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AMINO ACIDS, PEPTIDES, AND PROTEINS
REVIEW
(I) Carboxylic Acid
y Properties of Carboxylic Acid In aqueous solution, carboxylic acid is in equilibrium with carboxylate ion whose negative
charge is delocalized over two equivalent oxygen atoms (resonance). p.755
Generally,
In acidic solution at low pH, carboxylic acid is almost completely undissociated and exists
almost entirely as RCO2H. p.758
In basic solution at high pH, carboxylic acid is almost completely dissociated and exists
almost entirely as RCO2-. p.758
At physiological pH of 7.3 , carboxylic acids are mostly dissociated. p.758
[See appendix for acidity of some common carboxylic acids.]
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y Substituent Effects on Acidity of Carboxylic AcidsBecause the dissociation of carboxylic acid is an equilibrium process, any factor that
stabilizes the carboyxlate anion will drive equilibrium to the right and result in increased
acidity. p.759
For example,
[Note: chlorine is an electron-withdrawing atom.]
(II) Amines
Amines are derivatives of ammonia, wherein one or more hydrogen atoms have been
replaced by a substituent such as an alkyl or aryl group.
http://en.wikipedia.org/wiki/Amine
Heterocylic amines, compounds in which the nitrogen at om occurs as part of a ring, are
common. p.918
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y Properties of Amines Amines contain a nitrogen atom with a lone pair of electrons, making amines both basic and
nucleophilic. p.916
In aqueous solution, equilibrium is established in which water acts as an acid and transfers a
proton to the amine. p.921
[See appendix for basicity of some common amines.]
Generally,
In acidic solution at low pH , almost all amines are protonated. p.927
In basic solution at high pH , almost all amines are unprotonated. p.927
At physiological pH of 7.3 , amines are mostly protonated. p.927
y ArylaminesArylamines are generally less basic than alkylamines due to resonance. p.924
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idin
e
y
es
y
es are
as
c
as s
rong as alkylamines
p.949
(pKa = 5.25
i
!idin
: It is weakly basic (due to inductivee
ect of thesecond nitrogen). p.950
"
# # #
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& '
tion of C&
box
li'
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id with A!
in
Since amines are basic and carboxylic acid groups are acidic we have an acid and base
reaction.
RNH2 + RCOOH
RNH3+
+ RCO2-
carboxylatesalt
Heating thecarboxylatesalt above100oC will cause dehydration, thus forming amide.The
overall reaction is:
This reaction iscommonly found in living organisms. But instead of producing amide as
shown above, the reaction is facilitated bycomplex enzyme mechanisms.
http://homepage.mac.com/tminehan/spring334pdfs/11&12Bnew.pdf
http://www.mnstate.edu/jasperse/Chem360/Handouts/Ch%2019%20Reactions%20%28p%
201-6%29.pdf
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(
)V
0
A1
id2
s
Amides (RCONH2) are nonbasic and are poor nucleophiles, unlike amines. This is because
amides are hybrids of two resonance forms. p.922
(
V0
3
hiols
Thiols arecompounds having thestructure RSH where R H.
http://goldbook.iupac.org/T06359.html
Thiolscan be oxidized (ie. byBr2 or I2) to yield disulfides (RSSR). The reaction iseasily
reversed, and a disulfidecan be reduced (ie. by zinc and acid) back to a thiol.p.668
[Advanced: In cells the oxidizing agent can be H2O2 and the reducing agent can beFADH2.]
A4 )
N5
AC) 6
7
A1
ino8 9
ids are moleculescontaining an amino group, carboxyl group, sidechain and
hydrogen attached to thecentral carbon. They are difunctional as theycontain both a
carboxyl group (acidic) and an amino group (basic).
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Recall that at physiological pH of 7.3, carboxyl group is deprotonated while amino group is
protonated. Thus, amino acids exist in aqueous solution primarily in the form of a diplor ion,
also called z@
itterion.
A zwitterions is a compound with no overall electrical charge, but contains separate partswhich are positively and negatively charged.
Amino acid zwitterions are internal salts and therefore have many of the physical properties
associated with salts. They are soluble in water but insoluble in hydrocarbons. p.1017
--------------------
Amino acids are also amphiprotic: they can react as acids or as bases, depending on the
circumstances.
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Nearly all proteins in all species are built from the same 20A
- amino acids. They are called
alpha amino acids because the amine is attached to the carbon in the alpha position to the
carbonyl. In humans, ten of the amino acids are essential. In other words the body cannot
manufacture these 10, so they must be ingested directly.
Nineteen of the twenty amino acids are primary amines, RHN2, and differ only in the nature
of the side chain attached to theB
carbon. Proline is a secondary amine and the only
amino acid whose nitrogen and E carbon atoms are part of a ring.
Except for glycine, H2NCH2COOH, the E carbons of amino acids are chirality centers. Two
enantiomers of each are therefore possible, but nature uses only one to build proteins. The
naturally occurring E - amino acids are often referred to as L amino acids. The nonnaturally
occurring enantiomers are called Damino acids.
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CLASSIFICATION OF AMINO ACIDS
The 20 common amino acids can be further classified as neutral, acidic or basic, depending
on the structure of their side chains. Fifteen of the t wenty have neutral side chains, two
(aspartic acid and glutamic acid) have an extra carboxylic acid function in their side chains,
and three (lysine, arginine, and histidine) have basic amino groups in their side chains. Note
that both cysteine and tyrosine, although usually classified as neutral, nevertheless have
weakly acidic side chains that can be deprotonated in a sufficiently basic solution.
