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Organic Chemistry

Marc Loudon, Jim Parise

Chapter 27

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

Educators

Chapter Questions

01:05

Problem 1

Draw the structure of
(a) 4 -(dimethylamino)pyridine
(b) 4 -ethyl-2-nitroimidazole

Grigoriy Sereda
Grigoriy Sereda
Numerade Educator
04:10

Problem 1

Draw the structures of the following peptides.
(a) tryptophylglycylisoleucylaspartic acid
(b) Glu-Gln-Phe-Arg (or E-Q-F-R)

Susan Hallstrom
Susan Hallstrom
Numerade Educator
03:09

Problem 2

Name the following compounds.

Nicholas Sacco
Nicholas Sacco
Numerade Educator
01:23

Problem 2

Using three-letter abbreviations for the amino acid residues, name the following peptide.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
02:02

Problem 3

Draw the important resonance structures for pyrrole.

Amy Jiang
Amy Jiang
Numerade Educator
02:09

Problem 3

Draw condensed structures for each of the following:
(a) a phenylalanine residue in a large protein
(b) a serine residue in an enzyme

Lijeesh Krishnan
Lijeesh Krishnan
Numerade Educator
02:03

Problem 4

(a) The dipole moments of pyrrole and pyrrolidine are similar in magnitude but have opposite directions. Explain, indicating the direction of the dipole moment in each compound.
(b) Explain why the dipole moments of furan and pyrrole have opposite directions.
(c) Should the dipole moment of 3,4 -dichloropyrrole be greater than or less than that of pyrrole? Explain.

Raghvendra Singh
Raghvendra Singh
Numerade Educator
02:42

Problem 4

Draw three valid line-and-wedge general structures for naturally occurring $\alpha$ -amino acids in addition to the ones shown in this section.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
02:22

Problem 5

Each of the following NMR chemical shifts goes with a proton at carbon-2 of either pyridine, pyrrolidine, or pyrrole. Match each chemical shift with the appropriate heterocyclic compound, and explain your answer: $\delta 8.51 ; \delta 6.41 ;$ and $\delta 2.82$.

Zubair Abdulla
Zubair Abdulla
Numerade Educator
04:13

Problem 5

(a) L-Isoleucine has two asymmetric carbons and has the $2 S, 3 S$ configuration. Complete the following line-and-wedge structure for $\mathrm{L}$ -isoleucine.
(b) Alloisoleucine is the diastereomer of isoleucine. Complete the line-and-wedge structure in part (a) for D-alloisoleucine.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
01:32

Problem 6

(a) What is the $\alpha$ -carbon configuration of $\mathrm{L}$ -cysteine in the $R, S$ system?
(b) Explain why $\mathrm{L}$ -cysteine and $\mathrm{L}$ -serine have different configurations in the $R, S$ system.

Grigoriy Sereda
Grigoriy Sereda
Numerade Educator
08:58

Problem 7

Obtain the three $\mathrm{p} K_{\mathrm{a}}$ values of the $\alpha$ -amino acid histidine from Table 27.1. Because there are three $\mathrm{p} K_{\mathrm{a}}$ values, the dissociation equilibria contain four species.
(a) With the species present at low $\mathrm{pH}$ on the left, and the fully dissociated species on the right, draw and label by letter all of the species involved in the acid-base dissociation equilibria of histidine. (Hint: The side-chain group protonates on the vinylic nitrogen of the imidazole ring.)
(b) Sketch a graph similar to Fig. 27.1 in which the fraction of all of the species are shown as a function of $\mathrm{pH}$. Label each curve with a letter corresponding to one of the forms you drew in part (b). Indicate the pH values at which the fractions of two species are equal.

Rashmi Sinha
Rashmi Sinha
Numerade Educator
03:40

Problem 8

(a) Point out the ionizable groups of the amino acid tyrosine (Table 27.1).
(b) What is the net charge on tyrosine at $\mathrm{pH} 6$ ? How do you know?
(c) Draw the structure of the major form(s) of tyrosine present at this pH.

Charles Thomas
Charles Thomas
Numerade Educator
04:20

Problem 9

(a) Estimate the isoelectric point of each of the following peptides. $\begin{array}{ll}\text { A-K-V-I-M } & \text { G-D-G-L-F }\end{array}$
(b) Draw the structures of these peptides, indicating the predominant ionization state of each at its isoelectric point.

Ronald Prasad
Ronald Prasad
Numerade Educator
03:20

Problem 10

Classify the following peptides as acidic, basic, or neutral. What is the net charge on each peptide at $\mathrm{pH}=6 ?$
(a) Gly-Leu-Val
(b) Leu-Trp-Lys-Gly-Lys
(c) $N$ -acetyl-Asp-Val-Ser-Arg-Arg ( $N$ -acetyl means that the terminal amino group of the peptide is acetylated.)
(d) Glu-Lys-Asp-Ala-Phe-Ile

Ramesh Singh
Ramesh Singh
Numerade Educator
04:31

Problem 11

(a) How might the structure of the resin in Eq. 27.9 be altered to make the resin an anion exchanger (that is, an anion-binding resin)? (Hint: What type of organic functional group carries a positive charge at neutral pH?)
(b) Predict the order of elution of the following peptides from an anion-exchange resin at $\mathrm{pH}$ 6: $\mathrm{A}-\mathrm{V}-\mathrm{G}, \mathrm{D}-\mathrm{E}-\mathrm{E}-\mathrm{G}, \mathrm{D}-\mathrm{N}-\mathrm{N}-\mathrm{G}$. Explain your reasoning.

