Download OC 27 Amino Acids

27
Organic
Chemistry
William H. Brown &
Christopher S. Foote
27-1
27
Amino Acids
& Proteins
Chapter 27
27-2
27 Amino Acids
 Amino
acid: a compound that contains both an
amino group and a carboxyl group
• -Amino acid: an amino acid in which the amino
group is on the carbon adjacent to the carboxyl group
• although -amino acids are commonly written in the
unionized form, they are more properly written in the
zwitterion (internal salt) form
O
RCHCOH
NH2
O
RCHCONH3
+
27-3
27 Chirality of Amino Acids
 With
the exception of glycine, all protein-derived
amino acids have at least one stereocenter (the
-carbon) and are chiral
• the vast majority have the L-configuration at their carbon
COOH
N H3 +
CH3
D-Alanine
COOH 3N
H
CH3
L-Alanine
27-4
27 Nonpolar side chains
COO- Alanine
(Ala, A)
N H3 +
COO- Phenylalanine
(Phe, F)
+
N H3
COO- Glycine
(Gly, G)
N H3 +
COO- Isoleucine
(Ile, I)
N H3 +
-
COO
N H3 +
S
Leucine
(Leu, L)
COO- Methionine
(Met, M)
N H3 +
N
H
N
H
COO- Proline
(Pro, P)
H
COO- Tryptophan
(Trp, W)
N H3 +
COO- Valine
(Val, V)
N H3 +
27-5
27 Polar side chains
COO-
H 2N
O
N H3 +
Asparagine
(Asn, N)
O
H 2N
COO- Glutamine
(Gln, Q)
N H3 +
HO
COO-
Serine
(Ser, S)
N H3 +
OH
COO- Threonine
(Thr, T)
N H3 +
27-6
27 Acidic & basic side chains
-
COO-
O
O
N H3
+
Aspartic acid
(Asp, D)
N H2 +
H 2N
O
-
COO-
O
N H3
+
Glutamic acid
(Glu, E)
N
H
3
N
-
HS
COO
N H3 +
Cysteine
(Cys, C)
-
COO
HO
N H3 +
Tyrosine
(Tyr, Y)
N
H
+
H 3N
COO- Arginine
(Arg, R)
NH +
COON H3
+
COON H3 +
Histidine
(His, H)
Lysine
(Lys, K)
27-7
27 Other Amino Acids
O
-
+
H 3N
COO
H 2N
N H3 +
N
H
L-Ornithine
I
HO
N H3 +
L-Citrulline
I
O
I
COO-
CH2 CHCOO
I
L-Thyroxine, T4
O
-
N H3
+
-
O
N H3 +
4-Aminobutanoic acid
(-Aminobutyric acid, GABA)
27-8
27
AcidBase
Properties
Nonpolar &
polar side
chains
alanine
asparagine
glutamine
glycine
isoleucine
leucine
methionine
phenylalanine
proline
serine
threonine
tryptophan
valine
pK a of
pK a of
COOH
2.35
2.02
2.17
2.35
2.32
2.33
2.28
2.58
2.00
2.21
2.09
2.38
2.29
NH3
9.87
8.80
9.13
9.78
9.76
9.74
9.21
9.24
10.60
9.15
9.10
9.39
9.72
+
27-9
27 Acid-Base Properties
Acidic
pKa of
pKa of
Side
+
COOH
NH
Chains
3
aspartic acid
2.10
9.82
glutamic acid
2.10
9.47
cysteine
2.05
10.25
tyrosine
2.20
9.11
pKa of
Side
Chain
3.86
4.07
8.00
10.07
Side
Chain
Group
carboxyl
carboxyl
sufhydryl
phenolic
Basic
Side
Chains
arginine
histidine
lysine
pKa of
Side
Chain
12.48
6.10
10.53
Side
Chain
Group
guanidino
imidazole
1° amino
pKa of
pKa of
COOH NH3
2.01
9.04
1.77
9.18
2.18
8.95
+
27-10
27 Acidity: -CO2H Groups
average pKa of an -carboxyl group is 2.19,
which makes them considerably stronger acids
than acetic acid (pKa 4.76)
 The
• the greater acidity is accounted for by the electronwithdrawing inductive effect of the adjacent -NH3+
group
RCHCOOH + H2 O
N H3
+
+
RCHCOO + H3 O
N H3
pKa = 2.19
+
27-11
27 Acidity: side chain -COOH
