27 27-1 Organic Chemistry William H. Brown & Christopher S. Foote.

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Organic Organic Chemistry Chemistry

William H. Brown &William H. Brown &

Christopher S. FooteChristopher S. Foote

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27-2

Amino AcidsAmino Acids

& Proteins& Proteins

Chapter 27Chapter 27

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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

O

RCHCO-

NH3+

O

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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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Nonpolar side chainsNonpolar 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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Polar side chainsPolar 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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Acidic & basic side chainsAcidic & 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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Other Amino AcidsOther Amino Acids

NH3+

COO-

NH

H2N

O

NH3+

COO-

H3N

HO O CH2CHCOO-

NH3+

I I

I I

NH3+

-O

O

L-CitrullineL-Ornithine

L-Thyroxine, T4 4-Aminobutanoic acid

(γ- , )Aminobutyric acid GABA

+

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Acid-Acid-

BaseBase

Proper-Proper-

tiesties

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

+α−COOH

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Acid-Base PropertiesAcid-Base PropertiespKa 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

+α−COOH

pKa ofpKa ofpKa of Side Chain

BasicSide Chains α−NH3

+α−COOH

carboxylcarboxylsufhydrylphenolic

guanidinoimidazole1° amino

SideChainGroup

SideChainGroup

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Acidity: Acidity: -CO-CO22H Groups H 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+ pKa = 2.19

NH3+NH3

+RCHCOO-RCHCOOH H3O+H2O+

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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 (pKpKaa 2.35 2.35)

-COOH group of aspartic acid (pKpKaa 3.86 3.86)

γ-COOH group of glutamic acid (pKpKaa 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

+ pKa = 9.47

NH3+

NH2

RCHCOO- RCHCOO-+ H2O H3O+

pKa = 10.60

NH3+ NH2

CH3CHCH3 CH3CHCH3 + H3O++ H2O

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Basicity-Guanidine GroupBasicity-Guanidine Group• basicity of the guanidine group is attributed to the

large resonance stabilization of the protonated form relative to the neutral form

+

pKa = 12.48

C

NH2+

CRNH

NH2+

NH2

NH2

RNH CRNH

NH2

NH2

CRN

NH2

NH2

+ H3O+

H2O

:

: :

:

:

:

:

:

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Basicity- Imidazole GroupBasicity- Imidazole Group• the imidazole group is a heterocyclic aromatic amine

N

NH

H

COO-

NH3+ N

N

H

H

COO-

NH3+

H2O

H3O+

N

NH

COO-

NH3+

H3O+

Not a part of the aromatic sextet;the proton acceptor pKa 6.10+

+

•• +

••

••

••

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Ionization vs pHIonization 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 H2O

[H3O+]

α−COO-

[H3O+]

H3O+

pKa = 2.00+ +

[α-COOH

[α-COO-]Ka = =

Ka

[α-COOH

[α-COO-]or

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Ionization vs pHIonization vs pH• substituting the value of pKa (2.00) for the hydrogen

ion concentration at pH 7.0 (1.0 x 10-7) gives

• 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

[H3O+]=

Ka

[-COOH

[-COO-]= 1.00 x 105

1.00 x 10-7

1.00 x 10-2

=

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Ionization vs pHIonization 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+

H2O

[H3O+]

α−NH2 H3O++pKa = 10.00

+

[α-NH2]

[α-NH3+]

Ka=

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Ionization vs pHIonization vs pH• substituting values for pKa of an -NH3

+ group and the hydrogen ion concentration at pH 7.0 gives

• thus at pH 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

[H3O+]

[-NH2 ]

[ -NH3+]

Ka= =1.00 x 10-10

1.00 x 10-7= 1.00 x 10-3

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Henderson-HasselbalchHenderson-Hasselbalch• for the ionization of any weak acid HA

• taking the log and rearranging gives

• substitution pH and pKa gives the Henderson-Hasselbalch equation

+ H3O++ H2O Ka = A-HA[HA]

[A-][H3O+]

+-log Ka -log [H3O+] = log

[A-]

[HA]

[A-]