Ian Kaigh
Ian Kaigh
Numerade Educator
04:11

Problem 12

Indicate which of the methods in this section can be used to prepare each of the following amino acids. For each method that can be used, give an equation. For each case in which a method would not work, give a reason.
(a) $\alpha$ -phenylglycine
(b) leucine

Dalton Hilovsky
Dalton Hilovsky
Numerade Educator
07:27

Problem 13

Draw the structure of the major product expected when
(a) leucine is treated with $p$ -toluenesulfonyl chloride (tosyl chloride).
(b) alanine is heated in methanol solvent with HCl catalyst.

Vishal Sharma
Vishal Sharma
Numerade Educator
01:53

Problem 14

If the hydrochloride salt of glycine methyl ester is neutralized and allowed to stand in solution, a polymer forms. If the hydrochloride itself is allowed to stand, the polymerization reaction does not occur. Explain these observations by writing the reaction that occurs.

Tom Rutherford
Tom Rutherford
Numerade Educator
04:01

Problem 15

Calculate the average yield of each of the 369 steps in the synthesis of ribonuclease by the solid-phase method discussed in the sidebar on p. 1391, assuming the reported overall yield of $17 \%$.

Caroline Basil
Caroline Basil
Numerade Educator
04:06

Problem 16

What average yield per amino acid would be required to synthesize a protein containing 100 amino acids in $50 \%$ overall yield?

Zubair Abdulla
Zubair Abdulla
Numerade Educator
05:10

Problem 17

(a) Arrange the following esters in order of increasing reactivity toward glycinamide (the amide of the amino acid glycine), least reactive first, and explain your choice.
a
b
c
d

Tom Rutherford
Tom Rutherford
Numerade Educator
07:26

Problem 18

(a) An aspiring peptide chemist, Mo Bonds, has decided to attempt the synthesis of the peptide Gly-Lys-Ala using the solid-phase method. To the Ala-resin he couples the following derivative of lysine:
Why are $t w o$ protecting groups necessary for lysine?
(b) After the coupling, he deprotects his resin-bound peptide with $20 \%$ piperidine in DMF, and then completes the synthesis in the usual way by coupling Fmoc-Gly, deprotecting the peptide, and removing it from the resin. He is shocked to find a mixture of several peptide products. Two of them contain one residue of each of the amino acids Ala, Gly, and Lys, and one contains two residues of Gly, one residue of Ala, and one residue of Lys. Suggest a structure for each product and explain how each is formed.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
11:28

Problem 19

Consider the following solid-phase peptide synthesis:
(a) Give the structure of each compound $A-E$ and $P$.
(b) Explain the reason for the Boc group on the side chain of the Lys group in the reaction $B \longrightarrow C$.
(c) Explain why Boc-Val rather than Fmoc-Val is used in the $D \longrightarrow E$ step of the synthesis.

Nima Gharibi
Nima Gharibi
Numerade Educator
06:13

Problem 20

(a) Give all of the mRNA codes for the peptide Phe-Arg-Gly-His-Trp.
(b) What are the DNA codes for the same peptide?
(c) What is the anticodon sequence in the tRNA for the Trp residue? (Hint: Be sure to specify the direction.)

Susan Hallstrom
Susan Hallstrom
Numerade Educator
06:13

Problem 21

In some tRNAs the anticodon contains an inosine. The heterocyclic base in inosine is hypoxanthine.
Inosine can form hydrogen-bonded base pairs with $\mathrm{A}, \mathrm{U},$ or $\mathrm{C}$. This means that the inosine in tRNA can pair any of these bases in mRNA. Show the hydrogen-bonded base pair of hypoxanthine
(a) with adenine;
(b) with uracil.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
04:21

Problem 22

(a) Notice in peptide $P$ (see previous discussion) that Asn and Asp are not distinguished by amino acid analysis. Explain. (Hint: Why is ammonia present in the amino acid analysis of peptide $P ?)$
(b) What other pair of amino acids are not differentiated by amino acid analysis?

Susan Hallstrom
Susan Hallstrom
Numerade Educator
03:21

Problem 23

AQC-tryptophan is not shown in Fig. 27.5 because the indole ring does not survive the acid hydrolysis. In what general region of the chromatogram would you expect to find $\mathrm{AQC}$ -Trp if it were present? Explain.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
06:47

Problem 24

The amino acids Lys and Cys, after "tagging" with $\mathrm{AQC},$ are each found to contain $t w o \mathrm{AQC}$ groups. Explain; your explanation should involve the structures of the $\mathrm{AQC}$ -amino acids.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
04:11

Problem 25

A peptide $P$ has the sequence of amino acids E-R-G-A-N-I-K-K-H-E-M. What products would be formed if this peptide were subjected to trypsin-catalyzed hydrolysis?