 Due
to the electron-withdrawing inductive effect
of the -NH3+ group, side chain -COOH groups
are also stronger than acetic acid
• the effect decreases with distance from the -NH3+
group. Compare:
-COOH group of alanine (pKa 2.35)
-COOH group of aspartic acid (pKa 3.86)
-COOH group of glutamic acid (pKa 4.07)
27-12
27 Acidity: -NH3+ groups
average value of pKa for an -NH3+ group is
9.47, compared with a value of 10.76 for a 1°
alkylammonium ion
 The
RCHCOO + H2 O
N H3
+
pKa = 9.47
N H2
CH3 CHCH 3 + H2 O
N H3
+
RCHCOO + H3 O
+
CH3 CHCH 3 + H3 O
+
pKa = 10.60
N H2
27-13
27 Basicity-Guanidine Group
• basicity of the guanidine group is attributed to the
large resonance stabilization of the protonated form
relative to the neutral form
N H2
+
:
:
N H2
+
RN H C
:
:
N H2
RN H C
RN H C
+
N H2
N H2
:
:
N H2
H2 O
:
N H2
+ H3 O
RN C
+
pKa = 12.48
:
N H2
27-14
27 Basicity- Imidazole Group
• the imidazole group is a heterocyclic aromatic amine
H
H
••
N
N H3
N+
H
+
N
+
-
COO
Not a part of the
aromatic sextet;
the proton acceptor
••
N
N H3 +
-
COO
H2O
H3O+
H
••
N
••
N
H
N H3 +
+
COO- + H3O
pKa 6.10
27-15
27 Ionization vs pH
 Given
the value of pKa of each functional group,
we can calculate the ratio of each acid to its
conjugate base as a function of pH
• consider the ionization of an -COOH
• writing the acid ionization constant and rearranging
terms gives
COOH + H2 O
Ka =
pKa = 2.00
[ H3 O+ ] [-COO- ]
[-COOH
or
-
+ H3 O+
COO
[-COO-]
[ -COOH
=
Ka
[ H3 O+ ]
27-16
27 Ionization vs pH
• substituting the value of pKa (2.00) for the hydrogen
ion concentration at pH 7.0 (1.0 x 10-7) gives
-
[-COO ]
[ -COOH
=
Ka
+
[ H3 O ]
=
1.00 x 10-2
1.00 x 10-7
= 1.00 x 105
• at pH 7.0, the -carboxyl group is virtually 100% in the
ionized form and has a net charge of -1
• we can repeat this calculation at any pH and
determine the ratio of [-COO-] to [-COOH] and the
net charge on the -carboxyl at that pH
27-17
27 Ionization vs pH
 We
can also calculate the ratios of acid to
conjugate base for an -NH3+ group; for this
calculation, assume a value 10.0 for pKa
• writing the acid ionization constant and rearranging
gives
NH3
+
+ H2 O
pK a = 10.00
[ -NH2 ]
[-NH3 + ]
=
NH2
+ H3 O+
Ka
[H3 O+ ]
27-18
27 Ionization vs pH
• substituting values for pKa of an -NH3+ group and
the hydrogen ion concentration at pH 7.0 gives
[-NH2 ]
[ -NH3 ]
+
Ka
=
[ H3 O+ ]
=
1.00 x 10-1 0
-7
1.00 x 10
= 1.00 x 10-3
• thus at p H 7.0, the ratio of -NH3+ to -NH2 is
approximately 1 to 1000
• at this pH, an -amino group is 99.9% in the
protonated form and has a charge of +1
27-19
27 Henderson-Hasselbalch
• for the ionization of any weak acid HA
HA + H2 O
A- + H3 O+
Ka =
[A-][H3 O+]
[HA]
• taking the log and rearranging gives
-log [H3O+ ] = -log Ka + log
[A-]
[HA]
• substitution pH and pKa gives the HendersonHasselbalch equation
[A-]
pH = pKa + log
[HA]
27-20
27 Henderson-Hasselbalch
