27-1 amino acids & proteins. 27-2 amino acids amino acid: amino acid: a compound that contains...
TRANSCRIPT
27-27-11
Amino Acids Amino Acids
& Proteins& Proteins
27-27-22
Amino AcidsAmino Acids
Amino acid:Amino acid: A compound that contains both an amino group and a carboxyl group.• -Amino acid:-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 zwitterionzwitterion (internal salt) form.
RCHCOH
NH2
RCHCO-
NH3+
-Amino Acid Zwitterion form
OO
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Chirality of Amino AcidsChirality 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.
COO-
CH3
HH3N
L-Alanine
COO-
CH3
H NH3+
D-Alanine
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Amino Acids with Nonpolar side chainsAmino Acids with Nonpolar side chains
NH3+
COO-
NH3+
COO-
NH3+
COO-
NH3+
COO-
NH3+
COO-S
NH3+
COO-
NH H
COO-
NH3+
COO-
NH
COO-
NH3+
Alanine (Ala, A)
Glycine (Gly, G)
Isoleucine (Ile, I)
Leucine (Leu, L)
Methionine (Met, M)
Phenylalanine (Phe, F)
Proline (Pro, P)
Tryptophan (Trp, W)
Valine (Val, V)
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With Polar side chainsWith Polar side chains
NH3+
COO-H2N
O
NH3+
COO-H2N
O
NH3+
COO-HO
NH3+
COO-OH
Asparagine (Asn, N)
Glutamine (Gln, Q)
Serine (Ser, S)
Threonine (Thr, T)
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With Acidic & Basic Side ChainsWith Acidic & Basic Side Chains
NH3+
COO--O
O
NH3+
COO--O
O
NH3+
COO-HS
NH3+
COO-
HO
NH3+
COO-NH
H2N
NH2+
NH3+
COO-N
NH
NH3+
COO-H3N
Cysteine (Cys, C)
Tyrosine (Tyr, Y)
Glutamic acid (Glu, E)
Aspartic acid (Asp, D)
Histidine (His, H)
Lysine (Lys, K)
Arginine (Arg, R)
+
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Acid-Base properties, Acid-Base properties, Non polar and polar side chainsNon polar and polar side chains
pKa ofpKa of
valine 2.29 9.72tryptophan 2.38 9.39
9.102.09threonineserine 2.21 9.15
10.602.00prolinephenylalanine 2.58 9.24
9.212.28methionine9.742.33leucine
isoleucine 2.32 9.76glycine 2.35 9.78
9.132.17glutamine8.802.02asparagine9.872.35alanine
Nonpolar &polar side chains NH3
+ COOH
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Acid-Base Properties, Acidic/Basic Side ChainsAcid-Base Properties, Acidic/Basic Side Chains
pKa ofpKa ofpKa of
10.079.112.20tyrosine
lysine 2.18 8.95 10.536.109.181.77histidine
glutamic acid 2.10 9.47 4.078.0010.252.05cysteine
aspartic acid 2.10 9.82 3.86
arginine 2.01 9.04 12.48
Side Chain
AcidicSide Chains NH3
+COOH
pKa ofpKa ofpKa ofSide Chain
BasicSide Chains NH3
+COOH
carboxylcarboxylsufhydrylphenolic
guanidinoimidazole1° amino
SideChainGroup
SideChainGroup
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Acidity: Acidity: -COOH Groups -COOH Groups
The average pKa of an -carboxyl group is 2.19, which makes them considerably stronger acids than acetic acid (pKa 4.76).• The greater acidity is accounted for by the electron-
withdrawing inductive effect of the adjacent -NH3+
group.
NH3+
RCHCOOH H2O
NH3+
RCHCOO- H3O++ pKa = 2.19+
Note that the NH2 will be protonated at these low pHs
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Acidity: side chain -COOHAcidity: 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 (ppKKaa 2.35 2.35)
-COOH group of aspartic acid (ppKKaa 3.86 3.86)
-COOH group of glutamic acid (ppKKaa 4.07 4.07)
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Acidity: Acidity: -NH-NH33++ groups groups
The average value of pKa for an -NH3+ group is
9.47, compared with a value of 10.76 for a 1° alkylammonium ion.
NH3+
RCHCOO-
H2O
NH3+
CH3CHCH3 H2O
NH2
RCHCOO-
NH2
CH3CHCH3
H3O+
H3O+ pKa = 10.60++
+ pKa = 9.47+
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Details: The Guanidine Group of ArgDetails: The Guanidine Group of Arg
• The basicity of the guanidine group is attributed to the large resonance stabilization of the protonated form relative to the neutral form.