Susan Hallstrom
Susan Hallstrom
Numerade Educator
11:34

Problem 26

When a peptide $Q$ with the amino acid analysis (A,F,G $_{2}$, I, K,N,P,R,S,Y) is treated with trypsin, three new peptides are formed (amino acid analysis in parentheses): $T 1(\mathrm{~A}, \mathrm{~F}, \mathrm{R}, \mathrm{S}) ; T 2(\mathrm{G}, \mathrm{I}, \mathrm{K}) ;$ and $T 3(\mathrm{G}, \mathrm{N}, \mathrm{P}, \mathrm{Y})$. When peptide $Q$ is treated with chymotrypsin, four peptides are formed: $C I(\mathrm{~A}, \mathrm{~N}, \mathrm{R}, \mathrm{S}, \mathrm{Y}) ; C 2(\mathrm{~F}, \mathrm{~K}) ; C 3(\mathrm{G}, \mathrm{I}) ;$ and $C 4(\mathrm{G}, \mathrm{P}) .$ What can you deduce about the order in which the
amino acids in $P$ are connected? Explain. What are the points of uncertainty?

Susan Hallstrom
Susan Hallstrom
Numerade Educator
07:39

Problem 27

(a) Give the $m / z$ values of the fragment ions expected from b-type fragmentation of an $M+1$ ion of the peptide $N-F-E-S-G-K$.
(b) Give the $m / z$ values of the fragment ions expected from y-type fragmentation of an $M+1$ ion of the peptide in part (a). All y-type fragments contain a protonated terminal amino group; that is, $\mathrm{H}_{3} \mathrm{~N}^{+}-$.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
12:06

Problem 28

Give the curved-arrow mechanism for the formation of each of the following fragment ions in Fig. 27.7 from an $\mathrm{M}+1$ ion.
(a) the fragment at $m / z=551.94$. [Hint: This fragment results from an a-type cleavage (Eq. 27.39).]
(b) the fragment ion at $m / z=710.97$
(c) the fragment ion at $727.09 .$ Show how this mechanism might be tested with a deuterium-labeled peptide.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
09:33

Problem 29

Using the curved-arrow notation, write in detail the mechanisms for the reactions in
(a) Eq. $27.42 \mathrm{a}$
(b) Eq. $27.42 \mathrm{~b}$
(c) Eq. $27.42 \mathrm{c}$

Susan Hallstrom
Susan Hallstrom
Numerade Educator
02:58

Problem 30

Some peptides found in nature have an amino-terminal acetyl group (red):
(a) Can these peptides undergo the Edman degradation? Explain.
(b) Does $N$ -acylation have any adverse effect on sequencing by MS-MS? Explain.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
02:58

Problem 31

(a) Draw the structure of a phosphotyrosine residue.
(b) Would the equilibrium constant for formation of a phosphotyrosine residue from ATP (by a reaction analogous to the one shown in Eq. 27.43 ) be greater than, less than, or about the same as $K_{\text {eq }}$ for the phosphorylation of a serine residue? Explain.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
01:26

Problem 32

Draw the structure of a phosphocysteine residue that shows the configuration on the asymmetric carbons with lines and wedges.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
03:38

Problem 33

Using abbreviated structures, draw the structure of an $N$ -acetylgalactosamine conjugate with a threonine residue of an acceptor protein formed with inversion of configuration at the anomeric carbon.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
05:09

Problem 34

(a) Draw a resonance structure for the carbocation intermediate in Eq. 27.48 .
(b) All of the enzyme-catalyzed glycosylations require $\mathrm{Mn}^{2+}$, a divalent cation. Suggest a role for the metal ion in the glycosylation mechanism.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
04:55

Problem 35

Draw a curved-arrow mechanism for the Amadori rearrangement in Eq. 27.50. Let $\mathrm{H}_{3} \mathrm{O}^{+}$ and $\mathrm{H}_{2} \mathrm{O}$ be the acid-base pair, present as necessary.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
03:33

Problem 36

It is possible to envision an Amadori rearrangement of an $N$ -glycoside formed at an asparagine amide-NH $_{2}$ group. In fact, this does not occur because the imine required for the rearrangement does not form. Use the mechanism of imine formation to explain why. (The inability of asparagine $N$ -glycosides to undergo this reaction is probably why asparagine rather than lysine evolved as the amino acid residue involved in $N$ -glycoside formation.)

