Mary K.

Campbell
Shawn O. Farrell
http://academic.cengage.com/chemistry/campbell

Chapter Three
Amino Acids and Peptides

Paul D. Adams University of Arkansas

Amino Acids
• Amino acid: a compound that contains
both an amino group and a carboxyl
group
• -Amino acid has an amino group
attached to the carbon adjacent to
the carboxyl group
• -carbon also bound to side chain
group, R
• R gives identity to amino acid
• Two steroisomers of amino acids
are designated L- or D-. Based on
similarity to glyceraldehdye
(Figure 3.2)
Amino Acid Structure and Properties
• With the exception of glycine, all protein-derived
amino acids have at least one stereocenter (the -
carbon) and are chiral (stereoisomers)
• the vast majority of -amino acids have the L-
configuration at the -carbon (Proline is usually D)
• Side-chain carbons in other amino acids designated
with Greek symbols, starting at a carbon (…etc)
• Amino acids can be referred to by three-letter or one-
letter codes. Table 3.1 (KNOW THESE)
Individual Amino Acids
• Group A: Nonpolar side chains- Ala, Val, Leu, Ile, Pro.
Phe, Trp, Met.
• Ala, Val, Leu, Ile, Pro- contain aliphatic hydrocarbon
group. Pro has cyclic structure.
• Phe- hydrocarbon aromatic ring.
• Trp- Indole ring side chain, aromatic.
• Met- Sulfur atom in side chain.
Amino Acids (cont’d)
• Group B: Neutral Polar side chains- Ser, Thr, Tyr,
Cys, Glu, Asn

• Ser, Thr- Side chain is polar hydroxyl group

• Tyr- hydroxyl group bonded to aromatic hydrocarbon

group

• Cys- Side chain contains thiol group (-SH)

• Gln, Asn- contain amide bonds in side chain

Amino Acids (cont’d)
• Group C: Acidic Side Chains: Glu, Asp

• Both have a carboxyl group in side chain

• Can lose a proton, forming a carboxylate ion

• These amino acids are negatively charged at neutral

pH
Amino Acids (cont’d)
• Group D: Basic side chains: His, Lys, Arg

• Side chains are positively charged at pH 7

• Arg-side chain is a guanidino group

• His-side chain is an imidazole group

• Lys-side chain NH3 group is attached to an aliphatic

hydrocarbon chain
Amino acid summary
Important structural features:

1. All 20 are -amino acids

2. For 19 of the 20, the -amino group is primary; for proline,

it is secondary

3. With the exception of glycine, the -carbon of each is a

stereocenter

4. Isoleucine and threonine contain a second stereocenter

5. 3, and 1-letter codes in Table 3.1.

Uncommon Amino Acids
• Each derived from
a common amino
acid by a
modification
• hydroxylysine and
hydroxyproline are
found only in a
few connective
tissues
such as collagen
• thyroxine is found
only in the thyroid
gland
Ionization of Amino Acids
• In amino acid, carboxyl group (-) and amino group (+) are
charged at neutral pH.
• In free amino acids -carboxyl, and a-amino groups have
titratable protons. Some side chains do as well
Ionization of Amino Acids
• Remember, amino acids without charged groups on side chain
exist in neutral solution as zwitterions with no net charge
Titration of Amino Acids
• When an amino acid is titrated, the titration curve represents the reaction of
each functional group with the hydroxide ion
Titration of alanine with NaOH
Titration of histidine with NaOH
Acidity: -COOH Groups
• The average pKa of an -carboxyl group is 2.19,
which makes them considerably stronger acids than
acetic acid (pKa 4.76)
• the greater acidity of the amino acid carboxyl group is
due to the electron-withdrawing inductive effect of the -
NH3+ group
Basicity: -NH3+ groups
• The average value of pKa for an -NH3+ group is
9.47, compared with a value of 10.76 for a 2°
alkylammonium ion
Basicity (cont’d)
Guanidine Group
• The side chain of arginine is a considerably stronger
base than an aliphatic amine
• basicity of the guanido group is attributed to the large
resonance stabilization of the protonated form relative
to the neutral form

