Organic Chemistry

Paula Yurkanis Bruice

Chapter 23

Amino Acids, Peptides, and Protein - all with Video Answers

Educators

Chapter Questions

Problem 1

a. Explain why, when the imidazole ring of histidine is protonated, the double-bonded nitrogen is the nitrogen that accepts the proton.
b. Explain why, when the guanidino group of arginine is protonated, the double-bonded nitrogen is the nitrogen that accepts the proton.

Zubair Abdulla

Zubair Abdulla

Numerade Educator

Problem 2

a. Which isomer- $(R)$ -alanine or $(S)$ -alanine- is D-alanine?
b. Which isomer- $(R)$ -aspartate or ( $S$ )-aspartate - is D-aspartate?
c. Can a general statement be made relating $R$ and $S$ to $\mathrm{D}$ and $\mathrm{L} ?$

Megha Ramappan

Numerade Educator

Problem 3

Which amino acids in Table 23.1 have more than one asymmetric carbon?

Tyler Walter

Numerade Educator

Problem 4

Why are the carboxylic acid groups of the amino acids so much more acidic ( $\mathrm{p} K_{\mathrm{a}} \sim 2$ ) than a carboxylic acid such as acetic acid $\left(\mathrm{p} K_{\mathrm{a}}=4.76\right) ?$

Megha Ramappan

Numerade Educator

Problem 5

Draw the form in which each of the following amino acids predominantly exists at physiological pH (7.3):
a. aspartic acid
b. histidine
c. glutamine
d. lysine
e. arginine
f. tyrosine
Both carboxyl groups are in their basic forms because the $\mathrm{pH}$ is greater than their $\mathrm{p} K_{\mathrm{a}}$ 's. The protonated amino group is in its acidic form because the $\mathrm{pH}$ is less than its $\mathrm{p} K_{\mathrm{a}}$

Megha Ramappan

Numerade Educator

Problem 6

Draw the form in which glutamic acid predominantly exists in a solution with the following pH:
a. $\mathrm{pH}=0$
b. $\mathrm{pH}=3$
c. $\mathrm{pH}=6$
d. $\mathrm{pH}=11$

Tyler Walter

Numerade Educator

Problem 7

a. Why is the $\mathrm{p} K_{\mathrm{a}}$ of the glutamic acid side chain greater than the $\mathrm{p} K_{\mathrm{a}}$ of the aspartic acid side chain?
b. Why is the $\mathrm{p} K_{\mathrm{a}}$ of the arginine side chain greater than the $\mathrm{p} K_{\mathrm{a}}$ of the lysine side chain?

Megha Ramappan

Numerade Educator

Problem 8

Explain why the pI of lysine is the average of the $\mathrm{p} K_{\mathrm{a}}$ values of its two protonated amino groups.

Tyler Walter

Numerade Educator

Problem 9

Calculate the pI of each of the following amino acids:
a. asparagine
b. arginine
c. serine

Tyler Walter

Numerade Educator

Problem 10

a. Which amino acid has the lowest pI value?
b. Which amino acid has the highest pI value?
c. Which amino acid has the greatest amount of negative charge at $\mathrm{pH}=6.20 ?$
d. Which amino acid-glycine or methionine-has a greater negative charge at $\mathrm{pH}=6.20 ?$

Megha Ramappan

Numerade Educator

Problem 11

Explain why the pI values of tyrosine and cysteine cannot be determined by the method just described.

Tyler Walter

Numerade Educator

Problem 12

A mixture of seven amino acids (glycine, glutamate, leucine, lysine, alanine, isoleucine, and aspartate) is separated by TLC. Explain why only six spots show up when the chromatographic plate is sprayed with ninhydrin and heated.

