phenylalanine tyrosine

Heterocyclic Amino Acids

+H2N

C O-

O

+H3N CH C

CH2

O-

O

N

NH

+H3N CH C

CH2

O-

O

HN

proline histidine tryptophan

Configuration of Amino Acids

Acid–Base Properties of Amino Acids

An amino acid can never exist as an uncharged compound

Some amino acids have ionizable hydrogens on their side chains

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

The pI of an amino acid that has an ionizable side chainis the average of the pKa values of the similarly ionizing groups

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

Ninhydrin is used to detect the individual amino acids

A mixture of amino acids can also be separated on thebasis of polarity

Ion-exchange chromatography can be used to performpreparative separation of amino acids

Negatively charged resin binds selectively to positivelycharged amino acids

• Cations bind most strongly to cation-exchange resins

• Anions bind most strongly to anion-exchange resins

• An amino acid analyzer is an instrument that automates ion-exchange chromatography

Ion-Exchange Chromatography

Resolution of Racemic Mixtures of Amino Acids

Formation of a Peptide

Peptide Bond

Formation of Disulfide Bonds

Disulfides can be reduced to thiols

The disulfide bridge in proteins contributes to the overallshape of a protein

Because amino acids have two functional groups, a problem arises when one attempts to make a particular peptide

Strategy for Making a Specific Peptide Bond

Amino acids can be added to the growing C-terminal endby repeating these two steps

When the desired number of amino acids has been added to the chain, the protecting group can be removed

An Improved Peptide Synthesis Strategy

The first step in determining the sequence of amino acidsin a peptide or protein is to cleave the disulfide bridges

The next step is to determine the number and kinds of amino acids in the peptide or protein

protein amino acids6 N HCl

100°C24 h

The N-terminal amino acid of a peptide or a protein canalso be determined by Edman degradation

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

The C-terminal amino acid can be identified by treating the protein with carboxypeptidase

Cyanogen bromide causes the hydrolysis of the amidebond on the C-side of a methionine residue

Secondary Structure of Proteins

Describe the conformation of segments of the backbonechain of a peptide or protein

Three factors determine the choice of secondarystructure:

• 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

The -Helix Is Stabilized by Hydrogen Bonds

Prolines are helix breakers

Two Types of -Pleated Sheets

Most globular proteins have coil conformations

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

The stabilizing interactions include covalent bonds, hydrogen bonds, electrostatic attractions, and hydrophobic interactions

The tertiary structure is defined by the primary structure

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

Proteins that have more than one peptide chain arecalled oligomers