At physiological pH of 7.3, the side-chain carboxyl groups of aspartic acid and glutamic acid
are deprotonated and the basic side-chain nitrogens of lysine and arginine are protonated.
Histidine, however, which contains a heterocyclic imidazole ring in its side chain, is not quite
basic enough to be protonated at pH 7.3. Note that only the pyridine -like doubly bonded
nitrogen in histidine is basic. The other is nonbasic because its lone pair of electrons forms
part of the aromaticity.
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Amino acids may also be classified as polar or non-polar according to their side chains. See
below. (For details, see appendix)
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ISOELECTRIC POINTS
In acid solution, an amino acid is protonated and exists primarily as a cation. In basic
solution, an amino acid is deprotonated and exists primarily as an anion.
The isoelectric point of an amino acid is the pH value at which the amino acid is exactly
balanced between anionic and cationic forms. The ioselectric point is dependent on the
structure of the amino acid. In particular, the side chain of the amino acid determines theisoelectric point.
We can take advantage of the differences in isoelectric points to separate a mixture of
amino acids. Using a technique known as electrophoresis , a mixture of amino acids is placed
near the center of a strip of paper or gel. The paper or gel is moistened with an aqueous
buffer of a given pH, and electrodes are connected to the ends of the strip. When an electric
potential is applied, those amino acids with negative charges (those that are deprotonated
because the pH of the buffer is above their isoelectric poin t) migrate slowly toward the
positive electrode. At the same time, those amino acids with positive charges (those that
are protonated because the pH of the buffer is below their isoelectric point) migrate toward
the negative electrode.
Different amino acids migrate at different rates, depending on their isoelectric points and on
the pH of the aqueous buffer, thereby separating the mixture.
[Note: the separated amino acids are made visible by spraying with ninhydrin.]
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POLYPEPTIDES AND PROTEINS
In nature, individual amino acids are linked together in chains as polypeptides and proteins.
The amino acids found in polypeptides or proteins are known as residues.
The diagrams below show the condensation of the amino acids alanine and serine to form a
depeptide. The amino acids are bonded together by a peptide link (amide bond) .
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Each peptide link forms:
y between the carboxyl group and an amino groupy with loss of a water moleculeFurther condensation reactions between amino acids build up a polypeptide or protein.
y For each amino acid added to a protein chain, one water molecule is lost.y Most common proteins contain more than 100 amino acids.The long, repetitive sequence of -N-CH-CO- atoms that make up a continuous chain is called
the proteins backbone. By convention, peptides are written with the N-terminal amino
acid (the one with the free -NH2 group) on the left and the C-terminal amino acid (the one
with the free -CO2H group) on the right.
The amide bond that links different amino acids together in peptides is no different from
any other amide bond. Amide nitrogens are nonbasic because their unshared electron pair
is delocalized by interaction with carbonyl group.
Hydrolysis breaks down a protein into its separate amino acids. For example,
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A second kind of covalent bonding in peptides occurs when a disulfide linkage, RS -SR, is
formed between two cysteine residues. A disulfide is formed by mild oxidation of a th iol,
RSH, and is cleaved by mild reduction.
A disulfide bond between cysteine residues in different peptide chains links the otherwise
separate chains together, while a disulfide bond between cysteine residues in the same
chain forms a loop.
PROTEIN STRUCTURE
Proteins are usually classified as either fibrous or globular, according to their three-dimensional shape. Fibrous proteins, such as the collagent in tendons and connective tissue
and the myosin in muscle tissueee, consists of polypeptid e chainsss arranged side by side in
long filaments. Because these proteins are tough and insoluble in water, they are used in
nature of structural materials. Globular proteins , by contrast, are usually coled into
compact, roughly spherical shapes. These proteins are generally soluble in water and are
mobile within cells.Most of the 3000 or so enzymes that have been characterized to date
are globular proteins.
Proteins are so large that the word structure takes on a broader meaning than it does with
simpler organic compounds. In fact, chemists speak of four different levels of structure
when describing proteins:
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Primary Structure
The primary structure of a protein is the actual sequence of amino acidsjoined by peptide
links.
eg. ala-gly-lys-cys-asn-arg-gly-leu-try-val..
Secondary Structure
The secondary structure of a protein is a region in which there are regular structures. There
are two types, an E -helix and a F -sheet, each held together by hydrogen bonds between
C=O and N-H.
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Tertiary Structure
The tertiary structure refers to the three dimensional shape formed when the peptide chain
curls and folds. Five forces create the tertiary structure.
(1) covalent disulfide bonds between two cysteine amino acids on different part of the
chain;
(2) electrostatic (ionic) interactions mostly between acidic and basic side chains such as -
CH2COO-
and NH3+;
(3) hydrogen bonds between polar side chains such as C H2OH and CH2CONH2;
(4) Van der Waals forces;
(5) hydrophobic side chains pushed away from water (toward the center) of protein.
Quaternary Structure
When two or more polypeptide chians bind together, they form the quaternary structure of
the protein. The same five forces at work in the tertiary structure can also act to form the
quaternary structure.
-------------------
When the conformation is disrupted, the protein is said to be denatured. A denaturedprotein has lost most of its secondary, tertiar y, and quaternary structure. Denaturation is
accompanied by changes in both physical and biological properties. Solubility is drastically
decreased (usually).Most enzymes also lose all catalytic activity when denatured, since a
precisely defined tertiary structure is required for their action. Although most denaturation
is irreversible, cases are also known where spontaneous renaturation of an unfolded protein
to its stable tertiary structure occurs. Renaturation is accompanied by a full recovery of
biological activity.
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APPENDIX
p.756
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p.923
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