Download Amino Acids and Peptides

Amino Acids and Peptides
Dr. Henry O. Ogedegbe
Department of EHMCS
Amino Acids-Formula and Three
Dimensional Structure
• Proteins are polypeptides of amino acids linked together by
peptide bonds
• The positively charged nitrogen containing amino group is
on one side and negatively charged carboxyl group is at the
other end
• Along the chain is a series of different side chains that are
different for each of the amino acids
• A linkage of two amino acids is a dipeptide while the
linkage of three amino acids is a tripeptide
• For a chain 20 amino acids long there are more than a
billion possible sequences
Amino Acids-Formula and Three
Dimensional Structure
• Only 20 amino acids are found in proteins
• The general structure involve an amino group and a
carboxyl group both bonded to the -carbon
• The -carbon is also bonded to a hydrogen and a side
chain group represented by the letter R
• The R group gives identity to the particular amino acid
• An important property of the amino acids are their
stereochemistry or three dimensional shape
• The -carbons in all amino acids except glycine have four
different groups bonded to them
Amino Acids-Formula and Three
Dimensional Structure
• This gives rise to two nonsuperimposable mirror image
forms or chiral forms
• Glycine has two hydrogen atoms bonded to the -carbon
• These nonsuperimposable mirror image forms are referred
to as stereoisomers
• The two stereoisomers of amino acids are classified into L
or D forms from the latin laevus and dexter
• Glyceraldehyde is the standard molecule from which other
chiral compounds are compared
• In the L form of glyceraldehyde the hydroxyl group is on
the left side of the molecule
Amino Acids-Formula and Three
Dimensional Structure
• In the D form the hydroxyl group is on the right side of the
molecule
• In an amino acid, the position of the amino group on the
left or right side of the -carbon determines the L or D
designation
• The amino acids in proteins are the L forms
• Most D amino acids in nature occur in bacterial cell walls
and in some antibiotics but they are not found in protein
Amino Acids-Formula and Three
Dimensional Structure
Amino Acids-Formula and Three
Dimensional Structure
The Structure and Properties of the
Individual Amino Acids
• The classification of the amino acids are based on several
criteria including
–
–
–
–
Polar or non polar
Presence of an acidic or basic group in the side chain
Presence of functional groups in the side chains
Nature of those groups
• In the case of glycine two hydrogen atoms are bonded to
the -carbon
• In all other amino acids the the side chain is larger and
more complex
The Structure and Properties of the
Individual Amino Acids
• Side chain carbon atoms are designated with Greek
alphabets counting from the -carbon
• The carbon atoms are in turn , , , and  and the terminal
carbon atom is referred to as -carbon
• Amino acids may be referred to by the three or one letter
abbreviation of their names
• Group 1 Amino Acids with Nonpolar Side Chains:
• This group consist of alanine, valine, leucine, isoleucine,
proline, phenylalanine, tryptophan, and methionine
• Glycine may be added to this group because it lacks a polar
side chain
The Structure and Properties of the
Individual Amino Acids
• Members of the group including alanine, valine, leucine,
and isoleucine have aliphatic hydrcarbon side chains
• Proline has an aliphatic cyclic structure and the nitrogen is
bonded to two carbon atoms
• The amino acid of proline is a secondary amine unlike all
other common amino acids which are primary amines
• The hydrocarbon group in phenylalanine is aromatic
• The side chain in tryptophan contains an indole-ring which
is aromatic
The Structure and Properties of the
Individual Amino Acids
• Group 2 Amino Acids with Electrically Neutral Polar Side
Chains:
• This group of amino acids have polar side chains that are
electrically neutral at neutral pH
• The group includes serine, threonine, tyrosine, cysteine,
glutamine, and asparagine.
