Amino Acids

1/29/2003
 Amino Acids:
The building blocks of proteins

pK2 pK1

 amino acids because of the  carboxylic and  amino groups

pK1 and pK2 respectively pKR is for R group pK’s

pK1  2.2 while pK2  9.4

In the physiological pH range, both carboxylic and

amino groups are completely ionized
 Amino acids are Ampholytes
They can act as either an acid or a base

They are Zwitterions or molecules that have both

a positive and a negative charge

Because of their ionic nature they have

extremely high melting temperatures
 Amino acids can form peptide
bonds
Amino acid residue Proteins are
peptide units molecules that
dipeptides
consist of one or
more
tripeptides polypeptide
oligopeptides chains
polypeptides

Peptides are linear polymers that range from 8 to 4000

amino acid residues
There are twenty (20) different naturally occurring
amino acids
 Linear arrays of amino acids can
make a huge number of molecules
Consider a peptide with two amino acids
AA1 AA2
20 x 20 = 400 different molecules

AA1 AA2 AA3

20 x 20 x 20 = 8000 different molecules

For 100 amino acid protein the # of possibilities are:

20100  1.27 x10130

The total number of atoms in the universe is estimated at 9x1078
 Characteristics of
Characteristics of Amino
Amino Acids
Acids
There are three main physical categories to describe amino
acids:

1) Non polar “hydrophobic” nine in all

Glycine, Alanine, Valine, Leucine, Isoleucine,
Methionine, Proline, Phenylalanine and Tryptophan

2) Uncharged polar, six in all

Serine, Threonine, Asparagine, Glutamine Tyrosine,
Cysteine

3) Charged polar, five in all

Lysine, Arginine, Glutamic acid, Aspartic acid, and
Histidine
 Amino Acids
You must know:

Their names
Their structure
Their three letter code
Their one letter code
O

H2N CH C OH

CH2

Tyrosine, Tyr, Y, aromatic, hydroxyl

OH
Cystine consists of two disulfide-linked
cysteine residues
 Acid - Base properties of amino acids
 [A - ] 
pH  pK  log 
 [HA] 
Isoelectric point: the pH where
a protein carries no net
electrical charge

pI  pK i  pK j 
1
2
For a mono amino-mono carboxylic
residue pKi = pK1 and pKj = pK2 ; for
D and E, pKi = pK1 and pKj - pKR ;
For R, H and K, pKi = KR and pKj =
 The tetra peptide Ala-Tyr-Asp-Gly or AYDG

Greek lettering used to identify atoms in lysine or glutamate

 Optical activity - The ability to rotate plane - polarized
light

Asymmetric carbon atom

Chirality - Not superimposable

Mirror image - enantiomers

Operational
(+) Dextrorotatory - right - clockwise definition only

(-) Levorotatory - left counterclockwise

} cannot predict
absolute
configurations
Na D Line passed through polarizing filters.
 Stereoisomers
Stereoisomers
One or many chiral centers

N chiral centers 2N possible stereoisomers and 2N-1 are

enantiomeric
For N = 2
there are 4 possible sterioisomers
of which 2 are enatiomers
and 2 are diastereomers

Diastereomers are not mirror images and have

different chemical properties.
 The Fischer Convention
Absolute configuration about an asymmetric carbon

related to glyceraldehyde
(+) = D-Glyceraldehyde
(-) = L-Glyceraldehyde
All naturally occurring amino acids that make up
proteins are in the L conformation

In the Fischer projection all bonds in the horizontal

direction is coming out of the plane if the paper, while
the vertical bonds project behind the plane of the paper

The CORN method for L

isomers: put the hydrogen
towards you and read off
CO R N clockwise
around the C This works
for all amino acids.
An example
An example of
of an
an amino
amino acid
acid with
with two
two
asymmetric carbons
asymmetric carbons
 Cahn - Ingold - Prelog system
Can give absolute configuration nomenclature to multiple
chiral centers.

Priority

Atoms of higher atomic number bonded to a chiral center

are ranked above those of lower atomic number with
lowest priority away from you R highest to lowest =
clockwise, S highest to lowest = counterclockwise

SH>OH>NH2>COOH>CHO>CH2OH>C6H5>CH3>H
The major advantage of the CIP or RS system is
that the chiralities of compounds with multiple
asymmetric centers can be unambiguously
described
 Prochiral substituents are
distinguishable
Two chemically identical substituents to an
otherwise chiral tetrahedral center are geometrically
distinct.
 Planar objects with no rotational symmetry also
have prochariality
Flat trigonal molecules such as aldehydes can be prochiral
With the flat side facing the viewer if the priority is
clockwise it is called the (a) re face (rectus) else it is the
(b) si face (sinistrus).
 Lecture 6 Monday Feb 3
• Protein Geometry
• Primary sequence
• Sequence alignments