Download Amino Acids and Peptides

Amino Acids
& Peptides
1
Chapter Outline

Amino Acids 5.1
– Amino acid classes (G1)
– Stereoisomers (G2)
– Bioactive AA
– Titration of AA (G3)
– Modified AA
– AA reactions

Peptides 5.2
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General Properties
There are 20 standard amino acids. With
exception of proline, all have primary
amino group and a carboxylic acid bonded
to same carbon.
 Carboxyl group and amino group all have
pKa values around 2.2 and 9.4
respectively

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Note that at physiological pH of 7, amino acids
are charged as shown to right. They can act as
either acid or base.
 Also referred to as zwitterions
 This imparts special properties e.g. some have
melting points of 300 C, just like salts. Also very
soluble in water and not organics.
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
AMINO ACIDS
Overview

The general structure of an amino acid
molecule, with the amine group on the
right and the carboxylic acid group on the
left. The R group is dependent on the
amino acid.
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AAs overview cont..

In chemistry, an amino acid is any
molecule that contains both amine and
carboxylic acid functional groups. In
biochemistry, this shorter and more
general term is frequently used to refer to
alpha amino acids: those amino acids in
which the amino and carboxylate
functionalities are attached to the same
carbon, the so-called α–carbon.
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AAs overview cont..

An amino acid residue is what is left of
an amino acid once a molecule of water
has been lost (an H+ from the
nitrogenous side and an OH- from the
carboxylic side) in the formation of a
peptide bond.
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AAs overview cont..
Amino acids are the basic structural building
units of proteins. They form short polymer
chains called peptides or polypeptides which
in turn form structures called proteins. The
process of such formation from an mRNA
template is known as translation, which is
part of protein synthesis.
 Phenylalanine is one of the standard
amino acids.

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AAs overview cont..

Twenty amino acids are encoded by the
standard genetic code and are called
proteinogenic or standard amino acids.
Combinations of these amino acids
produce every single essential protein for
the homeostasis of the human body. At
least two others are also coded by DNA in
a non-standard manner
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AAs overview cont..
19 standard AAs have the same general
str.
 These molecules contain a central C atom
(the α-C) to amino group, carboxylate
group, H atom and R group are attached.

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AAs overview cont..

Proline is the only proteinogenic amino
acid whose side group cyclizes onto the
backbone: it links to the α-amino group,
and thus is also the only proteinogenic
amino acid containing a secondary amine
at this position.
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Amino Acid: Definition
An alpha amino acid is a carboxylic acid with an
amino group on the carbon alpha to the
carboxylic acid .
 The alpha carbon also has an R group side chain
except for glycine which has two Hs.

O
Generic amino
acid at physiological
pH: zwitterion form
C
O
+
H3N C H
R
aC
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Definition, cont.
 If
the R group is not H, the AA can
exist in two enantiomeric forms
(nonsuperimposable mirror image)
forms.)
O
O
O
O
C
C
+
H3N
a carbon
C
R1
H
H
Mirror plane
C
+
NH3
R1
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Amino Acids
General
form: 1. an amino
acid (AA); 2. two AA linked to
form the peptide bond.
O
C
+
H3N
L-form
C
R1
HO H HO
+
H3N C C N C C O
R1
R1
H
O
PEPTIDE BOND
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Amino Acids-2
 Only
the L form of amino acids is
commonly found in proteins.
 Depending on the nature of the R
group, AA are classified into four
groups.
nonpolar
polar
acidic
basic
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Hydrophobic Amino Acids 1
H3N
+
COO
C
H
CH3
alanine, Ala
H3N
+
H3N
+
COO
C
CH2
phenylalanine, Phe
COO
C
H
CH2
CH
CH3 CH3
leucine,Leu
H
H3N
+
COO
C
H
CH3 CH
CH2
CH3
isoleucine, Ile
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Hydrophobic Amino Acids 1
17
AA with nonpolar side chains-2
H 3N
+
COO
C H
CH
CH3 CH3
valine, Val
COO
H 2N
+
CH2
C H
CH2
CH2
proline, Pro
H 3N
+
COO
C
H
CH2CH2S CH3
methionine, Met
COO
H 3N
+
C H
CH2
C
CH
N
H
tryptophan, Trp
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Hydrophobic Amino Acids 2
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Neutral Nonpolar AA
Contain mostly HC R groups
 Neutral = R groups ≠ ± charges
 They interact poorly with water, nonpolar
(hydrophobic)
 Important role maintaining the 3-D protein
str