• Glycine may also be included in this group because it lacks
a nonpolar side chain
• In threonine and serine, the polar group is a hydroxyl (OH)
bonded to an the aliphatic hydrocarbon groups
The Structure and Properties of the
Individual Amino Acids
• In tyrosine, the hydroxyl group in bonded to an aromatic
hydrocarbon group which is a phenol
• It is a stronger acid than an aliphatic alcohol
• Side chain of tyrosine can lose a proton whereas those of
serine and threonine do not
• The polar side chain in cysteine consist of an –SH (thio)
group
• They reacts with other cysteine molecule to form disulfide
(– S – S –) bridges in proteins and in an oxidative reaction
• The thio group can lose a proton
The Structure and Properties of the
Individual Amino Acids
• Asparagine and glutamine have amide groups which are
derived from carboxyl groups in the side chains
• Asparagine and glutamine may be considered as
derivatives of the group 3 amino acids glutamic acid and
aspartic acid
• Group 3 Amino Acids with Carboxyl Groups in Their Side
Chains:
• Aspartic acid and glutamic acids have carboxyl groups in
their side chains in addition to the one present in all amino
acids
• A carboxyl group can lose a proton and form the
corresponding carboxylate anion glutamate and aspartate
The Structure and Properties of the
Individual Amino Acids
• As a result of presence of the carboxylate, the side chains
are negatively charged at neutral pH
• The side chain carbonyls form side chain amide groups
with – NH2 to yield glutamine and asparagine
• The side chains amide groups are electrically neutral at
neutral pH like the other group 2 amino acids
• Group 4 Amino Acids with Basic Side Chains:
• Histidine, lysine and arginine have basic side chains
• In lysine and arginine side chains are positively charged at
neutral pH
The Structure and Properties of the
Individual Amino Acids
• The pKa of histidine side chain, imidazole group is 6.0
which is close to physiological pH
• Properties of many proteins depend on whether or not
individual histidine residues are charged
• Histidine facilitates enzyme reactions by serving as a
proton donor/acceptor
• The side chain amino group in lysine is attached to an
aliphatic hydrocarbon tail
• In arginine the side chain basic group the guanidino group
is complex in structure and bonded to an aliphatic
hydrocarbon tail
The Structure and Properties of the
Individual Amino Acids
The Structure and Properties of the
Individual Amino Acids
The Structure and Properties of the
Individual Amino Acids
The Structure and Properties of the
Individual Amino Acids
• Uncommon Amino Acids:
• The uncommon amino acids are derived from common
amino acids
• They are produced by modification of parent amino acid
after protein synthesis by the organism
• This is a process known as post translational modification
• Hydroxyproline and hydroxylysine are examples
• They differ from the parent in having hydroxyl groups on
their side chains
• They are found in few connective tissue proteins such as
collagen
The Structure and Properties of the
Individual Amino Acids
• Thyroxine is different from tyrosine in having an extra
iodine containing aromatic group on the side chain
• It is found only in the thyroid gland
Titration Curve of The Amino Acids
• Carboxyl group and amino group of free amino acids are
charged at neutral pH
• The carboxylate portion is negatively charged and the
amino group positively charged
• Amino acids without charged groups on their side chains
exist in neutral solutions as zwitterions with no net charge
• A zwitterion has equal positive and negative charges in
solution
• It is electrically neutral
• Titration curve of an amino acid indicates the reaction of
each functional group with hydrogen ions
Titration Curve of The Amino Acids
Titration Curve of The Amino Acids
• In alanine, the carboxyl and amino groups are the two
titratable groups
• At very low pH alanine has a protonated carboxyl group
and a positively charged protonated amino group
• Thus alanine has under such conditions a net positive
charge of 1
• When base is added, the carboxyl group loses its proton
and it becomes negatively charged carboxylate group
• At this point, alanine now has no net charge
• As more base is added, the protonated amino group loses
its proton and alanine now has a negative charge of 1
Titration Curve of The Amino Acids
Titration Curve of The Amino Acids
• The titration curve of alanine is that of a diprotic acid
Titration Curve of The Amino Acids
• In histidine, the imidazole side chain contributes a
titratable group
• At low pH the the histidine has a net positive charge of 2
– Both amino group and imidazole have positive charges
• As base is added the the carboxyl group loses a proton and
becomes a carboxylate
• The histidine now has a positive charge of 1
• As more base is added, the charged imidazole loses its
proton and the histidine has no net charge
• At higher pH the amino group loses its proton and the
histidine now has a net negative charge of -1
• The titration curve of histidine is that of a triprotic acid
Titration Curve of The Amino Acids
Titration Curve of The Amino Acids
Titration Curve of The Amino Acids
• The amino acids have characteristic Kas and pKas of their
titratable groups
• The pKas of -carboxyl groups are low at around 2 while
the pKas of amino acid groups range from 9 to 10.5
• The pKas of side chains depend on the groups chemical
nature
• Classification of an amino acid as an acid or a base
depends of the pKa of the side chain
• The side groups are still titratable after incorporation of the
amino acid in a protein
• The pKa of the titratable group on the side chain may not
be the same as in a free amino acid
Titration Curve of The Amino Acids
• Amino acids, peptides and proteins can have different
charges at a given pH
• Alanine and histidine both have net charges of -1 at high
pH above 10
– The carboxylate is the charged anion
• At lower pH around 5 alanine is a zwitterion with no net
charge but histidine has a net charge of +1 at pH 5
• The imidazole group is protonated.
