Pharmaceutical
Organic Chemistry
By
Dr. Mehnaz Kamal
Assistant Professor,
Pharmaceutical Chemistry
Prince Sattam Bin Abdulaziz University
WELCOME
Amino acids
1-To know what is protein
2-To identify Types of protein
3- To Know amino acids
4- To differentiate between essential and
nonessential amino acids
5-To understand amino acids synthesis
Amino Acids
Characteristics and Structures
Amino acids are the building blocks of proteins. Each amino acid contains :
1.Amino group (-NH2 group)
2.Carboxyl group (-COOH group)
3.R group (side chain) which determines the type of an amino acid
All three groups are attached to a single carbon atom called chiral carbon. There are 20
common amino acids characterised by different R groups. (Different side chains make
different amino acids)
Amino Acids
Ball and stick model
The amino group is attached to the carbon
atom immediately next to the carboxylate
group that is α carbon, so, it is called α
amino acids
Other amino acids also exist called beta
and gamma amino acids, in which the
amino group is attached to the carbon
which is next to α carbon called α amino
acid
Amino Acids
α-Amino Acids
α -Amino Acids have the amino group α(on the next carbon) to the
carbonyl group.
R O
H2NCHCOH
a carbon
α -Amino acids are classified as neutral, acidic, basic, primary, and
secondary, depending on the R group.
Amino Acids
α-Amino acids are neutral, acidic, or basic.
O
CH3CHCOH
NH2
O
O
O
HOCCH2CHCOH
NH2
H2N(CH2)4CHCOH
NH2
neutral
acidic
basic
alanine
aspartic acid
lysine
Amino Acids
Most α-amino acids are primary, few are secondary.
O
CH3CHCOH
NH2
primary
secondary
alanine
proline
Amino Acids
Optical Activity
Only glycine is not
optically active
R H
C*
O
H 2N
C
OH
H H
C
O
H 2N
C
OH
glycine
all others are optically active (they are chiral)
• L-amino acids are naturally occurring
• absolute configuration is S
Amino Acids
Zwitterions
A Zwitterion is a dipolar ion. Since amino acids contain both an acid
and a base, an internal acid-base reaction forms a zwitterion.
R O
H2NCHCOH
amino acid
R O
H3NCHCO
zwitterion
Amino acids exist primarily as zwitterions.
Amino Acids
Amino acid zwitterions are amphoteric. They can react as either
acids or bases.
R O
H3NCHCO
zwitterion
R O
H3NCHCO
zwitterion
In acid solution
+
+ H 3O
R O
H3NCHCOH
protonated
In base solution
+ OH
-
+ H 2O
R O
H2NCHCO
deprotonated
+ H 2O
Amino Acids
Isoelectric Points
The isoelectric point of an amino acid occurs at the pH where the
amino acid exists as the zwitterion.
R O
H3NCHCOH
protonated
acid solution
low pH
+
H3O
R O
H3NCHCO
zwitterion
isoelectric
point
OH
-
R O
H2NCHCO
deprotonated
base solution
high pH
Amino Acids
There are 20 amino acids derived
from proteins.
While there are several methods of
categorizing them.
one of the most common is to group
them according to the nature of their
side chains.
1-Nonpolar Side Chains
2-Polar, Uncharged Side Chains
3- Polar Amino Acids with Negative Charge
4-Polar Amino Acids with Positive Charge
Amino Acids
1- Nonpolar Side Chains
Non Polar Amino Acids have equal number of amino and carboxyl groups and are neutral
There are eight amino acids with
nonpolar side chains
*Glycine, alanine, and proline
(have small, nonpolar side chains and
are all weakly hydrophobic).
* Phenylalanine, valine, leucine,
isoleucine, and methionine
(have larger side chains and are more
strongly hydrophobic).
Amino Acids
2- Polar, Uncharged Side Chains
These amino acids do not have any charge on the 'R' group. These amino acids participate in
hydrogen bonding of protein structure
There are also eight amino acids with polar, uncharged side chains.