[HA]log=pH pKa +

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Henderson-HasselbalchHenderson-Hasselbalch• using the Henderson-Hasselbalch equation

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

[A-]

[HA]log=pH pKa +

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Isoelectric Point Isoelectric Point Isoelectric point, pI, of an amino acid: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

pI = 12 (pKa −COOH + pKa −NH3

+)

= 21 (2.35 + 9.78) = 6.06

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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

+α−COOH

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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

+α−COOH

pKa ofpKa ofpKa of

pISide Chain

BasicSide Chains α−NH3

+α−COOH

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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, 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

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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 their isoelectric point remain at the origin

• after separation is complete, the strip is dried and developed to make the separated amino acids visible

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ElectrophoresisElectrophoresis• a reagent commonly used to detect amino acid is

ninhydrin

An - amino acid

- Purple colored anion

+ +

2+

Ninhydrin

OHO

OOH

O

NH3+

ON

O

O O

O-

RCHCO-

RCH CO2 + H3O+

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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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Serylalanine (Ser-Ala)Serylalanine (Ser-Ala)

H2N HO

O

HHOCH2

H2NO

OH

H CH3

H2NN

OH

HOCH2

H

H

CH3O

H O

Serine(Ser, S)

Alanine(Ala, A)

+

Serylalanine(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 of 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-Asp

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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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Cyanogen Bromide, BrCNCyanogen Bromide, BrCN• cleavage of peptide bonds formed by the carboxyl

group of methionine

PN-C-NH CH C

CH2

O

NH-PC

O

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 γ- lactone of the amino acid homoserine

Methylthiocyanate

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Cyanogen Bromide, BrCNCyanogen Bromide, BrCN• Step 1: nucleophilic displacement of bromine

Br C N

Br -

Cyanogen bromide

a sulfonium ion; a good leaving group

O

S-CH3

O

S-CH3

C N

HN COO-

H3N C-NHHN COO-

H3N C-NH

OO

: ::

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Cyanogen Bromide, BrCNCyanogen Bromide, BrCN• Step 2: internal nucleophilic displacement

O

S-CH3

C N

HN COO-

H3N C-NH

O

O

H3N C-NH

OHN COO-

CH3-S-C N

An iminolactonehydrobromide

+

Methylthiocyanate

:

:

::

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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 γ- lactone of the amino acid homoserine

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Enzyme CatalysisEnzyme Catalysis A group of protein-cleaving enzymes 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

HN

NO

R

SPh

H3NNH

R

O

COO-+

H2N COO-+

N-terminalamino acid

A phenylthiohydantoin

Phenyl isothiocyanateS=C=N-Ph

+

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Edman DegradationEdman Degradation• Step 1: nucleophilic addition to the C=N group of

phenylisothiocyanate

H2NNH

R

O

COO-

Ph N C S

HN

S

RO

NH COO-

Ph NH

A derivative of N-phenylthiourea

:

: :

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Edman DegradationEdman Degradation• Step 2: nucleophilic addition of sulfur to the C=O of

the adjacent amide group

HN

S

RO

NH COOHPh N

H

H

HN

S

R

Ph-N

O–H

NH

H

COOH

H+

HN

S

R

O

Ph-N

H+

H3N COOH+

A thiazolinone

+

+

+

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Edman DegradationEdman Degradation• Step 3: isomerization of the thiazolinone ring

HN

S

R

O

Ph-N

+ H-Nu

R

HN

S NH

Ph

Nu

O - H-Nu

HN

N

R

O

SPh

A thiazolinone

A phenylthiohydantoin

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Primary StructurePrimary StructureExample 27.8Example 27.8 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

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Polypeptide SynthesisPolypeptide Synthesis The problem is join the -carboxyl group of aa-

1 by an amide bond to the -amino group of aa-2, and not vice versa

? +++

++

aa1 aa2 aa1 aa2

H3 NCHCO-

H3 NCHCO-

H3 NCHCNHCHCO-

H2 OO O O O

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Polypeptide SynthesisPolypeptide Synthesis• 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

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Amino-Protecting GroupsAmino-Protecting Groups• the most common strategy for protecting amino

groups and reducing their nucleophilicity is to 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