Susan Hallstrom
Susan Hallstrom
Numerade Educator
06:59

Problem 37

When the formation of HbAlc reverses, not only glucose, but also mannose, is formed. Explain the origin of the mannose.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
04:11

Problem 38

What would you expect to happen when hemoglobin is treated with a denaturant such as $8 M$ urea? Explain.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
02:58

Problem 39

Aeruginosin-B is a recently discovered natural product that inhibits trypsin.
Postulate one structural reason that aeruginosin-B binds to trypsin. Explain.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
03:57

Problem 40

Eq. 27.53 shows the first step in the curved-arrow mechanism of peptide hydrolysis catalyzed by HIV protease. Complete the mechanism, using the two aspartic acid residues as catalytic groups.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
03:13

Problem 41

The scientists who developed Norvir stated that one of the significant interactions of the inhibitor with the enzyme is hydrogen bonding of a thiazole nitrogen (the thiazole on the right side of the structure on p. 1438 ) with a backbone $\mathrm{N}-\mathrm{H}$ of a nearby peptide bond on the enzyme. Draw a thiazole such as the one in Norvir and, using it, show such a hydrogen-bonding interaction.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
02:16

Problem 42

Show all of the potential hydrogen-bonding sites of Darunavir; explain whether they are acceptor or donor sites.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
14:08

Problem 43

Give the structures of the products expected when (1) valine and (2) proline (or other compounds indicated) react with each of the following reagents:
(a) ethanol (solvent), $\mathrm{H}_{2} \mathrm{SO}_{4}$ catalyst
(b) benzoyl chloride, $\mathrm{Et}_{3} \mathrm{~N}$
(c) aqueous $\mathrm{HCl}$ solution
(d) aqueous $\mathrm{NaOH}$ solution
(e) benzaldehyde, heat, $\mathrm{NaCN}$
(f) Fmoc-NHS ester, $\mathrm{Na}_{2} \mathrm{CO}_{3}$, aqueous 1,2 -dimethoxyethane, then neutralize with $\mathrm{H}_{3} \mathrm{O}^{+}$
(g) product of part (f) $+\mathrm{DIC} / \mathrm{HOBt}+$ glycine tert-butyl ester
(h) product of part (g) + anhydrous $\mathrm{CF}_{3} \mathrm{CO}_{2} \mathrm{H}$
(i) product of part (h) $+20 \%$ piperidine in DMF
(j) product of part (i) $+6 M$ aqueous HCl, heat

Susan Hallstrom
Susan Hallstrom
Numerade Educator
03:32

Problem 44

Referring to Table 27.1, pp. $1376-1377$, identify the amino acid(s) that satisfy each of the following criteria.
(a) the most acidic amino acid
(b) the most basic amino acid
(c) the amino acids that can exist as diastereomers
(d) the amino acid that has zero optical rotation under all conditions
(e) the amino acids that are converted into other amino acids on treatment with concentrated hot aqueous $\mathrm{NaOH}$ solution followed by neutralization.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
05:54

Problem 45

In repeated attempts to synthesize the dipeptide Val-Leu, aspiring peptide chemist Polly Styreen performs each of the following operations. Explain what, if anything, is wrong with each procedure.
(a) The cesium salt of leucine is allowed to react with chloromethyl resin (as in Eq. 27.21, p. 1393). The resulting derivative is treated with Fmoc-Val and $\mathrm{DIC} / \mathrm{HOBt},$ then with trifluoroacetic acid.
(b) The cesium salt of Fmoc-Leu is allowed to react with the chloromethyl resin. The resulting derivative is then treated with Fmoc-Val and DIC/HOBt, then with trifluoroacetic acid.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
02:50

Problem 46

According to its amino acid composition (Fig. 27.6 ,
p. 1410 ), lysozyme has an isoelectric point that is (choose one and explain):
(1) $\leq<6$
(2) about 6
$(3)>>6$

Susan Hallstrom
Susan Hallstrom
Numerade Educator
02:18

Problem 47

Consider the following two peptides, which may have been isolated from the floor of a Big Ten basketball arena circa 2000:
$A: \quad \mathrm{K}-\mathrm{E}-\mathrm{A}-\mathrm{D}-\mathrm{Y}$
$\begin{array}{ll}B: & \mathrm{K}-\mathrm{N}-\mathrm{I}-\mathrm{G}-\mathrm{H}-\mathrm{T}\end{array}$
(a) Which peptide is more basic (has the higher isoelectric point)? Explain.
(b) Which peptide will emerge first from an anionexchange column at $\mathrm{pH}=6.0 ?$
(c) Which one of the following nucleotide sequences (3'-end on the left) could be the DNA sequence that codes for the biosynthesis of peptide $A ?$ Explain your reasoning.
Sequence 1: CGUGAAGCCGACUACUAA Sequence 2: TTCCTTCGGCTGATA Sequence 3 : ATTATGGTGCGGGATGCA
Sequence 4: GCACUUCGGCUGAUGAUU

Susan Hallstrom
Susan Hallstrom
Numerade Educator
01:08

Problem 48

Which of the following statements would correctly describe the isoelectric point of cysteic acid, an oxidation product of cysteine? Explain your answer.
(1) lower than that of aspartic acid
(2) about the same as that of aspartic acid
(3) about the same as that of cysteine
(4) about the same as that of lysine
(5) higher than that of lysine

Susan Hallstrom
Susan Hallstrom
Numerade Educator
02:29

Problem 49

A peptide was subjected to one cycle of the Edman degradation, and the following compound was obtained. What is the amino-terminal residue of the peptide?