• using the Henderson-Hasselbalch equation
[A-]
pH = pKa + log
[HA]
we see that
• when pH = pKa, the concentrations of weak acid and
its conjugate base are equal
• when pH < pKa, the weak acid predominates
• when pH > pKa, the conjugate base predominates
27-21
27 Isoelectric Point
 Isoelectric
point, pI, of an amino acid: the pH at
which the majority of its molecules in solution
have no net charge
• the pH for glycine, for example, falls between the pKa
values for the carboxyl and amino groups
+
1
pI = 2 ( pKa COOH + pKa NH3 )
= 1 (2.35 + 9.78) = 6.06
2
27-22
27
Nonpolar &
pK a of
pK a of
polar side
+
COOH
NH
chains
3
alanine
2.35
9.87
asparagine
2.02
8.80
glutamine
2.17
9.13
glycine
2.35
9.78
isoleucine
2.32
9.76
leucine
2.33
9.74
methionine
2.28
9.21
phenylalanine 2.58
9.24
proline
2.00
10.60
serine
2.21
9.15
threonine
2.09
9.10
tryptophan
2.38
9.39
valine
2.29
9.72
pK a of
Side
Chain
----------------------------------------
pI
6.11
5.41
5.65
6.06
6.04
6.04
5.74
5.91
6.30
5.68
5.60
5.88
6.00
27-23
27
Acidic
Side Chains
aspartic acid
glutamic acid
cysteine
tyrosine
Basic
Side Chains
arginine
histidine
lysine
pK a of
+ Side
COOH NH3 Chain
2.10
9.82
3.86
2.10
9.47
4.07
2.05
10.25
8.00
2.20
9.11
10.07
2.98
3.08
5.02
5.63
pK a of
+ Side
COOH NH3 Chain
2.01
9.04
12.48
1.77
9.18
6.10
2.18
8.95
10.53
pI
10.76
7.64
9.74
pK a of
pK a of
pK a of
pI
pK a of
27-24
27 Electrophoresis
 Electrophoresis:
the process of separating
compounds on the basis of their electric charge
• electrophoresis of amino acids can be carried out
using paper, starch, agar, certain plastics, and
cellulose acetate as solid supports
 In
paper electrophoresis
• a paper strip saturated with an aqueous buffer of
predetermined pH serves as a bridge between two
electrode vessels
27-25
27 Electrophoresis
• a sample of amino acids is applied as a spot on the
paper strip
• an electric potential is applied to the electrode
vessels and amino acids migrate toward the electrode
with charge opposite their own
• molecules with a high charge density move faster
than those with low charge density
• molecules at their isoelectric point remain at the
origin
• after separation is complete, the strip is dried and
developed to make the separated amino acids visible
27-26
27 Electrophoresis
• a reagent commonly used to detect amino acid is
ninhydrin
O
O
RCHCO + 2
N H3
OH
OH
+
O
Ninhydrin
An -amino
acid
O
O
-
N
O
+ RCH + CO 2 + H3 O +
O
O
Purple-colored anion
27-27
27 Polypeptides & Proteins
 In
1902, Emil Fischer proposed that proteins are
long chains of amino acids joined by amide
bonds to which he gave the name peptide bonds
 Peptide bond: the special name given to the
amide bond between the -carboxyl group of
one amino acid and the -amino group of
another
27-28
27 Serylalanine (Ser-Ala)
HOCH2 H
H2 N
O
O
O
Serine
(Ser, S)
H
+
H2 N
O
H
H CH3
Alanine
(Ala, A)
peptide bond