CRNH
NH2+
NH2
C
NH2+
NH2
RNH
CRN
NH2
NH2
NH2
CRNH
NH2
H3O+
H2O
+
:
: :
:
::
::
+
pKa = 12.48
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Details: Imidazole GroupDetails: Imidazole Group
• The imidazole group is a heterocyclic aromatic amine.
N
NH
H
COO-
NH3+ N
N
H
H
COO-
NH3+
H2O
H3O+
H
COO-
NH3+N
NH3O+
Not a part of the aromatic sextet;the proton acceptor pKa 6.10+
+
•• +
••
••
••
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Useful Recall from buffer solutionsUseful Recall from buffer solutions
Ka = [H+] [A-]/[HA]
If Ka = [H+] then [A-] = [HA]
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Isoelectric Point Isoelectric Point
Isoelectric point (pI):Isoelectric point (pI): pH at which an amino acid, polypeptide, or protein has a total charge of zero.• The pI for glycine, for example, falls between the pKa
values for the carboxyl and amino groups.
pI = 12 (pKa COOH + pKa NH3
+)
= 21 (2.35 + 9.78) = 6.06
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Isoelectric Point of glycine continued Isoelectric Point of glycine continued
pKa = pH-log([conj base]/[acid])
At pH = 6.06
For carboxyl group 2.35 = 6.06 - log ([RCO2-]/[RCO2H])
6.06- 2.35 = 3.71 = log ([RCO2-]/[RCO2H])
([RCO2-]/[RCO2H]) = 103.71 or 99.98% ionized as neg ion.
For amino group 9.78 = 6.06 - log([RNH2]/[RNH3+])
([RNH2]/[RNH3+]) = 10-3.72 or 99.98% protonated.
On average Zero Chg.
pI = 12 (pKa COOH + pKa NH3
+)
= 21 (2.35 + 9.78) = 6.06
Again
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Furthermore…..Furthermore…..
+H3N CH C
H
OH
O
+H3N CH C
H
O-
O
H2N CH C
H
O-
O
pH increases
pKa2.35 9.78
pI
[A+] = [C-]
A+ B C-
27-27-1919
Titration of conjugate acid of glycine with NaOHTitration of conjugate acid of glycine with NaOH..
Buffer solution. [-CO2H] = [-CO2
-]
Strongly acid -CO2H and -NH3
+
Isoelectric. Zero net charge.
Buffer solution. [-NH3
+]=[-NH2]
Strongly basic-CO2
- and NH2
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Isoelectric PointIsoelectric Point
6.115.415.656.066.046.045.745.916.305.685.605.886.00
pKa ofpKa ofpKa of
pI
----------------
----------------------------
--------
valine 2.29 9.72tryptophan 2.38 9.39
9.102.09threonineserine 2.21 9.15
10.602.00prolinephenylalanine 2.58 9.24
9.212.28methionine9.742.33leucine
isoleucine 2.32 9.76glycine 2.35 9.78
9.132.17glutamine8.802.02asparagine9.872.35alanine
Side Chain
Nonpolar &polar side chains NH3
+ COOH
If pH is lower than pI then more protonated molecules. If higher then more negative charge.
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Isoelectric PointIsoelectric Point
10.76
2.98
5.023.08
7.649.74
5.63
pKa ofpKa ofpKa ofpI
10.079.112.20tyrosine
lysine 2.18 8.95 10.536.109.181.77histidine
glutamic acid 2.10 9.47 4.078.0010.252.05cysteine
aspartic acid 2.10 9.82 3.86
arginine 2.01 9.04 12.48
Side Chain
AcidicSide Chains NH3
+ COOH
pKa ofpKa ofpKa of
pISide Chain
BasicSide Chains NH3
+ COOH
Three buffered pHs
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Aspartic acidAspartic acid
NH3+
CH
C
H2C
OH
O
CHO
O
NH3+
CH
C
H2C
O-
O
CHO
O
NH3+
CH
C
H2C
O-
O
C-O
O
NH2
CH
C
H2C
O-
O
C-O
O
pKa 2.10 3.86 9.82
A+ B C- D2-
pI = (2.10 + 3.86)/2[A+] = [C-][D2-] approx 0
[A+] = [B]pH = pKa
[B] = [C-]
Note species B has zero net charge. pKa1 and pKa2 control [A+] and [C-] which should be equal.
