Proteins
• Proteins are long polymers made up of 20
different amino acid monomers
• They are quite large, with molar masses of around
5,000 g/mol to around 100,000 g/mol
• They have complex structures with unique 3-D
shapes that determine their functions
• They are the most abundant organic compounds in
the body, and also the most diverse in function
• Proteins are involved in structure, transport,
storage, metabolism, cell signaling and many other
processes
Functions of Proteins
Amino Acids
• Amino acids, as the name implies, have both an amine
group and a carboxylic acid group
• The 20 amino acids that make up our proteins have the
amine group, the acid group, a hydrogen, and a variable
group attached to a central carbon (called the  carbon)
• The variable groups (called side chains) are what
determine the individual characteristics of the amino acids
General structure of an amino acid:
R
R
H
H 2N
C
HO
H 2N
COOH
O
H
Acidic and Basic Amino Acids
• Amino acids can be classified by the nature of the sidechain as acidic, basic, polar neutral or nonpolar
Polar Neutral Amino Acids
Nonpolar Amino Acids
Abbreviations for Amino Acids
• Each amino acid has standard 3-letter and 1-letter
abbreviations (shown in the table below)
Name
Glycine
Alanine
Valine
3-Let
Gly
Ala
Val
1-Let
G
A
V
Name
Serine
Threonine
Asparagine
3-Let
Ser
Thr
Asn
1-Let
S
T
N
Leucine
Isoleucine
Phenylalanine
Leu
Ile
Phe
L
I
F
Glutamine
Tyrosine
Aspartic Acid
Gln
Tyr
Asp
Q
Y
D
Methionine
Proline
Met
Pro
M
P
Glutamic Acid
Lysine
Glu
Lys
E
K
Tryptophan
Cysteine
Trp
Cys
W
C
Arginine
Histidine
Arg
His
R
H
D- and L-Amino Acids
• All amino acids besides glycine are chiral
• Each amino acid has two possible enantiomers
- these are classified as D or L as with sugars
• Amino acids in nature are almost exclusively L-amino acids
• When a Fischer projection is written with the acid at the top,
and the R group at the bottom:
- if the amine group is on the right, it’s a D-amino acid
- if the amine group is on the left, it’s an L-amino acid
COOH
COOH
H
NH2
CH3
D-Alanine
H 2N
H
CH3
L-Alanine
Isoelectric Points for Amino Acids
• Because the amine group is basic, and the carboxylic acid group
is acidic, amino acids often exist as zwitterions
• A zwitterion is a dipolar ion with a net charge of zero
• Because zwitterions act like salts, they have high melting points
• The isoelectric point (pI) is the pH at which a zwitterion forms
- below pI the amino acid has a net positive charge
- above pI the amino acid has a net negative charge
• Acidic amino acids have low pI values and basic amino acids
have high pI values (due to side-chain ionization)
Electrophoresis of Amino Acids
• Electrophoresis is a technique used to separate charged
molecules with an electric field
• The samples are loaded onto a support medium (usually an
agarose or polyacrylamide gel) and separated by mobility
- mobility is affected by size, shape, charge and solubility
• A buffered solution is used to conduct the charge and allow the
charged molecules to move
- negatively charged amino acids move towards the anode (-)
- positively charged amino acids move towards the cathode (+)
Peptides
• Peptides are two or more amino acids linked together by amide
bonds (called peptide bonds)
• A peptide bond is formed when the acid group of one amino
acid reacts with the amine group of another amino acid
• When writing the structure of a peptide:
- the amino acid with the free (unreacted) amine group is
written on the left and is called the N terminal amino acid
- the amino acid with the free (unreacted) acid group is written
on the right and is called the C terminal amino acid
• Peptides are usually named using the 3- or 1-letter abbreviations
for the amino acids, going from N terminal to C terminal
Synthesis of Peptides and Proteins
• In cells, peptides and proteins are synthesized using RNA
catalysts (to be discussed in Chapter 22)
• In the laboratory a variety of techniques are used
- most commonly the peptides are synthesized on resin beads
using an automated peptide synthesizer
- smaller peptides, like dipeptides, are generally synthesized by
hand in solution (not on resin)
- protecting groups must be used in order to prevent unwanted
amino acid couplings
CH3
OH
H 2N
Protect
amine
P
P
N
H
N
H
O
O
O
OH
Deprotect
Protect
acid
O
H 2N
O
O
H
N
P
OH
O
H 2N
CH3
CH3
P
CH3
O
H
N
O
H 2N
OH
O
Structure of Peptide Bonds
• Peptides are particularly stable and are also fairly rigid
• This is due to the structure of the peptide amide bonds
• Through resonance, the lone pair electrons on nitrogen and
the pi electrons of the carbonyl are delocalized
- this gives some double bond character to the C-N bond,
preventing free rotation around that bond
- this also makes the nitrogen less basic, since the lone pair is
not very available for bonding, increasing peptide stability
O
O
NH2
Resonance Structures
O
NH2
NH2
Resonance Hybrid
Primary Structure of Peptides and Proteins
• A polypeptide containing 50 or more amino acids is usually
called a protein
• The primary structure of a protein is the sequence of amino
acids in the peptide chain
• The higher levels of structure, as well as the function, are
derived from the primary structure
- even a single amino acid change can have drastic effects
• For example, the nonapeptides oxytocin and vasopressin only
differ in the amino acids at positions 3 and 8
Insulin
• Insulin was the first protein whose primary
structure was determined
• Human, pig and cow insulin differ only at four
amino acids
• Bovine insulin (from cow pancreas) was used
for diabetics, but now it’s made by genetically
engineered E. coli
Secondary Structure of Proteins (the Alpha Helix)
• The secondary structure of a protein indicates the
conformation of the peptide chain in a given region
• There are three main types of secondary structure: the alpha
helix, the beta-pleated sheet and the triple helix
- all three are governed by hydrogen bonding
• The alpha helix is
coiled due to H-bonding
between backbone N-H
on one loop to backbone
C=O group on next loop
• The side chains are all
on the outside of the
helix, so larger side chain
groups favor  helix
Secondary Structure of Proteins (the Beta-Pleated Sheet)
• Beta-pleated sheets consist of peptide chains side-by-side,
held together by backbone H-bonding
• All the side chains point out above and below the sheet
- smaller side chains favor -pleated sheets (larger ones
would be too crowded)
Secondary Structure of Proteins (the Triple Helix)
• A triple helix consists of three peptide strands in a braid, held
together by H-bonding, both backbone H-bonding and Hbonding between hydroxyl groups on adjacent peptide strands
- they contain large amounts glycine, proline, hydroxyproline
and hydroxylysine that contain –OH groups for H-bonding
• Triple helices are very strong, and are found in collagen,
connective tissue, skin, tendons, and cartilage
- several triple helices can form a larger braid for increased
strength