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Amino-Protecting GroupsAmino-Protecting Groups• treatment of an amino group with either of these

reagents gives a carbamate (an ester of the monoamide of carbonic acid)

Alanine

N-Benzyloxycarbonylalanine(Z-ala)

++

Benzyloxycarbonyl chloride (Z-Cl)

PhCH2OCCl1. NaOH

2. HCl, H2 O H3 NCHCO

-

PhCH2OCNHCHCOH

CH3

CH3

O

O O

O

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Amino-Protecting GroupsAmino-Protecting Groups• a carbamate is stable to dilute base but can be

removed by treatment with HBr in acetic acid

A Z-protected peptide

+ ++

Benzylbromide

Unprotectedpeptide

PhCH2OCNH-peptide HBrCH3COOH

PhCH2Br CO2 H3 N-peptide

O

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Amino-Protecting GroupsAmino-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

Unprotectedpeptide

Toluene++

+

A Z-protected peptide

PhCH2OCNH-peptide H2

PhCH3 CO2 H2 N-peptide

PdO

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Carboxyl-Protecting GrpsCarboxyl-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

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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

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Peptide Bond FormationPeptide Bond Formation• DCC acts as dehydrating in bringing about formation

of a peptide bond

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

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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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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

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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

+

-: :

:: : :

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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

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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

hydrogenbonding

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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 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

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27-62

-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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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

NH O

HN

SH

a disulfidebondreduction

oxidationside chainsof cysteine

HN

O

NH

SH

NH O

HN

S

HN

O

NH

S

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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• 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

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Prob 27.19Prob 27.19From what amino acid is histamine derived? By what type of reaction is the precursor amino acid converted to histamine?

N

N

H

CH2CH2NH2

Histamine

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Prob 27.21Prob 27.21From which protein-derived amino acid are norepinephrine and epinephrine synthesized? What types of reactions are involved in each biosynthesis?

(b)(a)

Norepinephrine Epinephrine(Adrenaline)

HO

HO

NH2

H OHHO

HO

CH3

HN

H OH

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Prob 27.22Prob 27.22From which amino acid are serotonin and melatonin derived? What types of reactions are involved in the biosynthesis of each?

Melatonin

N

HO CH2CH2NH2

HSerotonin

CH2CH2NHCCH3

N

CH3O

H

(a)

(b)O

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Prob 27.39Prob 27.39Do you expect the modified guanidino group of cimetidine to be more basic or less basic that the guanidino group of arginine?

CH2SCH2CH2NHCNHCH3H3C

NHNCimetidine(Tagamet)

N-CN

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Prob 27.40Prob 27.40Draw a structural formula for the product formed by treating alanine with each reagent.

(a) (b)CCl, (CH3CH2)3N

O

O

OH

OH

O

(c)

(d)

CH2OCCl, NaOH

(CH3 )3COCOCOC(CH3)3, NaOH

O O

O

(f)

(e)Product (c) + L-Alanine ethyl ester + DCC

Product (d) + L-Alanine ethyl ester + DCC

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Prob 27.45Prob 27.45A 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

His-Leu-Cys-Gly-Ser

Gly-Ser-His-Leu-Val

Gln-His-Leu-Cys

His-Leu-Val-Glu

Leu-Val-Glu-Ala

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Prob 27.48Prob 27.48Name the amino acids in glutathione. What is unusual about the peptide bond formed by the N-terminal amino acid?

+

Glutathione

O

H3N NH O

HN

O-

OOSH

O-

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Prob 27.49Prob 27.49Name the amino acids in aspartame. Estimate the isoelectric point of this dipeptide.

+H3N

O

HN

O

O

Aspartame

O

-OCH3

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Prob 27.51Prob 27.51Write 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.

(N-Terminal end ofa polypeptide chain)

+

2,4-Dinitro-fluorobenzene

NO2

FO2N

R2R1

H2 NCHCNHCHC-polypeptide

O Oderivatizedpolypeptide

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Amino Acids Amino Acids

& Proteins& ProteinsEnd of Chapter 27End of Chapter 27