HOCH2 H H
O
N
H
H2 N
O
O H CH3
Serylalanine
(Ser-Ala, (S-A)
27-29
27 Peptides
• peptide: the name given to a short polymer of amino
acids joined by peptide bonds; they are classified by
the number of amino acids in the chain
• dipeptide: a molecule containing two amino acids
joined by a peptide bond
• tripeptide: a molecule containing three amino acids
joined by peptide bonds
• polypeptide: a macromolecule containing many
amino acids joined by peptide bonds
• protein: a biological macromolecule of molecular
weight 5000 g/mol of greater, consisting of one or
more polypeptide chains
27-30
27 Writing Peptides
• by convention, peptides are written from the left,
beginning with the free -NH3+ group and ending with
the free -COO- group on the right
+
H 3N
N-terminal
amino acid
O
C6 H5
O
H
N
C-terminal
amino acid
N
OH
O
OH
COOSer-Phe-Asp
27-31
27 Primary Structure
 Primary
structure: the sequence of amino acids
in a polypeptide chain; read from the Nterminal amino acid to the C-terminal amino acid
 Amino acid analysis
• hydrolysis of the polypeptide, most commonly carried
out using 6M HCl at elevated temperature
• quantitative analysis of the hydrolysate by ionexchange chromatography
27-32
27 Cyanogen Bromide, BrCN
• cleavage of peptide bonds formed by the carboxyl
group of methionine
cyanogen bromide is
specific for the cleavage
of this peptide bond
from the
N-terminal
end
O
O
from the
C-terminal end
P N-C-N H CH C N H-P C
CH2
CH2 -S-CH3
27-33
27 Cyanogen Bromide, BrCN
O
HN pe pt id e COOH3 N pe pt id e C-N H
O
+ Br C N
side chain
of methionine
0.1 M HCl
H2 O
S- CH3
O
H3 N pe pt id e C-N H
O
O
A substituted -lactone of
the amino acid homoserine
H 3 N pe pt id e COO-
CH3 S- C N
Methyl
thiocyanate
27-34
27 Cyanogen Bromide, BrCN
• Step 1: nucleophilic displacement of bromine
H3 N
O
HN
C-N H
COOO
H3 N
O
HN
C-N H
COOO
Br
:
: S- CH3
Br
C N
Cyanogen bromide
a sulfonium
ion; a good
leaving group
-
: S- CH3
C N
27-35
27 Cyanogen Bromide, BrCN
• Step 2: internal nucleophilic displacement
H3N
C-NH
:
O
COO-
HN
O
O
: S-CH3
C N
H3N
C-NH
HN
COO-
:
An iminolactone
hydrobromide
+ CH3-S-C N
:
O
Methyl
thiocyanate
27-36
27 Cyanogen Bromide, BrCN
• Step 3: hydrolysis of the imino group
O
H3 N
C-N H
HN
COOH2 O
O
O
H3 N
C-N H
O
O
H 3N
COO-
A substituted -lactone of
the amino acid homoserine
27-37
27 Enzyme Catalysis
A
group of protein-cleaving enzymes can be
used to catalyze the hydrolysis of specific
peptide bonds
Enzyme
Catalyzes Hydrolysis of Peptide Bond
Formed by Carboxyl Group of
Trypsin
Arginine, lysine
Chymotrypsin Phenylalanine, tyrosine, tryptophan
27-38
27 Edman Degradation
 Edman
degradation: cleaves the N-terminal
amino acid of a polypeptide chain
N-terminal
amino acid
R
+
H 3N
NH
O
COO-
+ S= C= N -Ph
Phenyl isothiocyanate
R
HN
S
O + H2 N
COO-
N
Ph
A phenylthiohydantoin
27-39
27 Edman Degradation