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AA with polar side chains-1
H3N
+
COO
C
H
H
Glycine, Gly
H3N
+
H3N
+
COO
C
CH2 OH
Serine, Ser
COO
C
H
CH2 SH
cysteine, Cys
H
H3N
+
COO
C H
CH OH
CH3
threonine, Thr
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Polar Amino Acids 1
22
AA with polar side chains-2
H3N
+
COO
C H
CH2
O C NH2
asparagine, Asn
H3N
+
COO
C
H
CH2
H3N
+
COO
C H
CH2
CH2
O C NH2
glutamine, Gln
tyrosine, Tyr
OH
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Polar Amino Acids 2
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Polar AA
Have functional groups capable of H
bonding; easily interact with water
 Give significant effect on protein stability

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AA: acidic and basic
H3N
+
COO
H3N
C H
CH2
O C O
aspartic acid, Asp
H3N
+
CH2
CH2
NH
+
H2N C NH2
arginine, Arg
C H
CH2 glutamic acid,
CH2 Glu
O C O
COO
C H
CH2
+
COO
H3N
+
COO
C H
CH2
CH2
CH2
CH2
+
NH3
lysine, Lys
H3N
+
H
C
+
HN
COO
C H
CH2
C
NH
C
H
histidine, His
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Charged Amino Acids
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
The side chains of aspartic acid and
glutamic acid are negatively charged
above pH 3.

The side chains of basic amino acids are
positively charged at physiological pH
values:
Lysine – has butylammonium side chain
Arginine – bears a guanidino group
Histidine – carries a imidazolium moeity
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Can form ionic bonds with acidic AA
 Play an important role in the catalytic
activity of numerous enzymes

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Bioactive AAs




In addition to protein synthesis, amino acids
have other biologically-important roles.
Glycine and glutamate are
neurotransmitters as well as standard amino
acids in proteins. Many amino acids are
used to synthesize other molecules, for
example:
Tryptophan is a precursor of the
neurotransmitter serotonin.
Glycine is one of the reactants in the
synthesis of porphyrins such as heme.
Arginine is used to synthesize the hormone
nitric oxide.
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Bioactive AAs cont….

Numerous non-standard amino acids are
also biologically-important: Gammaaminobutyric acid is another
neurotransmitter, carnitine is used in lipid
transport within a cell, ornithine, citrulline,
homocysteine, hydroxyproline,
hydroxylysine, and sarcosine.
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Bioactive AAs cont….
The 20 standard amino acids undergo a
bewildering number of chemical
transformations to other amino acids and
related compounds as part of their normal
cellular synthesis and degradation.
 Many organisms use certain amino acids
to transport nitrogen in the form of amino
groups.
 Amino acids may also be oxidized as
metabolic fuels to provide energy.

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Bioactive AAs cont….
Amino acids often function as chemical
messengers for communication between
cells.
 Alpha-aminobutric acid and dopamine are
neuro transmitters.
 Histamine is a mediator of allergic
reactions.

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Bioactive AAs cont….

Thyroxine stimulates vertebrate
metabolism.
 Many peptides (e.g. glutathione) have
physiological functions as hormones or
regulatory molecules.
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Modified AAs in Proteins
The ‘universal’ genetic code specifies only
the 20 essential amino acids.
 Other amino acids are components of
certain proteins resulting from the specific
modification of an amino acid residue after
the polypeptide chain has been
synthesized.

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Modified AAs in Proteins cont…
These modifications include the simple
addition of small chemical groups to
certain amino acid chains: hydroxylation,
methylation, acetylation, and
phosphorylation.
 Larger groups, including lipids and
carbohydrate polymers, are attached to
particular amino acid residues of certain
proteins
 Examples: γγ-carboxyglutamate, 4hydroxyproline

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AA Stereoisomer
Most amino acids occur in two possible
optical isomers, called D and L. The L
amino acids represent the vast majority of
amino acids found in proteins.
 D amino acids are found in some proteins
produced by exotic sea-dwelling
organisms, such as cone snails. They are
also abundant components of the
proteoglycan cell walls of bacteria.

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
The D-isomer of aspartic acid is found in
some proteins as the result of a
spontaneous post-translational
modification associated with protein aging
or as the by-product of enzymatic
modification catalyzed by protein Lisoaspartyl methyltransferase.
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All amino acids (except glycine) recovered
from polypeptides are optically active and
direction of angle of rotation is measured
by polarimeter.
 Optically active molecules are asymmetric
and the central atoms (C-alpha atoms of
amino acids) in such molecules are chiral
centers with property of chirality.

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These asymmetric centers give rise to
enantiomers (nonsuperimposable mirror
images of one another) or are
stereoisomers (chiral molecules with
different configurations about at least one
of their asymmetric centers but which are
otherwise identical).
 Life is based on chiral molecules as
biosynthetic processes almost invariably
produce pure stereoisomers.

