Consider the structure of the following cyclic octapeptide. Would cleavage of this

Although most naturally occurring proteins are made up only of l amino acids, proteins isolated from bacteria will sometimes contain d amino acids. Draw Fischer projections for d-alanine and d-valine. In each case, assign the configuration (R or S) of the chirality center.

Draw a bond-line structure for each of the following amino acids: (a) l-Leucine (b) l-Tryptophan (c) l-Methionine (d) l-Valine

Of the 20 naturally occurring amino acids shown in Table 25.1, identify any amino acids that exhibit the following: (a) A cyclic structure (b) An aromatic side chain (c) A side chain with a basic group (d) A sulfur atom (e) A side chain with an acidic group (f) A side chain containing a proton that will likely participate in hydrogen bonding

Draw the form of the amino acid that is expected to predominate at the stated pH. (a) Alanine at a pH of 10 (b) Proline at a pH of 10 (c) Tyrosine at a pH of 9 (d) Asparagine at physiological pH (e) Histidine at physiological pH (f) Glutamic acid at a pH of 3

At a pH of 11, arginine is a more effective proton donor than asparagine. Explain.

The OH group on the side chain of serine is not deprotonated at a pH of 12. However, the OH group on the side chain of tyrosine is deprotonated at a pH of 12. This can be verified by inspecting the pKa values in Table 25.2. Suggest an explanation for the difference in acid-base properties between these two OH groups.

Using the data in Table 25.2, calculate the pI of the following amino acids: (a) Aspartic acid (b) Leucine (c) Lysine (d) Proline

For each group of amino acids, identify the amino acid with the lowest pI (try to solve this problem by inspecting their structures, rather than performing calculations). (a) Alanine, aspartic acid, or lysine (b) Methionine, glutamic acid, or histidine

Identify which 2 of the 20 naturally occurring amino acids are expected to have the same pI.

A mixture containing phenylalanine, tryptophan, and leucine was subjected to electrophoresis. Determine which of the amino acids moved the farthest distance assuming that the experiment was performed at the pH indicated: (a) pH 6.0 (b) pH 5.0

Draw the aldehyde that is obtained as a by-product when l-leucine is treated with ninhydrin.

Identify the reagents necessary to make each of the following amino acids using a Hell-Volhard-Zelinsky reaction: (a) Leucine (b) Alanine (c) Valine

Each of the following carboxylic acids was treated with bromine and PBr3 followed by water, and the resulting a-haloacid was then treated with excess ammonia. In each case, draw and name the amino acid that is produced. (a) COOH OH O (b) (c) COOH (d) Acetic acid

Identify the reagents necessary to make each of the following amino acids via the amidomalonate synthesis: (a) Isoleucine (b) Alanine (c) Valine

An amidomalonate synthesis was performed using each of the following alkyl halides. In each case, draw and name the amino acid that was produced. (a) Methyl chloride (b) Isopropyl chloride (c) 2-Methyl-1-chloropropane

Both leucine and isoleucine can be prepared via the amidomalonate synthesis, although one of these amino acids can be produced in higher yields. Identify the higher yield process and explain your choice.

Identify the reagents necessary to make each of the following amino acids using a Strecker synthesis: (a) Methionine (b) Histidine (c) Phenylalanine (d) Leucine

Each of the following aldehydes was converted into an a-amino nitrile followed by hydrolysis to yield an amino acid. In each case, draw and name the amino acid that was produced. (a) Acetaldehyde (b) 3-Methylbutanal (c) 2-Methylpropanal

Identify the starting alkene necessary to make each of the following amino acids using an asymmetric catalytic hydrogenation: (a) l-Alanine (b) l-Valine (c) l-Leucine (d) l-Tyrosine

Explain why it is inappropriate to use a chiral catalyst in the preparation of glycine.

Draw the structure of each of the following peptides: (a) Leu-Ala-Gly (b) Cys-Asp-Ala-Gly (c) Met-Lys-His-Tyr-Ser-Phe-Val

Using three- and one-letter abbreviations, show the sequence of amino acid residues in the following pentapeptide: H2N O H N N H O H N O N H O OH O SH O OH

Determine which of the following peptides will have a higher molecular weight (Hint: It is not necessary to actually calculate the molecular weight of each peptide, but rather, just compare the side chains.) Cys-Tyr-Leu or Cys-Phe-Ile

Compare the following tripeptides and determine whether they are constitutional isomers or the same compound: Ala-Gly-Leu and Leu-Gly-Ala

Draw the s-trans conformation of the dipeptide Phe-Leu and identify both the N terminus and the C terminus.