Megha Ramappan

Numerade Educator

Problem 13

Why are buffer solutions of increasingly higher pH used to elute the column that generates the chromatogram shown in Figure $23.5 ?$

Tyler Walter

Numerade Educator

Problem 14

Explain the order of elution (with a buffer of $\mathrm{pH}$ 4) of each of the following pairs of amino acids on a column packed with Dowex ® 50 (Figure 23.3):
a. aspartate before serine
b. glycine before alanine
c. valine before leucine
d. tyrosine before phenylalanine

Tyler Walter

Numerade Educator

Problem 15

In what order would the following amino acids be eluted with a buffer of $\mathrm{pH} 4$ from a column containing an anion-exchange resin?
histidine, serine, aspartate, valine

Megha Ramappan

Numerade Educator

Problem 16

Why is excess ammonia used in the preceding reaction?

Megha Ramappan

Numerade Educator

Problem 17

Pig liver esterase is an enzyme that catalyzes the hydrolysis of esters. It hydrolyzes esters of L-amino acids more rapidly than esters of D-amino acids. How can this enzyme be used to separate a racemic mixture of amino acids?

Ronald Prasad

Numerade Educator

Problem 18

Amino acids can be synthesized by reductive amination of $\alpha$ -keto acids (Section 21.8 ).
Biological organisms can also convert $\alpha$ -keto acids into amino acids, but because $\mathrm{H}_{2}$ and metal catalysts are not available to the cell, they do so by a different mechanism (Section 25.6.)
a. What amino acid is obtained from the reductive amination of each of the following metabolic intermediates in the cell?
b. What amino acids are obtained from the same metabolic intermediates when they are synthesized in the laboratory?

Megha Ramappan

Numerade Educator

Problem 19

Draw a peptide bond in a cis configuration.

Tyler Walter

Numerade Educator

Problem 20

a. How many different octapeptides can be made from the 20 naturally occurring amino acids?
b. How many different proteins containing 100 amino acids can be made from the 20 naturally occurring amino acids?

Zubair Abdulla

Numerade Educator

Problem 21

Which bonds in the backbone of a peptide can rotate freely?

Zubair Abdulla

Numerade Educator

Problem 22

What is unusual about glutathione's structure? (If you can't answer this question, draw the structure you would expect for a tripeptide of glutamate, cysteine, and glycine, and compare your structure with the structure of glutathione.)

Anupa Sharad Medhekar

Anupa Sharad Medhekar

Numerade Educator

Problem 23

What dipeptides would be formed by heating a mixture of valine and N-protected leucine?

Zubair Abdulla

Numerade Educator

Problem 24

Suppose you are trying to synthesize the dipeptide Val-Ser. Compare the product that would be obtained if the carboxyl group of $\mathrm{N}$ -protected valine were activated with thionyl chloride with the product that would be obtained if the carboxyl group were activated with DCC.

Zubair Abdulla

Numerade Educator

Problem 25

Show the steps in the synthesis of the tetrapeptide Leu-Phe-Lys-Val.

Zubair Abdulla

Numerade Educator

Problem 26

a. Calculate the overall yield of bradykinin if the yield for the addition of each amino acid to the chain is $70 \%$
b. What would be the overall yield of a peptide containing 15 amino acid residues if the yield for the incorporation of each is $80 \% ?$

Zubair Abdulla

Numerade Educator

Problem 27

Show the steps in the synthesis of the peptide in Problem $25,$ using Merrifield's method.

Nima Gharibi

Numerade Educator

Problem 28

Write the mechanism for the reaction of a cysteine residue with iodoacetic acid.

Zubair Abdulla

Numerade Educator

Problem 29

A decapeptide undergoes partial hydrolysis to give peptides whose amino acid compositions are shown. Reaction of the intact decapeptide with Edman's reagent releases PTH-Gly. What is the sequence of the decapeptide?
a. Ala, Trp
b. Val, Pro, Asp
c. Pro, Val
d. Ala, Glu
e. Trp, Ala, Arg
f. Arg, Gly
g. Glu, Ala, Leu
h. Met, Pro, Leu, Glu

Zubair Abdulla

Numerade Educator

Problem 30

Why won't cyanogen bromide cleave at cysteine residues?

Tyler Walter

Numerade Educator

Problem 31

In determining the primary structure of insulin, what would lead you to conclude that it had more than one polypeptide chain?