Susan Hallstrom
Susan Hallstrom
Numerade Educator
04:02

Problem 50

Dansyl chloride (5-dimethylamino-1-naphthalenesulfonyl chloride) reacts with amino groups to give a fluorescent derivative. After a peptide $P$ with the composition (Arg,Asp,Gly,Leu $_{2}$,Thr,Val) reacts with dansyl chloride at $\mathrm{pH} 9$, it is hydrolyzed in $6 \mathrm{M}$ aqueous $\mathrm{HCl}$. The derivative shown in the equation given in Fig. $\mathrm{P} 27.50$, detected by its fluorescence, is isolated after neutralization, along with the free amino acids Arg, Asp, Gly, Leu, and Thr. What conclusion can be drawn about the structure of the peptide from this result?

Susan Hallstrom
Susan Hallstrom
Numerade Educator
01:42

Problem 51

A peptide Q has the following composition by amino acid analysis:
Treatment of $Q$ once with the Edman reagent followed by anhydrous acid gives a new peptide $R$ with the following composition by amino acid analysis:
$R: \quad \mathrm{Ala}, \mathrm{Arg}, \mathrm{Asp}, \mathrm{Gly}_{2}, \mathrm{Glu}, \mathrm{Val}_{2}, \mathrm{NH}_{3}$
Treatment of $Q$ and $R$ with the enzyme dipeptidylaminopeptidase (DPAP) yields a mixture of the following peptides:
$Q \quad \stackrel{\text { DPAP }}{\longrightarrow}$ Arg-Gly, Gln-Ala, Leu-Val, Val-Asp, Gly
$R \stackrel{\mathrm{DPAP}}{\longrightarrow}$ Ala-Gly, Asp-Gln, Gly-Val, Val-Arg
What is the amino acid sequence of $Q$ ?

Susan Hallstrom
Susan Hallstrom
Numerade Educator
07:41

Problem 52

The peptide hormone glucagon has the following amino acid sequence:

His-Ser-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Lys-TyrLeu-Asp-Ser-Arg-Arg-Ala-Gln-Asp-Phe-Val-Gln-TrpLeu-Met-Asn-Thr

Give the products that would be obtained when this protein is treated with
(a) trypsin at pH 8
(b) $\mathrm{Ph}-\mathrm{N}=\mathrm{C}=\mathrm{S},$ then $\mathrm{CF}_{3} \mathrm{CO}_{2} \mathrm{H},$ then aqueous acid

Susan Hallstrom
Susan Hallstrom
Numerade Educator
07:26

Problem 53

A peptide $C$ was found to have a molecular mass of about
1000. Amino acid analysis of $C$ revealed its composition to be $\left(\mathrm{Ala}_{2}, \mathrm{Arg}, \mathrm{Gly}, \mathrm{Ile}\right)$. The peptide was unchanged on treatment with the Edman reagent, then $\mathrm{CF}_{3} \mathrm{CO}_{2} \mathrm{H}$. Treatment of $C$ with trypsin gave a single peptide $D$ with an amino acid analysis identical to that of $C$. Three cycles of the Edman degradation applied to $D$ revealed the partial sequence Ala-Ile-Gly.
(a) Suggest a structure for peptide $C$ and explain how you arrived at that structure.
(b) Describe what you would expect to see for the b-type fragmentation of the $\mathrm{M}+1$ ion of both peptides $C$ and $D$ in MS-MS.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
08:14

Problem 54

When bovine insulin is treated with the Edman reagent followed by anhydrous $\mathrm{CF}_{3} \mathrm{CO}_{2} \mathrm{H},$ then by aqueous acid, the PTH derivatives of both glycine and phenylalanine are obtained in nearly equal amounts. What can be deduced about the structure of insulin from this information?

Susan Hallstrom
Susan Hallstrom
Numerade Educator
02:21

Problem 55

An amino acid $A$, isolated from the acid-catalyzed hydrolysis of a peptide antibiotic, gave a positive test with ninhydrin and had a specific optical rotation (HCl solution) of $+37.5^{\circ} \mathrm{mL} \mathrm{g}^{-1} \mathrm{dm}^{-1}$. Compound $A$ was not identical to any of the amino acids in Table 27.1, pp. $1376-1377$. The isoelectric point of compound $A$ was found to be 9.4 . Compound $A$ could be prepared by the reaction of $\mathrm{L}$ -glutamine with $\mathrm{Br}_{2}$ in $\mathrm{NaOH}$, followed by neutralization. (See Sec. 23.11D.) Suggest a structure for $A$.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
02:00