• This is the basis of electrophoresis a method for separating
molecules based on their charges
• The pH at which a molecule has no net charge is called the
isoelectric point
Titration Curve of The Amino Acids
• At its PI a molecule stops migrating in an electric field
• The PI of amino acid may be determined by the following
equation
• PI = I/2 (pKa1 + pKa2)____ __
The Peptide Bond
• Amino acids can be linked together by covalent bonds
• The bonds are formed between the -carboxyl group of
one amino acid and the -amino group of the next one
• Water is removed in the process and the linked amino
residues remain attached to one another
• This bond is called a peptide bond and peptides are formed
• When hundreds of amino acids are joined in this process, a
polypeptide is formed
• The compound formed may also be referred to as an amide
• The bond formed between the carbon and nitrogen is a
single bond
The Peptide Bond
The Peptide Bond
The Peptide Bond
• One pair of electrons is shared between the two atoms
• With a shift in the position of the electrons, the bond can
be written as a double bond
• This shifting of electrons results in resonance structure
• These are structures that differ in the position of the
electrons
• The positions of double and single bond in one resonance
structure are different from their position in another
resonance structure of the same compound
• Thus the peptide bond can be written as a hybrid of two
structures, one with a single bond between carbon and
nitrogen and the other with a double bond
The Peptide Bond
• The resonance structures of the peptide bond lead to a
planar amide group
The Peptide Bond
• The peptide bond has partial double bond characteristic
Therefore the peptide group that forms link between the
two amino acids in planar
• As a result of the resonance stabilization, the peptide bond
is stronger than an ordinary single bond
• There is free rotation around the bonds between the carbon of a given amino acid residue and the amino
nitrogen and carbonyl carbon of that residue
• However there is no significant rotation around the peptide
bond
• This stereochemistry is important in determining how the
protein backbone folds
Some Small Peptides of Physiological
Interest
• Simplest combination of amino acids are dipeptides in
which two amino acids are linked together
• An example is the dipeptide carnosine which is found in
muscle tissue
• The compound is also known as -alanyl-L-histidine
• The peptide bond is formed between the carboxyl group of
the -alanine and the amino group of histidine
• Aspartame is another dipeptide which has health
implications
• Glutathione a tripeptide is a scavenger for oxidizing agents
The Peptide Bond
• Glutathione is -glutamyl-L-cystenylglycine
• Two pentapeptides found in the brain are enkaphalins
which are natural analgesics
– Tyr-Gly-Gly-Phe-Leu (leucine enkaphalin)
– Tyr-Gly-Gly-Phe-Met (Methionine enkaphalin)
• Opiates bind to the same receptors in the brain intended for
the enkaphalins and hence produce their physiological
activities
• Oxytocin and vasopressin have cyclic structures
• Each has 9 amino acid residues and an amide group at the
C-terminal and disulfide bonds at positions 1 and 6
The Peptide Bond
• Peptide bonds form the cyclic structure in some peptides
• Gramicidin S and tyrocidine A are antibiotic that contain D
amino acids as well as L amino acids
• They both also contain the amino acid ornithine which
does not occur in proteins but plays a role in metabolic
intermediate several common pathways
References
• 1. Biochemistry, Campbell/Farrel 3rd Edition
• 2. Fundamentals of Biochemistry, Voet D, Voet JG, Pratt
CW
• 3. Biochemistry, Mathews/van Holde 2nd Edition