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ArginineArginine
+H3N CH C
CH2
OH
O
CH2
CH2
NH
C
NH2
NH2+
+H3N CH C
CH2
O-
O
CH2
CH2
NH
C
NH2
NH2+
H2N CH C
CH2
O-
O
CH2
CH2
NH
C
NH2
NH2+
2.01 9.04 12.48pKa
H2N CH C
CH2
O-
O
CH2
CH2
NH
C
NH2
NH
B+A2+ C D-
pI = (9.04+12.48)/2 =10.76[B+] = [D-]; [A2+] about 0
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ElectrophoresisElectrophoresis
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, polyacrylamide and agarose gels, and cellulose acetate as solid supports.
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ElectrophoresisElectrophoresis
• 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 isoelectric point remain at the origin.• After separation is complete, the strip is dried and
developed to make the separated amino acids visible.• After derivitization with ninhydrin, 19 of the 20 amino
acids give the same purple-colored anion; proline gives an orange-colored compound.
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ElectrophoresisElectrophoresis
• The reagent commonly used to detect amino acid is ninhydrin.
RCHCO-
O OHO
OOH
NH3+
O
O-
N
O
O
O
RCH CO2 H3O++
An -amino acid
Purple-colored anion
+ +
2+
Ninhydrin
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Polypeptides & ProteinsPolypeptides & 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:Peptide bond: The special name given to the amide bond between the -carboxyl group of one amino acid and the -amino group of another.
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Serinylalanine (Ser-Ala)Serinylalanine (Ser-Ala)
H2N HO
O
HHOCH2
Serine(Ser, S)
H2NO
OH
H CH3
Alanine(Ala, A)
+
H2NN
OH
HOCH2
H
H
CH3O
H O
Serinylalanine(Ser-Ala, (S-A)
peptide bond
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PeptidesPeptides
• Peptide: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:Dipeptide: A molecule containing two amino acids joined by a peptide bond.
• TripeptideTripeptide: A molecule containing three amino acids joined by peptide bonds.
• PolypeptidePolypeptide: A macromolecule containing many amino acids joined by peptide bonds.
• ProteinProtein: A biological macromolecule of molecular weight 5000 g/mol or greater, consisting of one or more polypeptide chains.
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Writing PeptidesWriting 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.
H3N
OH
NH O
HN
COO-
O-
OC6H5O
+
C-terminalamino acid
N-terminalamino acid
Ser-Phe-Asn
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Writing PeptidesWriting Peptides
• The tetrapeptide Cys-Arg-Met-As• At pH 6.0, its net charge is +1.
HN
NH O
HN
O-
OO
O
NH2
SCH3
NH
NH2+H2N
OH3N
SH C-terminalamino acid
N-terminalamino acid
pKa 12.48
pKa 8.00
+
At pH 8 it would be half ionized.
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Primary StructurePrimary Structure
Primary structure:Primary structure: The sequence of amino acids in a polypeptide chain; read from the N-terminal 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 ion-
exchange chromatography.
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Ion Exchange ChromatographyIon Exchange Chromatography
Analysis of a mixture of amino acids by ion exchange chromatography
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Cyanogen BromideCyanogen Bromide, BrCN, BrCN
• BrCN Selectively cleaves of peptide bonds formed by the carboxyl group of methionine.
PN-C-NH CH C NH-PC
O O
CH2
CH2-S-CH3
cyanogen bromide isspecific for the cleavageof this peptide bond
from theN-terminalend
from theC-terminal end
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Cyanogen Bromide, BrCNCyanogen Bromide, BrCN
O
S-CH3
HNC-NH
OpeptideCOO-
H3N peptideBr C N
H2O
O
OC-NH
O
H3N peptide
H3N peptide COO- CH3S-C N
side chainof methionine
+0.1 M HCl
A substituted -lactone ofthe amino acid homoserine
Methylthiocyanate
Mechanism to follow
27-27-3636
Cyanogen Bromide, BrCNCyanogen Bromide, BrCN
• Step 1: Nucleophilic displacement of bromine.
O
S-CH3
H3N C-NH
O HN COO-
Br C N
O
S-CH3
C N
H3N C-NH
O HN COO-
Br
Cyanogen bromide
a sulfonium ion; a good leaving group
: ::
27-27-3737
Cyanogen Bromide, BrCNCyanogen Bromide, BrCN
• Step 2: Internal nucleophilic displacement of methyl thiocyanate.
O
S-CH3
C N
HN COO-
H3N C-NH
O
O
H3N C-NH
OHN COO-
CH3-S-C N
An iminolactonehydrobromide
+
Methylthiocyanate
:
:
::
27-27-3838
Cyanogen Bromide, BrCNCyanogen Bromide, BrCN
• Step 3: Hydrolysis of the imino group.