Zubair Abdulla

Numerade Educator

Problem 32

Determine the amino acid sequence of a polypeptide from the following results:
Acid hydrolysis gives Ala, Arg, His, 2 Lys, Leu, 2 Met, Pro, 2 Ser, Thr, Val.
Carboxypeptidase A releases Val.
Edman's reagent releases PTH-Leu.
Cleavage with cyanogen bromide gives three peptides with the following amino acid compositions:
1. His, Lys, Met, Pro, Ser
2. Thr, Val
3. Ala, Arg, Leu, Lys, Met, Ser
Trypsin-catalyzed hydrolysis gives three peptides and a single amino acid:
1. Arg, Leu, Ser
2. Met, Pro, Ser, Thr, Val
3. Lys
4. Ala, His, Lys, Met

Zubair Abdulla

Numerade Educator

Problem 33

Determine the primary structure of an octapeptide from the following data:
Acid hydrolysis gives 2 Arg, Leu, Lys, Met, Phe, Ser, Tyr.
Carboxypeptidase A releases Ser.
Edman's reagent releases Leu.
Cyanogen bromide forms two peptides with the following amino acid compositions:
1. Arg, Phe, Ser
2. Arg, Leu, Lys, Met, Tyr
Trypsin forms the following two peptides and two amino acids:
1. Arg
2. Ser
3. Arg, Met, Phe
4. Leu, Lys, Tyr

Zubair Abdulla

Numerade Educator

Problem 34

How long is an $\alpha$ -helix that contains 74 amino acids? Compare the length of this $\alpha$ -helix with the length of a fully extended peptide chain containing the same number of amino acids. (The distance between consecutive amino acids in a fully extended chain is $3.5 \AA .$ )

Zubair Abdulla

Numerade Educator

Problem 35

How would a protein that resides in the interior of a membrane fold, compared with the water-soluble protein just discussed?

Tyler Walter

Numerade Educator

Problem 36

a. Which of the following water-soluble proteins would have the greatest percentage of polar amino acids-a spherical protein, a cigar-shaped protein, or a subunit of a hexamer?
b. Which of these would have the smallest percentage of polar amino acids?

Zubair Abdulla

Numerade Educator

Problem 37

Unlike most amines and carboxylic acids, amino acids are insoluble in diethyl ether. Explain.

Nima Gharibi

Numerade Educator

Problem 38

Indicate the peptides that would result from cleavage by the indicated reagent:
a. His-Lys-Leu-Val-Glu-Pro-Arg-Ala-Gly-Ala by trypsin
b. Leu-Gly-Ser-Met-Phe-Pro-Tyr-Gly-Val by chymotrypsin
c. Val-Arg-Gly-Met-Arg-Ala-Ser by carboxypeptidase A
d. Ser-Phe-Lys-Met-Pro-Ser-Ala-Asp by cyanogen bromide
e. Arg-Ser-Pro-Lys-Lys-Ser-Glu-Gly by trypsin

Zubair Abdulla

Numerade Educator

Problem 39

Aspartame has a pI of $5.9 .$ Draw its most prevalent form at physiological pH.

Tyler Walter

Numerade Educator

Problem 40

Draw the form of aspartic acid that predominates at
a. $\quad \mathrm{pH}=1.0$
b. $\quad \mathrm{pH}=2.6$
c. $\quad \mathrm{pH}=6.0$
d. $\quad \mathrm{pH}=11.0$

Tyler Walter

Numerade Educator

Problem 41

Dr. Kim S. Tree was preparing a manuscript for publication in which she reported that the pI of the tripeptide Lys-Lys-Lys was. 10.6. One of her students pointed out that there must be an error in her calculations because the $\mathrm{p} K_{\mathrm{a}}$ of the $\varepsilon$ -amino group of lysine is 10.8 and the pI of the tripeptide has to be greater than any of its individual $\mathrm{p} K_{\mathrm{a}}$ values. Was the student correct?