Problem 56

A previously unknown amino acid, $\gamma$ -carboxyglutamic acid (Gla), was discovered to be a posttranslational modification in the amino acid sequence of the blood-clotting protein prothrombin.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
02:14

Problem 56

A previously unknown amino acid, $\gamma$ -carboxyglutamic acid (Gla), was discovered to be a posttranslational modification in the amino acid sequence of the blood-clotting protein prothrombin.
This amino acid escaped detection for many years because, on acid hydrolysis, it is converted into another common amino acid. Explain.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
06:09

Problem 57

(a) What reagent would be used to convert the corresponding chloromethyl polystyrene resin into the following resin?
(b) To a column containing this resin suspended in a pH 6 buffer is added a mixture of the amino acids Arg, Glu, and Leu, and the column is eluted with the same buffer. In what order will the amino acids emerge from the column? Explain.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
05:30

Problem 58

In paper electrophoresis, amino acids and peptides can be separated by their differential migration in an electric field. To the center of a strip of paper is applied a mixture of the following three peptides in a single small spot:
Gly-Lys, Gly-Asp, and Gly-Ala. The paper is soaked in a $\mathrm{pH}=6$ buffer, a positively charged electrode (anode) is attached to the left side of the paper, and a negatively charged electrode (cathode) is attached to the right side. A voltage is applied across the ends of the paper for a time, after which the peptides have separated into three spots:
one near the cathode, one near the anode, and one in the center, at the location of the original spot. Which peptide is in each spot? Explain.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
05:49

Problem 59

When a mixture of the amino acids Phe and Gly is subjected to chromatography in a pH 6 buffer on the ion-exchange resin shown in Eq. 27.9 on p. $1386,$ the Phe emerges from the column much later than the Gly, even though the two amino acids have the same isoelectric point. Explain.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
01:42

Problem 60

Suppose a mixture of $\mathrm{AQC}$ -amino acids is subjected to HPLC on a stationary phase that consists of C8-silica rather than C18-silica; that is, the glass stationary phase (Eq. 27.35, p. 1406) contains covalently attached octyl groups rather than octadecyl groups. Assuming all other conditions are the same, how would this change affect the separation of the $\mathrm{AQC}$ -amino acids? Explain.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
15:55

Problem 61

Explain each of the following observations.
(a) The optical rotations of alanine are different in water, $1 \mathrm{M} \mathrm{HCl}$, and $1 \mathrm{M} \mathrm{NaOH}$.
(b) Two mono- $N$ -acetyl derivatives of lysine are known.
(c) The peptide Gly-Ala-Arg-Ala-Glu is readily hydrolyzed by trypsin in water at $\mathrm{pH}=8$, but it is inert to trypsin in $8 M$ urea at the same $\mathrm{pH}$.
(d) After peptides containing cysteine are treated with $\mathrm{HSCH}_{2} \mathrm{CH}_{2} \mathrm{OH},$ then with aziridine, they can be cleaved by trypsin at their (modified) cysteine residues.
(e) When L-methionine is oxidized with $\mathrm{H}_{2} \mathrm{O}_{2},$ two separable methionine sulfoxides with the following structure are formed:

Susan Hallstrom
Susan Hallstrom
Numerade Educator
04:00

Problem 62

(a) When proteins are prepared for sequencing, they are treated with DTT (Eq. $27.38,$ p. 1409 ) and then with an excess of iodoacetic acid, $\mathrm{I}-\mathrm{CH}_{2}-\mathrm{CO}_{2} \mathrm{H},$ at $\mathrm{pH}=8-9 .$ Explain how iodoacetic acid reacts with the side-chain thiol group of a cysteine residue, and why this reaction is a necessary prelude to sequencing.
(b) Another reaction that accomplishes the same objective is oxidation of the disulfide bonds with $\mathrm{H}_{2} \mathrm{O}_{2}$. What is the product of this oxidation?

Susan Hallstrom
Susan Hallstrom
Numerade Educator
03:12

Problem 63

One posttranslational side-chain modification of proteins is the methylation of aspartic acid residues to give a sidechain Asp-methyl ester. Draw the structure of this residue, and indicate what coenzyme is involved in this reaction. (Hint: See Sec. 11.7B.)

Susan Hallstrom
Susan Hallstrom
Numerade Educator
05:47

Problem 64

Sometimes preparations of chymotrypsin are contaminated with small amounts of trypsin. This can be a problem if the specific hydrolysis of peptides with only chymotrypsin is desired. How could trypsin-catalyzed hydrolysis with this chymotrypsin-trypsin mixture be avoided without having to separate the two enzymes?