O
H3N C-NH
OHN COO-
H2O
OH3N C-NH
O
O H3N COO-
A substituted -lactone ofthe amino acid homoserine
27-27-3939
Enzyme CatalysisEnzyme Catalysis
A group of protein-cleaving enzymes called proteases can be used to catalyze the hydrolysis of specific peptide bonds.
Phenylalanine, tyrosine, tryptophanChymotrypsin
Arginine, lysineTrypsin
Catalyzes Hydrolysis of Peptide Bond Formed by Carboxyl Group ofEnzyme
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Edman DegradationEdman Degradation
Edman degradation:Edman degradation: Cleaves the N-terminal amino acid of a polypeptide chain.
S=C=N-Ph
H2N COO-HN
NO
R
SPh
H3NNH
R
O
COO- +
+
N-terminalamino acid
A phenylthiohydantoin
Phenyl isothiocyanate
+
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Edman DegradationEdman Degradation
• Step 1: Nucleophilic addition to the C=N group of phenylisothiocyanate and proton tautomerization
H2NNH
R
O
COO-
Ph N C S
HN
S
RO
NH COO-
Ph NH
A derivative of N-phenylthiourea
:: :
27-27-4242
Edman DegradationEdman Degradation
• Step 2: Nucleophilic addition of sulfur to the C=O of the adjacent amide group and acid catalysis.
HN
S
RO
NH COOHPh N
H
H
HN
S
R
O
Ph-N
HN
S
R
Ph-N
O–H
NH
H
COOH
H+
H3N COOH
H+
+
A thiazolinone
+
+
+
27-27-4343
Edman DegradationEdman Degradation
• Step 3: Isomerization of the thiazolinone ring.
HN
S
R
O
Ph-N
+ H-Nu
R
HN
N SH Nu
O
Ph
R
HN
S NH
Ph
Nu
O - H-NuHN
N
R
O
SPh
A thiazolinone
A phenylthiohydantoin
keto-enoltautomerism
substitution
27-27-4444
DNFB tagging of N terminal AADNFB tagging of N terminal AA
F
NO2
NO2
H2N
R
O
DNFB
HN
R
NO2
O2N O
hydrolysisHN
R
OH
NO2
O2N O
plus unlabeled AA
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Carboxypeptidase cleavage of C terminal AACarboxypeptidase cleavage of C terminal AA
Treatment of peptide with carboxypeptidase cleaves the peptide linkage adjacent to the free alpha carboxyl group. It may then be identified.
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Primary Structure, examplePrimary Structure, example
Deduce the 1° structure of this pentapeptide
pentapeptideEdman Degradation
Hydrolysis - Chymotrypsin
Fragment AFragment B
Hydrolysis - TrypsinFragment CFragment D
Arg, Glu, His, Phe, SerGlu
Glu, His, PheArg, Ser
Arg, Glu, His, Phe
Ser
Experimental ProcedureAmino Acid Composition
Phenylalanine, tyrosine, tryptophanChymotrypsin
Arginine, lysineTrypsin
Catalyzes Hydrolysis of Peptide Bond Formed by Carboxyl Group ofEnzyme
using
Glu-
Glu-His-Phe
Glu-His-Phe-Arg-Ser
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Polypeptide SynthesisPolypeptide Synthesis
The problem in protein synthesis is how to join the -carboxyl group of aa-1 by an amide bond to the -amino group of aa-2, and not vice versa.
aa1
H3NCHCO-
O
aa2
H3NCHCO-
O
aa1 aa2
H3NCHCNHCHCO-
OOH2O
? +++
++
27-27-4848
Polypeptide Synthesis StrategyPolypeptide Synthesis Strategy
• Protect the -amino group of aa-1.• Activate the -carboxyl group of aa-1.• Protect the -carboxyl group of aa-2.
+
+
form peptide bond
protectinggroup
activatinggroup
protectinggroup
O O
aa2aa1
Z-NHCHC-Y H2NCHC-X
Z-NHCHCNHCHC-X H-Y
O Oaa1 aa2
27-27-4949
Amino-ProtectionAmino-Protection
• convert them to amides.
O
(CH3)3COCOCOC(CH3)3
O O
(CH3)3COC-
O
PhCH2OC-
O
PhCH2OCCl
Di-tert-butyl dicarbonate
Benzyloxycarbonylchloride
tert-Butoxycarbonyl (BOC-) group
Benzyloxycarbonyl(Z-) group
27-27-5050
Amino-ProtectionAmino-Protection
• Treatment of an amino group with either of these reagents gives a carbamate (an ester of the monoamide of carbonic acid).