Serine and threonine have hydroxyl groups. Asparagine and glutamine have amide groups.
Histidine and tryptophan have heterocyclic aromatic amine side chains.
Cysteine
has a sulfhydryl group. Tyrosine
has a phenolic side chain.
Tryptophan
Amino Acids
There are four amino acids with charged side chains.
3- Polar Amino Acids with Negative Charge
*Aspartic acid and glutamic
acid
have carboxyl groups than
amino groups on their side chains
making them acidic
4-Polar Amino Acids with Positive Charge
more amino groups as compared to carboxyl
groups making it basic
*Arginine and lysine have side
chains with amino groups.
Name
Abbreviation
Linear Structure
Alanine
ala A
CH3-CH(NH2)-COOH
Arginine
arg R
HN=C(NH2)-NH-(CH2)3-CH(NH2)-COOH
Asparagine
asn N
H2N-CO-CH2-CH(NH2)-COOH
Aspartic Acid
asp D
HOOC-CH2-CH(NH2)-COOH
Cysteine
cys C
HS-CH2-CH(NH2)-COOH
Glutamic Acid
glu E
HOOC-(CH2)2-CH(NH2)-COOH
Glutamine
gln Q
H2N-CO-(CH2)2-CH(NH2)-COOH
Glycine
gly G
NH2-CH2-COOH
Histidine
his H
NH-CH=N-CH=C-CH2-CH(NH2)-COOH
Isoleucine
ile I
CH3-CH2-CH(CH3)-CH(NH2)-COOH
Name
Abbreviation
Linear Structure
Leucine
leu L
(CH3)2-CH-CH2-CH(NH2)-COOH
Lysine
lys K
H2N-(CH2)4-CH(NH2)-COOH
Methionine
met M
CH3-S-(CH2)2-CH(NH2)-COOH
Phenylalanine
phe F
Ph-CH2-CH(NH2)-COOH
Proline
pro P
NH-(CH2)3-CH-COOH
Serine
ser S
HO-CH2-CH(NH2)-COOH
Threonine
thr T
CH3-CH(OH)-CH(NH2)-COOH
Tryptophan
trp W
Ph-NH-CH=C-CH2-CH(NH2)-COOH
Tyrosine
tyr Y
HO-Ph-CH2-CH(NH2)-COOH
Valine
val V
(CH3)2-CH-CH(NH2)-COOH
Amino Acids
Importance of Amino Acids
Amino acids are the building blocks of protein and you get
protein from your diet.
If you eat a variety of healthy protein-containing foods,
you will get all of the nine essential amino acids that your
body can't make for itself.
Amino acids combine into small chains via chemical
reactions called ‘condensation reactions’ in which the
carboxyl group and the amino group bond to one
another. These small chains that contain a few amino
acids linked together are called polypeptide chains
(the individual amino acids are called petides).
Polypetide chains, in turn, combine into the more
complex structures known as proteins
Amino Acids
Amino acids can be found in most of the nutrients we eat. Amino acids are the
building blocks of healthy protein. If the food consumed is rich in protein, our body
digests the protein right down to individual amino acids and little links of amino acids
is adequate to be taken over into the blood stream
Amino Acids
Essential amino acids
There are nine amino acids that cannot be synthesized in the body. Histidine, isoleucine,
leucine, lysine, methionine, phenylalanine, threonine, tryptophan and valine. We need these
amino acids in specific amounts daily in our diet.
PVT
TIM
HLL
Amino Acids
Non Essential amino acids
One of 11 amino acids that are synthesized in the body and are therefore not
necessary in the diet.
Seven of them considered conditionally essential in the human diet, meaning their
synthesis can be limited under special pathophysiological conditions, such as
prematurity in the infant or individuals in severe catabolic distress (These seven are
arginine, cysteine, glycine, glutamine, serine, proline and tyrosine)
Arginine is essential for infants but not for adults.