Imidazole Group
• The side chain imidazole group of histidine is a
heterocyclic aromatic amine
Ionization vs pH
• Given the value of pKa of each functional group, we
can calculate the ratio of each acid to its conjugate
base as a function of pH
• Consider the ionization of an -COOH
pK a = 2.00
-
COOH + H2 O COO + H3 O +

• writing the acid ionization constant and rearranging

terms gives (remember Ch. 2)

[ H 3 O+ ] [ -COO - ] [ -COO - ] Ka
Ka = or =
[ -COO H] [ -COO H] [ H 3 O+ ]
Ionization vs pH (cont’d)
• substituting the value of Ka (1 x 10-2) for the hydrogen
ion concentration at pH 7.0 (1.0 x 10-7) gives

[ -COO - ] Ka 1.00 x 10-2

= = = 1.00 x 105
[ -COO H] [ H 3 O+ ] 1.00 x 10-7

• at pH 7.0, the -carboxyl group is virtually 100% in

the ionized or conjugate base form, and has a net
charge of -1
• we can repeat this calculation at any pH and
determine the ratio of [-COO-] to [-COOH] and the
net charge on the -carboxyl at that pH
Ionization vs pH (cont’d)
• We can also calculate the ratio of acid to conjugate
base for an -NH3+ group; for this calculation,
assume a value 10.0 for pKa

+ pK a = 10.00
NH3 + H2 O NH2 + H3 O +

• writing the acid ionization constant and rearranging

gives [ -NH ] 2 Ka
=
[ -NH 3 + ] [H 3 O+ ]
Ionization vs pH

• substituting values for Ka of an -NH3+ group and

the hydrogen ion concentration at pH 7.0 gives

[ -NH 2 ] Ka 1.00 x 10-10

= + = = 1.00 x 10-3
[ -NH 3 ]
+ [H 3 O ] 1.00 x 10-7

• at pH 7.0, the ratio of -NH2 to -NH3 + is

approximately 1 to 1000
• at this pH, an -amino group is 99.9% in the acid
or protonated form and has a charge of +1
Henderson-Hasselbalch Equation
• We have calculated the ratio of acid to conjugate
base for an -carboxyl group and an -amino group
at pH 7.0
• We can do this for any weak acid and its conjugate
base at any pH using the Henderson-Hasselbalch
equation (Ch. 2)

[conjugate base]
pH = pK a + log
[weak acid]
Isoelectric pH
• Isoelectric pH, pI: the pH at which the majority of molecules
of a compound in solution have no net charge

• the pI for glycine, for example, falls midway between the pKa
values for the carboxyl and amino groups

pI = 1 ( p Ka COOH + p Ka N H3 + )
2

= 1 (2.35 + 9.78) = 6.06

2
• Isoelectric pH values for the 20 protein-derived amino acids are
given in Table 3.2
Electrophoresis
• Electrophoresis: the process of separating
compounds on the basis of their electric charge
• electrophoresis of amino acids can be carried out
using paper, starch, agar, certain plastics, and
cellulose acetate as solid supports
• in paper electrophoresis, a paper strip saturated with
an aqueous buffer of predetermined pH serves as a
bridge between two electrode vessels
Peptide Bonds
• Individual amino acids
can be linked by forming
covalent bonds.
• Peptide bond: the
special name given to
the amide bond between
the -carboxyl group of
one amino acid and the
-amino group of
another amino acid
Geometry of Peptide Bond
• the four atoms of a peptide bond and the two alpha
carbons joined to it lie in a plane with bond angles of
120° about C and N
• to account for this geometry, a peptide bond is most
accurately represented as a hybrid of two contributing
structures (resonance structures)
• the hybrid has considerable C-N double bond
character and rotation about the peptide bond is
restricted
• See Figure 3.10
Peptides
• peptide: the name given to a short polymer of amino
acids joined by peptide bonds; they are classified by
the number of amino acids in the chain
• dipeptide: a molecule containing two amino acids
joined by a peptide bond
• tripeptide: a molecule containing three amino acids
joined by peptide bonds
• polypeptide: a macromolecule containing many
amino acids joined by peptide bonds
• protein: a biological macromolecule of molecular
weight 5000 g/mol or greater, consisting of one or
more polypeptide chains
Peptides with Physiological Activity
Peptides with Physiological Activity (cont’d)