• Step 1: nucleophilic addition to the C=N group of
phenylisothiocyanate
R
NH
:
H 2N
O
O
HN
:
:
Ph N C S
R
COO-
Ph N
H
S
NH
COO-
A derivative of
N-phenylthiourea
27-40
27 Edman Degradation
• Step 2: nucleophilic addition of sulfur to the C=O of
the adjacent amide group
R
HN
Ph N
H
O+
R
O–H
HN
NH
COOH
S
+
Ph-N
H
H
S
NH
+
H
COOH
H+
R
HN
O
Ph-N
+
+ H 3N
COOH
S
A thiazolinone
27-41
27 Edman Degradation
• Step 3: isomerization of the thiazolinone ring
R
R
HN
O
Ph-N
S
A thiazolinone
+ H-Nu
O
HN
S
NH
- H-Nu
Nu
Ph
R
HN
O
S
N
Ph
A phenylthiohydantoin
27-42
27 Primary Structure
Example 27.8 Deduce the 1° structure of this
pentapeptide
Experimental Procedure
pentapeptide
Edman Degradation
Hydrolysis - Chymotrypsin
Fragment A
Fragment B
Hydrolysis - Trypsin
Fragment C
Fragment D
Amino Acid Composition
Arg, Glu, His, Phe, Ser
Glu
Glu, His, Phe
Arg, Ser
Arg, Glu, His, Phe
Ser
27-43
27 Polypeptide Synthesis
problem is join the -carboxyl group of aa1 by an amide bond to the -amino group of aa2, and not vice versa
 The
O
O
+
+
H3 NCHCO + H3 NCHCO
aa2
aa1
?
O
O
+
H3 NCHCNHCHCO + H2 O
aa1
aa2
27-44
27 Polypeptide Synthesis
• protect the -amino group of aa-1
• activate the -carboxyl group of aa-1
• protect the -carboxyl group of aa-2
protecting
group
activating
group
O
protecting
group
O
Z-N HCHC- Y + H2 N CH C-X
a a2
a a1
form peptide
bond
O
O
Z-N HCHCN HCHC-X + H- Y
a a1
a a2
27-45
27 Amino-Protecting Groups
• the most common strategy for protecting amino
groups and reducing their nucleophilicity is to
convert them to amides
O
PhCH2 OCCl
Benzyloxycarbonyl
chloride
O O
( CH3 ) 3 COCOCOC(CH3 ) 3
Di-tert-butyl dicarbonate
O
PhCH2 OCBenzyloxycarbonyl
(Z-) group
O
(CH3 ) 3 COCtert-Butoxycarbonyl
(BOC-) group
27-46
27 Amino-Protecting Groups
• treatment of an amino group with either of these
reagents gives a carbamate (an ester of the
monoamide of carbonic acid)
O
+
- 1 . Na OH
PhCH2 OCCl + H3 NCHCO
2 . HCl, H2 O
CH3
Benzyloxycarbonyl
Alanine
chloride
O
O
(Z-Cl)
PhCH2 OCN HCHCOH
O
CH3
N-Benzyloxycarbonylalanine
(Z-ala)
27-47
27 Amino-Protecting Groups
• a carbamate is stable to dilute base but can be
removed by treatment with HBr in acetic acid
O
PhCH2 OCN H-peptide
A Z-protected peptide
HBr
CH3 COOH
+
PhCH2 Br + CO 2 + H3 N- peptide
Unprotected
Benzyl
peptide
bromide
27-48
27 Amino-Protecting Groups
 The
benzyloxycarbonyl group is removed by
hydrogenolysis (Section 20.6C)
• the intermediate carbamic acid loses carbon dioxide
to give the unprotected amino group
O
PhCH2 OCN H-p ep t ide + H2
A Z-protected peptide
Pd
PhCH3 + CO 2 + H2 N- pe pt ide
Toluene
Unprotected
peptide
27-49
27 Carboxyl-Protecting Grps
 Carboxyl
groups are most often protected as
methyl, ethyl, or benzyl esters
• methyl and ethyl esters are prepared by Fischer
esterification, and removed by hydrolysis in aqueous
base under mild conditions
• benzyl esters are removed by hydrogenolysis (Sect.
