CHEM 160

AMINO ACIDS and PEPTIDES

CHEM 160

AMINO ACIDS and PEPTIDES

Objectives
Illustrate the general formula of amino acids
and describe the importance of each functional
group attached to the alpha carbon
Discuss the amphoteric property of amino acids
and predict their structure at any given pH
Recognize and classify amino acids based on
physical and chemical properties
Illustrate how amino acids are linked to form
the four levels of structure in proteins

AMINO ACIDS

General Structure
-carboxyl group

-carbon

2
-amino group

Side chain
confers the
identity of the
amino acid

General Structure

General Structure
At Neutral pH (pH = 7)
Predominantly dipolar or Zwitterions

General Structure
ZWITTERIONIC FORM
Explains the physical properties of amino acids
Crystalline solid
Very high melting
point
High solubility in
water

General Structure
Except for glycine, amino acids have an
asymmetric carbon
Four different groups of atoms
bonded to the -carbon
Chiral molecule

Optically active

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General Structure
STEREOCHEMISTRY
Amino acids can exist as a pair of Enantiomers

D- and L- are absolute configurations around the

chiral carbon

General Structure
STEREOCHEMISTRY
D and L configuration

General Structure
STEREOCHEMISTRY
Amino acid residues in naturally occuring
protein molecules are exclusively L-isomers
D-amino acids are found only in a few peptides
(eg. bacterial cell wall and some antibiotics)

Classifying Std. Amino Acids

Based on Nutritional Requirement
ESSENTIAL amino acids must be supplied in
the diet since they cannot be synthesized by
the human body
tryptophan
valine
threonine
isoleucine
leucine
lysine
phenylalanine methionine
histidine
arginine

NON-ESSENTIAL amino acids can be

synthesized by the body

Classifying Std. Amino Acids

Based on Structure (functional groups in the
side chain)
Alkyl/Aliphatic

Sulfur-containing
Alcohols

Aromatics
Acidic

Basic
Amides

Alkyl/Aliphatic
Stabilize proteins through hydrophobic
interaction

Glycine
(Gly, G)

Alanine
(Ala, A)

Proline
(Pro, P)

Proline limits structural flexibility because of its

rigid ring

Alkyl/Aliphatic
Stabilize proteins through hydrophobic
interaction

Leucine
(Leu, L)

Isoleucine
(Ile, I)

Valine
(Val, V)

Sulfur-Containing
Methionine is very
hydrophobic
Cysteine is
responsible for
disulfide bridges in
proteins

Cysteine
(Cys, C)

Methionine
(Met, M)

Alcohols
Stabilize protein
and interact with
the aqueous
environment
through hydrogen
bonding

Threonine
(Thr, T)
Serine
(Ser, S)

Aromatics

Phenylalanine
(Phe, F)
Tyrosine
Stabilize protein through (Tyr, Y)
hydrophobic interaction
Tyr (OH) can participate in H-bonding

Tryptophan
(Trp, W)

Aromatics
Trp and Tyr account for absorbance of light
exhibited by most proteins at 280 nm.

Aromatics
Absorbance at 280
nm is used for
spectrophotometric
determination of
protein
concentration

Acidic
Have COOH side
chains which are
ionized at pH 7

Negatively charged
Aspartic Acid/
Aspartate
(Asp, D)
Glutamic Acid/
Glutamate
(Glu, E)

Basic

Lysine
(Lys, K)

Histidine
(His, H)

Arginine
(Arg, R)
Have NH2 side chains which are protonated at
pH 7; positively charged

Amides
Amide counterparts
of acidic amino
acids

Asparagine
(Asn, N)

Can stabilize
protein by hydrogen
bonding
Glutamine
(Gln, Q)

You must
Be familiarized with the structures of the 20
standard amino acids

Remember their classifications

Memorize their names both the three-letter
e
and single letter names

Some Uncommon Amino Acids

4-hydroxyproline
can be found in
plant cell wall
proteins
e

Both are found

in collagen

Some Uncommon Amino Acids

-found in myosin
e

-found in prothrombin
(blood clotting protein

Some Uncommon Amino Acids

-found in elastin

Some Uncommon Amino Acids

-metabolites in the biosynthesis of arginine

and in the urea cycle

PROTONIC EQUILIBRIA
OF AMINO ACIDS

Amino Acids are Amphoteric

-OH

COOH

H2O
pKa1

H3N C H

H2O
pKa2

H3N C H

R
H2O

(+1)

COO-

-OH

H3O+

COOH2N C H

H2O

e
(0)

low pH

Isoelectric point or pH
(pI or IpH)

H3O+

(-1)
high pH

Isoelectric point or IpH

The pH wherein the net charge of the
molecule is ZERO

+
=

e
Which pKa values to consider?