Zubair Abdulla

Numerade Educator

Problem 42

A mixture of amino acids that do not separate sufficiently when a single technique is used can often be separated by two-dimensional chromatography. In this technique, the mixture of amino acids is applied to a piece of filter paper and separated by chromatographic techniques. The paper is then rotated $90^{\circ},$ and the amino acids are further separated by electrophoresis, producing a type of chromatogram called a fingerprint. Identify the spots in the fingerprint obtained from a mixture of Ser, Glu, Leu, His, Met, and Thr.

Zubair Abdulla

Numerade Educator

Problem 43

Explain the difference in the $\mathrm{p} K_{\mathrm{a}}$ values of the carboxyl groups of alanine, serine, and cysteine.

Zubair Abdulla

Numerade Educator

Problem 44

Which would be a more effective buffer at physiological pH, a solution of $0.1 \mathrm{M}$ glycylglycylglycylglycine or a solution of $0.2 \mathrm{M}$ glycine?

Zubair Abdulla

Numerade Educator

Problem 45

Identify the location and type of charge on the hexapeptide Lys-Ser-Asp-Cys-His-Tyr at
a. $\mathrm{pH}=7$
b. $\mathrm{pH}=5$
c. $\mathrm{pH}=9$

Zubair Abdulla

Numerade Educator

Problem 46

The following polypeptide was treated with 2 -mercaptoethanol and then with iodoacetic acid. After reacting with maleic anhydride, the peptide was hydrolyzed by trypsin. (Treatment with maleic anhydride causes trypsin to cleave a peptide only at arginine residues.)
Gly-Ser-Asp-Ala-Leu-Pro-Gly-Ile-Thr-Ser-Arg-Asp-Val-Ser-Lys-Val-Glu-Tyr-Phe-Glu-Ala-Gly-Arg-Ser-Glu-Phe-Lys-Glu-ProArg-Leu-Tyr-Met-Lys-Val-Glu-Gly-Arg-Pro-Val-Ser-Ala-Gly-Leu-Trp
a. Why, after a peptide is treated with maleic anhydride, does trypsin no longer cleave it at lysine residues?
b. How many fragments are obtained from the peptide?
c. In what order would the fragments be eluted from an anion-exchange column using a buffer of $\mathrm{pH}=5 ?$

Zubair Abdulla

Numerade Educator

Problem 47

Treatment of a polypeptide with 2 -mercaptoethanol yields two polypeptides with the following primary sequences:
Val-Met-Tyr-Ala-Cys-Ser-Phe-Ala-Glu-Ser
Ser-Cys-Phe-Lys-Cys-Trp-Lys-Tyr-Cys-Phe-Arg-Cys-Ser
Treatment of the original intact polypeptide with chymotrypsin yields the following peptides:
a. Ala, Glu, Ser
b. 2 Phe, 2 Cys, Ser
c. Tyr, Val, Met
d. Arg, Ser, Cys
e. Ser, Phe, 2 Cys, Lys, Ala, Trp
f. Tyr, Lys
Determine the positions of the disulfide bridges in the original polypeptide.

Susan Hallstrom

Susan Hallstrom

Numerade Educator

Problem 48

Show how aspartame can be synthesized using DCC.

Zubair Abdulla

Numerade Educator

Problem 49

Reaction of a polypeptide with carboxypeptidase A releases Met. The polypeptide undergoes partial hydrolysis to give the following peptides. What is the sequence of the polypeptide?
a. Ser, Lys, Trp
b. Gly, His, Ala
c. Glu, Val, Ser
d. Leu, Glu, Ser
e. Met, Ala, Gly
f. Ser, Lys, Val
g. Glu, His
h. Leu, Lys, Trp
i. Lys, Ser
j. Glu, His, Val
k. Trp, Leu, Glu
I. Ala, Met

Zubair Abdulla

Numerade Educator

Problem 50

Glycine has $\mathrm{p} K_{\mathrm{a}}$ values of 2.3 and $9.6 .$ Would you expect the $\mathrm{p} K_{\mathrm{a}}$ values of glycylglycine to be higher or lower than these values?