20.6C); they are also removed by treatment with HBr
in acetic acid
27-50
27 Peptide Bond Formation
 The
reagent most commonly used to bring
about peptide bond formation is DCC
• DCC is the anhydride of a disubstituted urea and,
when treated with water, is converted to DCU
N C N
+ H2 O
1,3-Dicyclohexylcarbodiimide
(DCC)
O
N C N
H
H
N,N'-dicyclohexylurea
(DCU)
27-51
27 Peptide Bond Formation
• DCC acts as dehydrating in bringing about formation
of a peptide bond
O
O
CHCl 3
Z-N HCHC- OH + H2 NCHCOCH3 + DCC
R1
R2
Amino-protected Carboxyl-protected
aa1
aa2
O
O
Z-N HCHC- NHCH COCH3 + DCU
R1
R2
Amino and carboxyl
protected dipeptide
27-52
27 Solid-Phase Synthesis
 Bruce
Merrifield, 1984 Nobel prize for Chemistry
• solid support: a type of polystyrene in which about
5% of the phenyl groups carry a -CH2Cl group
• the amino-protected C-terminal amino acid is bonded
as a benzyl ester to the support beads
• the polypeptide chain is then extended one amino
acid at a time from the N-terminal end
• when synthesis is completed, the polypeptide is
released from the support beads by cleavage of the
benzyl ester
27-53
27 Peptide Bond Geometry
• the four atoms of a peptide bond and the two alpha
carbons joined to it lie in a plane with bond angles of
120° about C and N
27-54
27 Peptide Bond Geometry
• to account for this geometry, Linus Pauling proposed
that a peptide bond is most accurately represented as
a hybrid of two contributing structures
• the hybrid has considerable C-N double bond
character and rotation about the peptide bond is
restricted
:
:
-
:O
C
:
C
C
:O :
C
N
H
C
+
C
N
H
27-55
27 Peptide Bond Geometry
• two conformations are possible for a planar peptide
bond
• virtually all peptide bonds in naturally occurring
proteins studied to date have the s-trans
conformation
•
•
C
O
••
H
•
•
••
O
••
C
C
••
N
C
H
s-trans
N
C
C
s-cis
27-56
27 Secondary Structure
 Secondary
structure: the ordered arrangements
(conformations) of amino acids in localized
regions of a polypeptide or protein
 To determine from model building which
conformations would be of greatest stability,
Pauling and Corey assumed that
1. all six atoms of each peptide bond lie in the same
plane and in the s-trans conformation
2. there is hydrogen bonding between the N-H group of
one peptide bond and a C=O group of another peptide
bond as shown in the next screen
27-57
27 Secondary Structure
• hydrogen bonding between amide groups
hydrogen
bonding
27-58
27 Secondary Structure
 On
the basis of model building, Pauling and
Corey proposed that two types of secondary
structure should be particularly stable
• -helix
• antiparallel -pleated sheet
 -Helix:
a type of secondary structure in which a
section of polypeptide chain coils into a spiral,
most commonly a right-handed spiral
27-59
27 The -Helix
 In
a section of -helix
• there are 3.6 amino acids per turn of the helix
• each peptide bond is s-trans and planar
• N-H groups of all peptide bonds point in the same
direction, which is roughly parallel to the axis of the
helix
• C=O groups of all peptide bonds point in the opposite
direction, and also parallel to the axis of the helix
• the C=O group of each peptide bond is hydrogen
bonded to the N-H group of the peptide bond four
amino acid units away from it
• all R- groups point outward from the helix
27-60
27 The -Helix
27-61
27 -Pleated Sheet
antiparallel -pleated sheet consists of
adjacent polypeptide chains running in opposite
directions
 The
• each peptide bond is planar and has the s-trans
conformation
• the C=O and N-H groups of peptide bonds from
adjacent chains point toward each other and are in
the same plane so that hydrogen bonding is possible
between them
• all R- groups on any one chain alternate, first above,
then below the plane of the sheet, etc.