Susan Hallstrom
Susan Hallstrom
Numerade Educator
06:06

Problem 65

Sometimes it is necessary in solid-phase peptide synthesis to use a resin linker that is more sensitive (that is, more reactive) to acid than the linker shown in Eq. 27.20 on
p. 1393 . The following group (blue) is one such linker. Explain why the peptide can be removed from this linker with much more dilute acid than is required for the linker in Eq. $27.20 .$ (Hint: Consider the mechanism in Eq. 27.29 ,
p. $1397 .$ )

Susan Hallstrom
Susan Hallstrom
Numerade Educator
10:27

Problem 66

When either Norvir or Crixivan bind to the active site of HIV protease, the $-\mathrm{OH}$ group in the middle of each molecule is found by X-ray crystallography to displace the tightly bound water present in the free enzyme. (See Eq. $27.53,$ p. $1437 .$.) Show how the two aspartic acid residues of the enzyme could interact with this hydroxy group in such a way that binding of the inhibitor is enhanced.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
09:38

Problem 67

Poly-L-lysine (a peptide containing only lysine residues) exists entirely in an $\alpha$ -helical conformation at $\mathrm{pH}>11$. Below $\mathrm{pH} 10$, however, the peptide becomes a random coil. Poly-L-glutamic acid, on the other hand, exists in the $\alpha$ -helical conformation at $\mathrm{pH}<4,$ but above $\mathrm{pH} 5$ it becomes a random coil. Explain the effect of $\mathrm{pH}$ on the secondary structure of both polymers. That is, explain why low pH destroys the helical conformation of one peptide while high pH destroys the helical conformation of the other. (Hint: Look carefully at the location of the amino acid side chains in Fig. 27.11, p. 1426.)

Susan Hallstrom
Susan Hallstrom
Numerade Educator
07:20

Problem 68

(a) For many years it was difficult to determine the X-ray structures of proteins that are imbedded in membranes because, when they are extracted into an aqueous buffer, they denature. Explain why this denaturation occurs.
(b) In some cases, this denaturation can be prevented by extraction of the protein from the membrane with detergents (Sec. 20.5). Explain.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
02:07

Problem 69

Following is a ribbon diagram for one type of opioid receptor, a family of proteins that bind morphine and other opioids and initiate their physiological effects. The opioid receptor consists mostly of $\alpha$ -helices; the receptor spans the cell membrane. Parts of the helix (R-groups in the following diagram) are adjacent to the lipid bilayer of the membrane.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
02:54

Problem 69

Following is a ribbon diagram for one type of opioid receptor, a family of proteins that bind morphine and other opioids and initiate their physiological effects. The opioid receptor consists mostly of $\alpha$ -helices; the receptor spans the cell membrane. Parts of the helix (R-groups in the following diagram) are adjacent to the lipid bilayer of the membrane.
Which group of amino acid residues are likely to be found in greatest proportion near the phospholipid bilayer (choose one)? Explain why.
A: Asp and Glu
$B:$ Lys, Arg, and His
$C:$ Gly
$D:$ Pro
$E:$ Phe, Leu. Ile, and Val
$F:$ Ser, Thr, Gln, and Asn

Susan Hallstrom
Susan Hallstrom
Numerade Educator
02:54

Problem 70

Complete the reactions given in Fig. $\mathrm{P} 27.70$ assuming the amino acid residue is part of a peptide in aqueous solution and is at neither the amino nor the carboxy terminus.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
02:23

Problem 71

Outline a synthesis of each of the following compounds from the indicated starting material and any other reagents.
a.
b.
c.
d.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
09:07

Problem 72

Show how the acetamidomalonate method can be used to prepare the following unusual amino acids from the indicated starting material and any other reagents.
a.
b.
c.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
09:54

Problem 73

When peptides containing a 2,3-diaminopropanoic acid (DAPA) residue are treated with the Edman reagent and then with acid, a peptide cleavage occurs in addition to degradation of the amino-terminal residue (see Fig. P27.73, p. 1446). Using the curved-arrow notation to rationalize your answer, propose a structure for $X$.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
06:30

Problem 74

The artificial sweetener aspartame (sidebar, p. 1272) was withheld from the market for several years because, on storage for extended periods of time in aqueous solution, it
a.
b.
c.
d.
e.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
12:32

Problem 75

Complete the reactions given in Fig. P27.75 by giving the structure of the major organic product(s).

Susan Hallstrom
Susan Hallstrom
Numerade Educator
12:32

Problem 76

Identify each of the compounds $A-D$ in the reaction scheme shown in Fig. P27.76. Explain your answers.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
35:37

Problem 77

Draw a curved-arrow mechanism for each of the reactions given in Fig. P27.77.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
15:40

Problem 78

When peptides containing the Asn-Gly sequence, such as $H$ in the equation given in Fig. $\mathrm{P} 27.78$ are stored in aqueous solution at neutral or slightly basic solution, ammonia is liberated and a derivative $I$ is formed. On continued storage, species $I$ reacts to give two new peptides: $J$ and $K$. Peptide $J$ is the same as peptide $H$ except that Asn is replaced by Asp, and peptide $K$ is an isomer of peptide $J$. Propose structures for peptides $J$ and $K,$ and rationalize their formation using the curved-arrow notation. (These reactions are believed to be a major source of deterioration associated with aging in naturally occurring peptides and proteins.)