Glycine

pKa - NH3+

pKa -COOH = 2.34

IpH

pKa -NH3+ = 9.60

IpH = 5.97

pKa COOH

Glutamic
Acid
pKa -COOH =
2.19
pKa side chain =
4.25

pKa -NH3+ =
9.67
IpH = 3.22

Lysine
pKa -COOH =
2.18
pKa -NH3 =
8.95
+

pKa side chain

= 10.53
IpH = 9.74

Paper Electrophoresis
Can be used to separate amino acids on the
basis of net electric charge

Spots can be visualized using ninhydrin

PEPTIDES

Formation of a Peptide Bond

Peptide bonds are formed by condensation
reaction of amino acids

Some terminologies
PEPTIDES/OLIGOPEPTIDES
continuous chains of a few amino acids
usually not more than 50 residues

POLYPEPTIDES

amino acid chains with MW < 10,000 Da

PROTEINS
amino acid chains with MW 10,000 Da

Peptides

Amino- or Nterminal residue

Carboxyl- or Cterminal residue

Drawing Peptides
Serine (N-terminal residue) glycine
phenylalanine alanine leucine (C-terminal
residue)

H3N

CH C

NH CH C

CH2OH

NH CH C

NH CH C

NH CH C

CH3

CH2
CH
H3C

CH3

Naming Peptides
Start with the N-terminal residue
Replace ine of names with yl for all residues
except that for the C-terminal residue
Write the whole name as one word
H3N

e O

CH C

NH CH C

NH CH C

NH CH C

NH CH C

CH2OH

CH2

CH3

CH2
CH
H3C

CH3

serylglycylphenylalanylalanylleucine

Sequence of Peptides
Three-letter or single-letter designations may
be used
Sequence: N-terminal to C-terminal residue
H3N

CH C

NH CH C

NH CHe C

NH CH C

NH CH C

CH2OH

CH2

CH3

CH2
CH
H3C

ser-gly-phe-ala-leu
SGFAL

CH3

Properties of Peptide Bond

0.123 nm
0.133 nm
e

0.145 nm

peptide bond (CN) length: 0.133nm

shorter than the adjacent CN bond (0.145nm)
longer than the C=O bond length of 0.123nm

Properties of Peptide Bond

Semi-rigid bond
Exhibits partial double bond character due to
resonance
e

O
O

C
R
'
C
R
'
R
N
R
N

H
H

Chemically stable inert and not easily cleaved

Acid-Base Properties of Peptides

All -NH2 and -COOH involved in peptide
(amide) bond formation are not anymore
basic/acidic.
Ionizable groups in a peptide include:
e
Amino group of the N-terminal residue
Carboxyl group of the C-terminal residue
side chains of the acidic and basic amino
acids

Example
Consider the peptide: Ser-Gly-Asp
1. Give the sequence using the single letter
designation
2. Draw the fully protonated form of the
e
tripeptide and examine
the protonic
equilibria
3. Predict the net charge at pH 8.0
4. Draw the structure of the tripeptide as it
would exist at pH 8.0

Example
Consider the peptide: Ser-Gly-Asp
a-COOH

a-NH3+

Side chain

Serine

2.21

9.15

---

Glycine

2.34

9.60

---

Aspartic acid

1.88

9.60

3.65

Biological Activities of some

Peptides
As HORMONES (chemical
messengers of the body)
INSULIN
responsible for the
absorption of
glucose from the
blood stream

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Biological Activities of some

Peptides
As HORMONES (chemical
messengers of the body)
OXYTOCIN a
nonapeptide that
stimulates uterine
contraction

Biological Activities of some

Peptides
As HORMONES (chemical
messengers of the body)
VASOREPRESSIN a
nonapeptide that
prevents urination
at night

Synthetic Peptides
ASPARTAME a dipeptide aspartylphenylalanyl
methyl ester used as artificial sweetener
e

References
CHEM 160 lecture slide of Profs. BP Serrano, KMP Caldo and AC Reyes
Nelson and Cox. Lehningers Principles of Biochemistry, 4th ed.