27-62
27 Tertiary Structure
 Tertiary
structure: the three-dimensional
arrangement in space of all atoms in a single
polypeptide chain
• disulfide bonds between the side chains of cysteine
play an important role in maintaining 3° structure
H
N
side chains
of cysteine
N
H
O
N
H
SH
SH
H
N
O
H
N
O
N
H
oxidation
S
reduction
S
N
H
a disulfide
bond
H
N
O
27-63
27 Quaternary Structure
 Quaternary
structure: the arrangement of
polypeptide chains into a noncovalently bonded
aggregation
• the major factor stabilizing quaternary structure is the
hydrophobic effect
 Hydrophobic
effect: the tendency of nonpolar
groups to cluster together in such a way as to
be shielded from contact with an aqueous
environment
27-64
27 Quaternary Structure
• if two polypeptide chains, for example, each have one
hydrophobic patch, each patch can be shielded from
contact with water if the chains form a dimer
Protein
Number of
Subunits
Alcohol dehydrogenase
Aldolase
Hemoglobin
Lactate dehydrogenase
Insulin
Glutamine synthetase
Tobacco mosaic virus
protein disc
2
4
4
4
6
12
17
27-65
27 Prob 27.19
From what amino acid is histamine derived? By what
type of reaction is the precursor amino acid converted
to histamine?
N
Histamine
CH2 CH2 NH 2
N
H
27-66
27 Prob 27.21
From which protein-derived amino acid are
norepinephrine and epinephrine synthesized? What
types of reactions are involved in each biosynthesis?
H OH
(a)
HO
N H2
HO
Norepinephrine
(b)
HO
H OH H
N
CH3
HO
Epinephrine
(Adrenaline)
27-67
27 Prob 27.22
From which amino acid are serotonin and melatonin
derived? What types of reactions are involved in the
biosynthesis of each?
(a) HO
CH2 CH2 NH 2
N
H
Serotonin
(b) CH 3 O
O
CH 2 CH 2 NH CCH 3
N
H
Melatonin
27-68
27 Prob 27.39
Do you expect the modified guanidino group of
cimetidine to be more basic or less basic that the
guanidino group of arginine?
N -CN
H3 C
HN
CH2 SCH 2 CH2 N HCNH CH3
N
Cimetidine
(Tagamet)
27-69
27 Prob 27.40
Draw a structural formula for the product formed by
treating alanine with each reagent.
(a)
O
CCl, ( CH 3 CH 2 ) 3 N
O
(b)
O
(c)
OH
OH
O
CH2 OCCl, N aOH
O O
(d) ( CH 3 ) 3 COCOCOC( CH 3 ) 3 , N aOH
(e) Product (c) + L-Alanine ethyl ester + DCC
(f) Product (d) + L-Alanine ethyl ester + DCC
27-70
27 Prob 27.45
A tetradecapeptide (14 amino acids) gives these
fragments on partial hydrolysis. From this information,
deduce the primary structure of this polypeptide.
Pentapeptide fragments
Tetrapeptide fragments
Phe-Val-Asn-Gln-His
Gln-His-Leu-Cys
His-Leu-Cys-Gly-Ser
His-Leu-Val-Glu
Gly-Ser-His-Leu-Val
Leu-Val-Glu-Ala
27-71
27 Prob 27.48
Name the amino acids in glutathione. What is unusual
about the peptide bond formed by the N-terminal amino
acid?
O
+
H 3N
O
O-
N
H
SH
H
N
O
O-
O
Glutathione
27-72
27 Prob 27.49
Name the amino acids in aspartame. Estimate the
isoelectric point of this dipeptide.
O
-
O
H
N
+
H 3N
O
O
CH3
O
Aspartame
27-73
27 Prob 27.51
Write a structural formula for the product formed by
treating the N-terminal amino acid of a polypeptide chain
with 2,4-dinitrofluorobenzene, and for the derivatized
amino acid formed when the polypeptide chain is
hydrolyzed in acid.
O
O2 N
O
F + H2 NCHCNH CHC-po lyp ep t ide
R1
R2
NO
derivatized
polypeptide
2
2,4-Dinitrofluorobenzene
(N-Terminal end of
a polypeptide chain)
27-74
27
Amino Acids
& Proteins
End of Chapter 27
27-75