Four amino acids are dispensable in humans, meaning they can be synthesized in the
body. These four are alanine, aspartic acid, asparagine and glutamic acid.
Ornithine is 21st amino acid. Pyrrolysine, sometimes considered "the 22nd amino acid",
is not listed here as it is not used by humans
Amino Acids
The Eleven
"Nonessential" Amino Acids
The Nine "Essential"
Amino Acids
Alanine
Asparagine
Aspartate
Histidine
Isoleucine
Cysteine (requires sulfhydryl
group from methionine)
Leucine
Glutamate
Lysine
Glutamine
Methionine
Glycine
Phenylalanine
Proline
Threonine
Serine
Tyrosine (synthesized from
phenylalanine)
Arginine
Tryptophan
Valine
Amino Acids
As can be seen, the amino acids
possess both functional groups
required to form an amide.
Each amino acid is both a
carboxylic acid and an amine
simultaneously.
Therefore, it should
be possible to link
amino acids together
through
the
formation of amides.
The result is the formation of a
peptide or a protein, depending
upon how many amino acids
there are.
O
H2N
CH C
O
OH
H2N
CH C
R1
OH
H2N
R2
O
H2N
O
CH C
R1
R3
O
H
N
CH C
R2
CH C
O
H
N
CH C
R3
Peptide bond
(an amide linkage)
OH
OH
Amino Acids
Peptides and Proteins
• Peptides are named according to the number of amino acids
that are linked:
– dipeptide: two amino acids
– tripeptide: three amino acids
– tetrapeptide: four amino acids
– Polypeptide - < 50 amino acids
– Proteins-polymers of > 50 amino acids
peptide bond
O
O
H2N
CH C OH
R
a-amino acid
H 2N
CH C
R
peptide bond
peptide bond
O
O
HN CH C NH CH C
NH CH C
O
O
NH CH C OH
R
dipeptide
R
R
polypeptide
R
n
Amino Acids
Synthesis of amino acids
Strecker amino-acid synthesis
is a series of chemical reactions that synthesize an amino acid from an aldehyde or
ketone
The aldehyde is condensed with ammonium chloride in the presence of
potassium cyanide to form an α-aminonitrile, which is subsequently
hydrolyzed to give the desired amino-acid.
Amino Acids
Reaction mechanism
First part
*In the first part of the reaction, the carbonyl oxygen of an aldehyde is protonated,
*followed by a nucleophilic attack of ammonia to the carbonyl carbon.
*After subsequent proton exchange, water is cleaved from the iminium ion intermediate.
*A cyanide ion then attacks the iminium carbon yielding an aminonitrile.
Amino Acids
Reaction mechanism
second part
*the nitrile nitrogen of the
aminonitrile is protonated, and
the nitrile carbon is attacked by
a water molecule.
* 1,2-diamino-diol is then
formed after proton exchange
and a nucleophilic attack of
water to the former nitrile
carbon.
*Ammonia is subsequently
eliminated after the protonation
of the amino group, and finally
the deprotonation of a hydroxyl
group produces an amino acid.
Information Enrichment
Linkage with the life sciences
Protein Digestion: Part 1
Protein Digestion: Part 2
Figure 6.6
Protein Digestion: Part 3
Figure 6.6
Protein Digestion: Part 4
Figure 6.6
Possible symptoms of amino acid
deficiencies and imbalances
If amino acid supply is inadequate to meet your
body’s needs, a whole host of important functions can
begin to suffer.
This results in the appearance of signs and symptoms
ranging from immune system effects to
cardiovascular disease to emotional disorders and
more.
Typical symptoms I see when folk are deficient in
amino acids include:
•Low energy levels (even chronic fatigue)
•Depression
•Anxiety
•Memory and concentration problems
•Low thyroid function (which affects everything!)
•Allergic symptoms
•Digestive symptoms
•Inability to detoxify properly
•Loss of muscle mass
•Increased body fat