Zubair Abdulla

Numerade Educator

Problem 51

A mixture of 15 amino acids gave the fingerprint shown in the below (see also Problem 42 ). Identify the spots. (Hint 1 : Pro reacts with ninhydrin to form a yellow color; Phe and Tyr form a yellow-green color. Hint 2: Count the number of spots before you start.)

Zubair Abdulla

Numerade Educator

Problem 52

Dithiothreitol reacts with disulfide bridges in the same way that 2 -mercaptoethanol does. With dithiothreitol, however, the equilibrium lies much more to the right. Explain.

Zubair Abdulla

Numerade Educator

Problem 53

$\alpha$ -Amino acids can be prepared by treating an aldehyde with ammonia and hydrogen cyanide, followed by acid-catalyzed hydrolysis.
a. Give the structures of the two intermediates formed in this reaction.
b. What amino acid is formed when the aldehyde that is used is 3 -methylbutanal?
c. What aldehyde would be needed to prepare valine?

Ronald Prasad

Numerade Educator

Problem 54

The UV spectra of tryptophan, tyrosine, and phenylalanine are shown here. Each spectrum is that of a $1 \times 10^{-3} \mathrm{M}$ solution of the amino acid, buffered at $\mathrm{pH}=6.0 .$ Calculate the approximate molar absorptivity of each of the three amino acids at $280 \mathrm{nm}$.

Aadit Sharma

Numerade Educator

Problem 55

A normal polypeptide and a mutant of the polypeptide were hydrolyzed by an endopeptidase under the same conditions. The normal and mutant differ by one amino acid residue. The fingerprints of the peptides obtained from the normal and mutant polypeptides are as shown. What kind of amino acid substitution occurred as a result of the mutation (That is, the substituted amino acid more or less polar than the original amino acid? Is its pI lower or higher?)

Zubair Abdulla

Numerade Educator

Problem 56

Determine the amino acid sequence of a polypeptide from the following results:
a. Complete hydrolysis of the peptide yields the following amino acids: Ala, Arg, Gly, 2 Lys, Met, Phe, Pro, 2 Ser, Tyr, Val.
b. Treatment with Edman's reagent gives PTH-Val.
c. Carboxypeptidase A releases Ala.
d. Treatment with cyanogen bromide yields the following two peptides:
1. Ala, 2 Lys, Phe, Pro, Ser, Tyr
2. Arg, Gly, Met, Ser, Val
e. Treatment with chymotrypsin yields the following three peptides:
1. 2 Lys, Phe, Pro
2. Arg, Gly, Met, Ser, Tyr, Val
3. Ala, Ser
f. Treatment with trypsin yields the following three peptides:
1. Gly, Lys, Met, Tyr
2. Ala, Lys, Phe, Pro, Ser
3. Arg, Ser, Val

Zubair Abdulla

Numerade Educator

Problem 57

The C-terminal end of a protein extends into the aqueous environment surrounding the protein. The C-terminal amino acids are Gln, Asp, 2 Ser, and three nonpolar amino acids. Assuming that the $\Delta G^{\circ}$ for formation of a hydrogen bond is -3 kcal/mol and the $\Delta G^{\circ}$ for removal of a hydrophobic group from water is $-4 \mathrm{kcal} / \mathrm{mol},$ calculate the $\Delta G^{\circ}$ for folding the C-terminal end of the
a. All the polar groups form one intramolecular hydrogen bond.
b. All but two of the polar groups form intramolecular hydrogen bonds.

Ramesh Singh

Numerade Educator

Problem 58

Professor Mary Gold wanted to test her hypothesis that the disulfide bridges that form in many proteins do so after the minimum energy conformation of the protein has been achieved. She treated a sample of lysozyme, an enzyme containing four disulfide bridges, with 2-mercaptoethanol and then added urea to denature the enzyme. She slowly removed these reagents so that the enzyme could refold and reform the disulfide bridges. The lysozyme she recovered had $80 \%$ of its original activity. What would be the percent activity in the recovered enzyme if disulfide bridge formation were entirely random rather than determined by the tertiary structure? Does this experiment support Professor Gold's hypothesis?

Zubair Abdulla

Numerade Educator