• A carbamate is stable to dilute base but can be removed by treatment with HBr in acetic acid.
PhCH2OCNH-peptide
OHBr
CH3COOHPhCH2Br CO2 H3N-peptide
A Z-protectedpeptide
+ ++
Benzylbromide
Unprotectedpeptide
PhCH2OCClO
CH3
H3NCHCO-
O 1. NaOH
2. HCl, H2OCH3
PhCH2OCNHCHCOHO O
Alanine N-Benzyloxycarbonylalanine(Z-Ala)
++
Benzyloxycarbonylchloride (Z-Cl)
27-27-5151
Amino-Protecting GroupsAmino-Protecting Groups
The benzyloxycarbonyl group is also removed by hydrogenolysis.• The intermediate carbamic acid loses carbon dioxide
to give the unprotected amino group.
PhCH2OCNH-peptide
OH2
PdPhCH3 CO2 H2N-peptide
A Z-protectedpeptide
Unprotectedpeptide
Toluene+++
27-27-5252
Carboxyl-Protecting Groups. EstersCarboxyl-Protecting Groups. Esters
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; they are also removed by treatment with HBr in acetic acid
27-27-5353
Peptide Bond FormationPeptide 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.
1,3-Dicyclohexylcarbodiimide (DCC)
+
N,N' -dicyclohexylurea (DCU)
C NN
H
N NC
H
O
H2O
In bringing about formation of a peptide bond, DCC acts a dehydrating agent.
27-27-5454
Peptide Bond FormationPeptide Bond Formation
Carboxyl-protectedaa2
Amino-protectedaa1
++CHCl3
Z-NHCHC-OH H2 NCHCOCH3
Amino and carboxyl protected dipeptide
+Z-NHCHC-NHCHCOCH3
DCC
DCU
R1 R2
R1 R2
O O
O O
27-27-5555
Solid-Phase SynthesisSolid-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.
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Solid-Phase SynthesisSolid-Phase Synthesis
The solid support used in the Merrifield solid phase synthesis.
27-27-5757
27-27-5858
Solid-Phase SynthesisSolid-Phase Synthesis
• Merrifield synthesized the enzyme ribonuclease, a protein containing 124 amino acids
27-27-5959
Peptide Bond GeometryPeptide 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.
• Model of the zwitterion form of Gly-Gly viewed from two perspectives to show the planarity of the six atoms of the peptide bond and the preferred s-trans geometry.
27-27-6060
Peptide Bond GeometryPeptide 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.
C
C
N
H
C
C
COO
C N
H
+
-: :
:
: : :
27-27-6161
Peptide Bond GeometryPeptide 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
C
O
C N
H
• • ••
••
CC
O
C N
H• • ••
••
s-trans s-cis
27-27-6262
Secondary StructureSecondary Structure
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.
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Secondary StructureSecondary Structure
• Hydrogen bonding between amide groups.
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Secondary StructureSecondary 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-Helix:: A type of secondary structure in which a
section of polypeptide chain coils into a spiral, most commonly a right-handed spiral.
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The The -Helix-Helix
• The polypeptide chain is repeating units of L-alanine.
H bonds (C=O…H) parallel to axis of helix
27-27-6666
The The -Helix-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.
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The The -Helix-Helix
An -helix of repeating units of L-alanine • A ball-and-stick model
viewed looking down the axis of the helix.
• A space-filling model viewed from the side.
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-Pleated Sheet-Pleated Sheet
The antiparallel -pleated sheet consists of adjacent polypeptide chains running in opposite directions:• 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.
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-Pleated Sheet-Pleated Sheet
• -pleated sheet with three polypeptide chains running in opposite directions (antiparallel).
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Tertiary StructureTertiary Structure
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.
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Tertiary StructureTertiary Structure
• A ribbon model of myoglobin.
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Quaternary StructureQuaternary Structure
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:Hydrophobic effect: The tendency of nonpolar groups to cluster together in such a way as to be shielded from contact with an aqueous environment.
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Quaternary StructureQuaternary Structure
• The quaternary structure of hemoglobin. The -chains in yellow, the heme ligands in red, and the Fe atoms as white spheres.
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Quaternary StructureQuaternary 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.
ProteinNumber ofSubunits
Insulin
Hemoglobin
Alcohol dehydrogenase
Lactate dehydrogenase
Aldolase
Glutamine synthetaseTobacco mosaic virus protein disc
6
4
2
4
4
1217