Download Chapter 4: Amino Acids General Features of Amino Acids

Chapter 4: Amino Acids
• All peptides and polypeptides are polymers of alpha-amino acids.
ೈқ፦த‫ڀ‬Ԗ੝‫ޑۓ‬ғ౛ϯᏢ੝‫܄‬Ǵ࣬ၨ‫ܭ‬ਡለǵlipidǵpolysaccharideǵೈқ፦
Кၨ৒ܰϩᚆᆶપϯǴ‫ځ‬ύаenzyme‫ޑ‬ғϯϸᔈЀ‫ځ‬੝‫ۓ‬ǴӢԜࣁԐයғϯࣴ
‫ز‬Ьा‫ޑ‬Ҟ኱Ƕ
ਡለ໺ሀᆶ߄ၲ୷Ӣૻ৲‫ޑ‬ᢀ‫ۈۺ‬Ծ1940sǴԶΑှ‫ځ‬໽ϯфૈ‫ۈ‬Ծ1980s.
LipidsӧmembraneᏼҺ‫فޑ‬Յ‫ۈ‬Ծ1960s. Polysaccharide‫ޑ‬ғϯфૈϝӧዴҥϐ
ύǶ
• Are energy metabolites and many of them are essential nutrients.
• Several of the amino acids found in proteins also serve functions
distinct from the formation of peptides and proteins, e.g., tyrosine in the
formation of thyroid hormones or glutamate acting as a neurotransmitter.
Dopamine
Epinephrine
Tyrosin
Tryptophan
General Features of Amino Acids
• D-amino acids in peptides and proteins (excluding proline) consist of a
carboxylic acid (-COOH) and an amino (-NH2) functional group attached to the
same tetrahedral carbon atom.
• Distinct R-groups, that distinguish one amino acid from another, also are
attached to the alpha-carbon (except in the case of glycine where the R-group is
hydrogen).
• The fourth substitution on the tetrahedral a-carbon
of amino acids is hydrogen.
• In physiological condition, both the carboxylic acid
and the amino groups of a-amino acids are
completely ionized.
pK1ჹᔈ‫ܭ‬a-carboxylic acid, ॶӧ2.2ߕ߈Ƕ
pK2ჹᔈ‫ܭ‬a-amino group,ॶௗ߈9.4Ƕ
pKRࣁЍ᜘functional group‫ޑ‬ለᡵ੝‫܄‬Ƕ
೭ᅿӕ‫ڀ‬ለᡵ‫ޑ܄ނ‬ϩηǴᆀϐࣁampholytes
(amphoteric property)
Physical Properties
Similar to ionic compound because of
charged groups of opposite polarity.(ӕ‫ڀ‬
Ԗ҅ॄႝ಻‫ޑ‬ϩηᆀϐࣁzwitterions‫܈‬
dipolar ions)
• The melting point of most amino acids
are near 300 ºCǶ
• More soluble in polar solvents (H2O etc.)
• At pH 7.0, both carboxyl and amino
group are completely ionized.
There are 20 Amino Acids encoded by
codons in the genetic code.
Peptide Bonds
Peptide bond formation is a condensation reaction leading to the polymerization of
amino acids into peptides and proteins.
(Peptide: hormones, neurotransmitters, several antibiotics and antitumor agents)
The presence of the carbonyl group in a
peptide bond allows electron resonance
stabilization to occur such that the peptide
bond exhibits rigidity not unlike the typical C=C- double bond. The peptide bond is,
therefore, said to have partial double-bond
character.
Amino Acid Structure/Function
These 20 AAs can be divided into the above 3 groups (non-polar,
flexible and polar)and then subdivided by their chemical character. I
prefer to divide them based on the R-functional group.
Aliphatic: Gly, Ala, Val, Leu, Ile, Pro
Aromatic: Phe, Tyr, Trp
Polar but uncharged: Ser, Thr, Asn, Gln
Sulfur containing: Cys, Met
Charged: Asp, Glu, His, Lys, Arg
Amino Acid: Aliphatic-R Group
Gly, Ala, Val, Leu, Ile, Pro
Refer to the structure
Amino Acid: Aromatic R-Group
Phe, Tyr, Trp
Refer to the structure
The aromatic R-groups in amino acids absorb ultraviolet light with an
absorbance maximum in the range of 280nm. The ability of proteins to
absorb ultraviolet light is predominantly due to the presence of the
tryptophan which strongly absorbs ultraviolet light.