Susan Hallstrom
Susan Hallstrom
Numerade Educator
11:52

Problem 79

In 2007 , scientists in New Zealand isolated a peptide $P$ from enzymatic digests of the pili of gram-positive bacteria. (A pilus is a fibrous appendage that a bacterium uses, among other things, to bind to cells, beginning the process of infection.) This peptide was sequenced by MS-MS, and the following two partial sequences were reconstructed from the mass spectrum:
A: $\mathrm{L}-\mathrm{T}-\mathrm{V}-\mathrm{T}-\mathrm{K}-\mathrm{N}-\mathrm{L}$
$B:$ N-S-L
The mass $\mathrm{M}$ of $P$, deduced from the $m / z$ of its $\mathrm{M}+1$ ion, equaled the mass of $(A+B)-17$ mass units. Two other fragment ions, $C$ and $D$, were also observed. The mass of $C$ equaled the mass of (T-K-N-L + N-S-L) -17 mass units, and the mass of $D$ equaled the mass of $(\mathrm{V}-\mathrm{T}-\mathrm{K}-\mathrm{N}-\mathrm{L}+\mathrm{N}-\mathrm{S}-\mathrm{L})-17$ mass units.
(a) The scientists used these data to propose a primary structure for $P$ that contains an unusual peptide bond. What is this structure? Show how it is consistent with the 17 mass-unit differences.
(b) The scientists also suggested that the unusual peptide bond forms spontaneously by a reaction between two peptide chains within the pilus. Show this reaction and its mechanism.
(c) No such reaction is observed when the peptides $A$ and $B$ are mixed at physiological $\mathrm{pH},$ and, evidently, no enzyme is involved. Why might this reaction nevertheless proceed at a rapid rate within the pilus structure? (Hint: See Sec. 11.8.)

Susan Hallstrom
Susan Hallstrom
Numerade Educator
03:56

Problem 80

(a) In most peptides, the amide bonds have the $Z$ conformation; explain why.
(b) One particular amino acid residue in the Pep $^{C}$ position adopts the $E$ conformation in some cases. Which amino acid residue should be most likely to assume an $E$ conformation, and why?

Susan Hallstrom
Susan Hallstrom
Numerade Educator
08:38

Problem 81

(a) Explain why two monomethyl esters of $N$ -acetyl-Laspartic acid are known. Draw their structures.
(b) Explain why a mixture of these two compounds can be separated by cation-exchange chromatography at $\mathrm{pH}=3.0,$ but not at $\mathrm{pH}=7$. (Hint: Use the $\mathrm{p} K_{\mathrm{a}}$ values of aspartic acid in Table 27.1, pp. $1376-1377 .$ ) Your explanation should indicate which of the two compounds would emerge first from a cation-exchange column at $\mathrm{pH}=3.0 .$ Explain.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
05:30

Problem 82

When $N$ -acetyl-L-aspartic acid is treated with acetic anhydride, an optically active compound $A, \mathrm{C}_{6} \mathrm{H}_{7} \mathrm{NO}_{4},$ is formed. Treatment of $A$ with the amino acid $\mathrm{L}$ -alanine yields two separable, isomeric peptides, $B$ and $C,$ that are both converted into a mixture of $\mathrm{L}$ -alanine and $\mathrm{L}$ -aspartic acid by acid hydrolysis. Suggest structures for $A, B,$ and $C$.

Susan Hallstrom
Susan Hallstrom
Numerade Educator
11:40

Problem 83

Lysozyme (Fig. 27.6, p. 1410) is an antibacterial enzyme that hydrolyzes polysaccharides in bacterial cell walls. It also catalyzes the hydrolysis of a $\beta-1,4$ -linked hexasaccharide oligomer of $N$ -acetylglucosamine into a tetrasaccharide and a disaccharide with retention of stereochemistry, as shown in Fig. P27.83. The active site of lysozyme runs through the enzyme at the junction of the two domains (Fig. 27.13, p. 1428). Near one end of the active site are two aspartic acid residues, Glu- 35 and Asp-52, which are believed to be essential residues involved in the catalysis of hydrolysis. The $\mathrm{p} K_{\mathrm{a}}$ values of the carboxylic acid groups in the side chains of these residues are about 6.0 and 3.5 , respectively. The enzyme functions optimally at $\mathrm{pH}=5$.
(a) Draw a curved-arrow mechanism for the lysozymecatalyzed oligosaccharide hydrolysis at $\mathrm{pH}=5$ shown in Fig. P27.83. Your mechanism should show the roles of the Glu- 35 and Asp-52 carboxylic acid groups, and it should account for the stereochemistry of the reaction.
(b) Treatment of lysozyme with triethyloxonium tetrafluoroborate (pp. $536-537$ ) results in a reaction of the carboxylic acid group of Asp-52 that completely eliminates enzyme activity. What is this reaction? In the light of the mechanism you proposed in (a), account for the effect of this reaction on enzyme activity.

Susan Hallstrom
Susan Hallstrom
Numerade Educator