Draw the s-cis conformation of the dipeptide Phe-Phe and identify the source of the large steric interaction associated with that conformation.

Using a bond-line structure, show the tetrapeptide obtained when two molecules of Cys-Phe are joined by a disulfide bridge.

Aspartame is an artificial sweetener sold under the trade name NutraSweet. Aspartame is the methyl ester of a dipeptide formed from l-aspartic acid and l-phenylalanine and can be summarized as Asp-Phe-OCH3. Surprisingly, the analogous ethyl ester (Asp-PheOCH2CH3) is not sweet. If either l residue is replaced with its enantiomeric d residue, the resulting compound is bitter instead of sweet. (a) Draw a bond-line structure of aspartame. (b) Draw a bond-line structure for each of the three bitter stereoisomers of aspartame.

Bacitracin A is produced by bacteria and therefore contains some residues that are not from the list of 20 naturally occurring amino acids (Figure 25.1). (a) Identify which amino acid residues are found in Table 25.1 and name them. (b) Identify which of these amino acids are d rather than l. (c) Identify all residues that are not listed in Table 25.1.

Draw the structure of the initial PTH derivative formed when the tripeptide Ala-Phe-Val undergoes an Edman degradation.

A peptide with 22 amino acid residues is treated with trypsin to give four fragments, while treatment with chymotrypsin yields six fragments. Identify the sequence of the 22 amino acid residues in the starting peptide. trypsin fragments chymotrypsin fragments Trp-His-Phe-Met-Cys-Arg Pro-Val-Ile-Leu-Arg Lys-Pro-Val-Ile-Leu-Arg-Trp His-Phe Met-Phe-Val-Ala-Tyr-Lys Gly-Pro-Phe-Ala-Val Val-Ala-Tyr Ala-Val Met-Cys-Arg-Gly-Pro-Phe Met-Phe

The tetrapeptide Val-Lys-Ala-Phe is cleaved into two fragments upon treatment with trypsin. Identify the sequence of a tetrapeptide that will produce the same two fragments when treated with chymotrypsin.

Consider the structure of the following cyclic octapeptide. Would cleavage of this peptide with trypsin produce different fragments than cleavage with chymotrypsin? Explain. Phe Phe Phe Phe Arg Arg Arg Arg

Draw all of the steps and reagents necessary to prepare each of the following dipeptides from their corresponding amino acids: (a) Trp-Met (b) Ala-Ile (c) Leu-Val

Draw all of the steps and reagents necessary to prepare a tripeptide with the sequence Ile-Phe-Gly.

Draw all of the steps and reagents necessary to prepare a pentapeptide with the sequence Leu-Val-Phe-Ile-Ala.

Identify all of the steps necessary to prepare each of the following peptides with a Merrifield synthesis: (a) Phe-Leu-Val-Phe (b) Ala-Val-Leu-Ile

Identify the sequence of the tripeptide that would be formed from the following order of reagents. Clearly label the C terminus and N terminus of the tripeptide. Cl POLYMER O O H N 1) Boc 2) CF3COOH 4) CF3COOH 6) CF3COOH 3) Boc OH, DCC O H N 5) Boc OH, DCC O H N 7) HF

Below is the primary structure for a peptide. Identify the regions that are most likely to form b pleated sheets. Trp-His-Pro-Ala-Gly-Gly-Ala-Val-His-Cys-Asp-Ser-Arg-Arg-Ala-Gly-Ala-Phe

Draw a bond-line structure showing the zwitterionic form of each of the following amino acids: (a) l-Valine (b) l-Tryptophan (c) l-Glutamine (d) l-Proline

The 20 naturally occurring amino acids (Table 25.1) are all l amino acids, and they all have the S configuration, with the exception of glycine (which lacks a chirality center) and cysteine. Naturally occurring cysteine is an l amino acid, but it has the R configuration. Explain.

Draw a Fischer projection for each of the following amino acids: (a) l-Threonine (b) l-Serine (c) l-Phenylalanine (d) l-Asparagine

Seventeen of the 20 naturally occurring amino acids (Table 25.1) exhibit exactly one chirality center. Of the remaining three amino acids, glycine has no chirality center, and the other two amino acids each have two chirality centers. (a) Identify the amino acids with two chirality centers. (b) Assign the configuration of each chirality center in these two amino acids.