Amino Acid: Polar but uncharged
Ser, Thr, Asn, Gln
Refer to the structure
Amino Acid: Sulfur containing
Cys, Met
Refer to the structure
Amino Acid: Charged R-Group
Asp, Glu, His, Lys, Arg
Refer to the structure
Uncommon amino acids
• Hydroxylysine,
hydroxyproline - collagen
• Carboxyglutamate - bloodclotting proteins
• Pyroglutamate –
bacteriorhodopsin
• Phosphorylated amino acids
- signaling device
Other uncommon amino acids
Reactions of Amino acids
• Carboxyl groups form amides &
esters
• Amino groups form Schiff bases and
amides
• Side chains show unique reactivities
– Cys residues can form
disulfides and can be easily
alkylated
– Few reactions are specific to a
single kind of side chain
Optical Properties of the Amino Acids
A tetrahedral carbon atom with 4
distinct constituents is said to be
chiral.
Chirality:
Describe the mirror images of a molecule are not superimposable.
These molecules are designated as enantiomers of one another.
(Ңጄ superimposable‫)ۺཷޑ‬
(Ңጄ optical isomersӧ‫ޜ‬໔΢ค
‫᠄ݤ‬ӝ)
Optical Activity
The handedness of a chiral molecule is observable by the ability of a
molecule to rotate the plane of polarized light either to the right
(dextrorotatory, + or d) or to the left (levorotatory, - or l ).
[D ]25
D
observed rotation (degree)
optical path length (dm) X conc.(g.cm-3 )
The physical and chemical properties
of optical isomers are almost
identical except for the optical
activity.
Polarimeter is used to measure the
specific rotation of optical isomer
Why L-D-amino acids?
All of the amino acids in proteins exhibit the same absolute steric
configuration as L-glyceraldehyde. Therefore, they are all L-D-amino
acids.
hydroxyl, aldehyde, CH2OH
amino, carboxyl, R
D-amino acids are never found in proteins, although they exist in
nature. D-amino acids are often found in polypeptide antibiotics.
More about Chiral Molecules
For molecule with more than one chiral center:
N chiral centers has 2n possible stereoisomers and 2n-1 enantiomeric
pairs.
Diastereisomer:
• The optical isomers are not mirror
image of each other.
• The diastereomers are physically
and chemically distinguishable
from one another.
•A solution contained equal amount
of –d and –l isomer is known as
racemic. It is optical inactive.
Chiral molecules but no optical activity?
A molecule which has an internal mirror symmetry plane, is known as
meso compound.
Even though meso compound has either one or more chiral centers,
the molecule does not have enantiometic isomer.
Absolute Configuration
Dilemma: Given a optical isomer, one can not tell whether it’s in –d
or –l form .
ှ،ᒣ‫ݤ‬: ٬Ҕ Cahn-Ingold-Prelog System‫ۓ‬ကoptical isomer
բ‫ݤ‬: The four groups attached to the chiral center are ranked
according to their atomic number.
SH > OH > NH2 > COOH > CHO > CH2OH > C6H5 > CH3 > 2H > 1H
If the first atom in groups are the same, then the rank is based on the
second atom in groups and so on.
W>X>Y>Z
Rotate the molecule so that the lowest priority group (Z) faces
toward you.
The order of the groups WÆXÆY is clockwise, assigned R.
The order of the groups WÆXÆY is counter-clockwise, assigned S.
Absolute Configuration
‫ݙ‬ཀ;!
Ѱკύ‫ޑ‬ణচη‫׫‬৔ӧࡕय़Ǵ‫ځ‬дΟ
ঁი୷‫ࡰޔ‬ҞຎБӛǴԶࡕࡪW > X >
Y > ZБӛ٩໩‫ׇ‬௽ᙯǴ‫ۓ‬рR,‫܈‬S
configuration.
The configuration of a molecule with multiple asymmetric centers can
be described unambiguously.
Spectroscopic Properties
• All amino acids absorb in infrared region
• Only Phe, Tyr, and Trp absorb UV
• Absorbance at 280 nm is a good diagnostic
device for amino acids
• NMR spectra are characteristic of each residue in
a protein, and high resolution NMR
measurements can be used to elucidate threedimensional structures of proteins
UV spectrum
Superimposible‫ۺཷޑ‬
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ᗨฅchemical formulaϷϩηໆ࣬ӕǴՠࢂ೭‫ঁٿ‬ϩη‫ޜ‬໔΢‫ޑ‬ᄬ‫׎‬
όӕ(Ӣࣁค‫ݤ‬ख़᠄)Ǵ‫܌‬аϩηԄ࣬ӕǴՠࠅࢂ‫ঁٿ‬όӕ‫ޑ‬ϩηǶ
Illustration of the chiral molecule
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ୃཱུӀ࿶ၸoptical isomers཮ౢғୃӀਏ݀
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