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Acid-Base Properties of AAs
Titration curve for glycine
 Note that one starts with all groups
in acid form.
 Note how many equivalents are
added
 Note that at 0.5 and 1.5
equivalents, pH is equal to pK of
group being titrated.
 Note pH which gives zero charge is
the isoelectric point. Calculated as
(pK1+pK2)/2
 Note where the buffering capacity is
best

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Amino Acid Titration
 At
physiological pH, the carboxyl
group of the AA is negatively charged
and the amino group is positively
charged.
 Amino acids without charged side
chains are zwitterions and have no
net charge. H3+N-CHR-COO-.
 A titration curve shows how the
amine and carboxyl groups react with
hydrogen ion.
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Amino Acid Titration
 At
low pH a nonacidic/nonbasic
amino acid is protonated and has
the structure below.
 H3N+CHRCOOH
 The charge behavior of acidic and
basic AAs is more complex.
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Titration of Alanine
B=C
pK2=9.73
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C
O
H3N CHC OH
R1 A
O
+
H3N CH C O
R1 B
O
+
H3N CH1C O
R1 C
+
pH
5
1
B, pI=pH=6.0
A
A=B
pK1=2.3
1
mole base added
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2
Isoelectric point
The isoelectric point (pI) for an AA occurs
when there is no net charge.
 For a neutral AA, the pI is calculated using
the equation pK1 + pK2/2
 Eg.: alanine: 2.34 + 9.7 / 2 = 6.0
 For acidic or basic AAs, the pI is the
average of the two pKa values bracketing
the isoelectric structure.

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More Titration Curves
AA with ionizable side
chains hv complex
titration curve
 Eg. Glutamic acid has a
carboxyl side chain
group
 At low pH it has net
charge +1. As base is
added, the α-carboxyl
group loses a proton to
become carboxylate
group.
 Glutamate now has no
net charge. As more
base is added

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More Titration Curves cont…




As more base is added,
the second carboxyl
group loses a proton and
the molecule has a -1
charge.
Adding additional base
results in the NH3 ion
lossing its proton.
At this point glutamate
has a net charge of -2.
the pI value for
glutamate is the halfway
btw the pKa values for
the 2 carboxyl group
pI = 3.22
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Peptide Bonds
Peptide bond formed from elimination of
water from 2 amino acids resulting in CONH linkage.
 Can have di-, tri-, oligo- and polypeptides.
 Proteins composed of linear polymer of
amino acids.

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
Large number of
proteins can exist. A
small protein of 100
amino acids can have
20100 or 1.27x10130
possible unique
polypeptide chains.
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Peptides

Peptide: a polymer of about 2-100 AAs linked by the
peptide(amide) bond. As the amino group and the
carboxyl group link, water is lost.
H O
H O
H O
+
+
+
H3N C C O H3N C C O H3N C C O
R1
-H2O
R1
-H2O
R1
H O
H O
H O
+
H3N C C N C C N C C O
H
H
R1
R1
R1
Peptide bonds
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Peptides




A peptide is written with the N-terminal end
to the left and the C-terminal end to the
right.
H2N-Tyr-Ala-Cys-Gly-COOH
Name = Tyrosylalanylcysteinylglycine
The peptide bond is rigid and planar due to
the resonance contribution shown below.
C
a
O
H
C N
Ca
C
a
+ H
C N
Ca
- O
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Peptides

The peptide bond
angles force specific
conformations of
proteins and, on
extended chains,
successive R groups
are on opposite
sides.
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Physiologically Interesting Peptides
 carbon
O
+
H3N CH2CH2C NH CH COO
-
-alanyl-L-histidine CH2
C
HC
NH
N C
Common name: carnosine
found in muscle tissue
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Physiologically Interesting Peptides
-
COO
+
O
O
-
H3N CH CH2 CH2 C NH CH C NH CH2COO
CH2
SH
-glutamyl-L-cysteineylglycine
Glutathione: the reduced form
reduces oxidizing agents by dimerizing to
form the disulfide bond with release of 2 H.
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Physiologically Interesting Peptides
Tyr-Gly-Gly-Phe-Leu
N-terminal AA
C-terminal AA
Short form description for a peptide.
Leucine enkephalin: a natural
analgesic found in the brain
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Physiologically Interesting Peptides
H3
3
+
N -Cys-Tyr-Ile
Oxytocin
Induces labor and
aids in forcing milk
from the mammary
glands.
|
|
S
Gln
|
|
S -Cys-Asn
|
8
Pro-Leu-Gly-NH2
Vassopressin has a Phe at position 3
instead of Ile and an Arg at position 8
instead of a Leu. Its role is in regulatin
blood pressure.
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THE END
Amino Acids
& Peptides
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