Draw all stereoisomers of l-isoleucine. In each stereoisomer, assign the configuration (R or S) of all chirality centers.

Arginine is the most basic of the 20 naturally occurring amino acids. At physiological pH, the side chain of arginine is protonated. Identify which nitrogen atom in the side chain is protonated. (Hint: Consider all three possibilities and draw all resonance structures.)

Histidine possesses a basic side chain which is protonated at physiological pH. Identify which nitrogen atom in the side chain is protonated.

Draw the form of l-glutamic acid that predominates at each pH: (a) 1.9 (b) 2.4 (c) 5.8 (d) 10.4

For each of the following amino acids, draw the form that is expected to predominate at physiological pH: (a) l-Isoleucine (b) l-Tryptophan (c) l-Glutamine (d) l-Glutamic acid

Using the data in Table 25.2, calculate the pI of the following amino acids: (a) l-Alanine (b) l-Asparagine (c) l-Histidine (d) l-Glutamic acid

Just as each amino acid has a unique pI value, proteins also have an overall observable pI. For example, lysozyme (present in tears and saliva) has a pI of 11.0 while pepsin (used in our stomachs to digest other proteins) has a pI of 1.0. What information does this give you about the types of amino acid residues that predominantly make up each of these proteins?

For each amino acid, draw the structure that predominates at the isoelectric point: (a) l-Glutamine (b) l-Phenylalanine (c) l-Proline (d) l-Threonine

Optically active amino acids undergo racemization at the a position when treated with strongly basic conditions. Provide a mechanism that supports this observation.

A mixture containing glycine, l-glutamine, and l-asparagine was subjected to electrophoresis. Identify which of the amino acids moved the farthest distance assuming that the experiment was performed at the pH indicated: (a) 6.0 (b) 5.0

Draw the products that are expected when each of the following amino acids is treated with ninhydrin: (a) l-Aspartic acid (b) l-Leucine (c) l-Phenylalanine (d) l-Proline

A mixture of amino acids was treated with ninhydrin, and the following aldehydes were all observed in the product mixture: S H O O H H H O (a) Identify the structure and name all three amino acids in the starting mixture. (b) In addition to the aldehydes, a purple-colored product is obtained. Draw the structure of the compound responsible for the purple color. (c) Describe the origin of the purple color.

Show how you would use a Strecker synthesis to make valine.

Under similar conditions, alanine and valine were each prepared with an amidomalonate synthesis, and alanine was obtained in higher yields than valine. Explain the difference in yields.

The amidomalonate synthesis can be used to prepare amino acids from alkyl halides. When the amidomalonate synthesis is used to make glycine, no alkyl halide is required. Explain.

Predict the major product(s) in each of the following cases: OH O 1) Br2, PBr3 2) H2O 3) Excess NH3 ? (a) 1) NH4Cl, NaCN 2) H3O+ H (b) O ? EtO OEt O O N O H 1) NaOEt 2) CH3I 3) H3O+, heat ? (c)

Show how racemic valine can be prepared by each of the following methods: (a) The Hell-Volhard-Zelinsky reaction (b) The amidomalonate synthesis (c) The Strecker synthesis

How many different pentapeptides can be constructed from the 20 naturally occurring amino acids in Table 25.1?

Using an asymmetric catalytic hydrogenation, identify the starting alkene that you would use to make l-histidine.

Using three-letter abbreviations, identify all possible acyclic tripeptides containing l-leucine, l-methionine, and l-valine.

Draw the predominant form of Asp-Lys-Phe at physiological pH.

Draw a bond-line structure of the peptide that corresponds with the following sequence of amino acid residues and identify the N terminus and C terminus: Trp-Val-Ser-Met-Gly-Glu

Methionine enkephalin is a pentapeptide that is produced by the body to control pain. From the sequence of its amino acid residues, draw a bond-line structure of methionine enkephalin. Tyr Gly Gly Phe Met Methionine enkephalin N terminus C terminus

From its amino acid sequence, draw the form of aspartame that is expected to predominate at physiological pH: Asp-Phe-OCH3

It is believed that penicillin antibiotics are biosynthesized from amino acid precursors. Identify the two amino acids that are most likely utilized during the biosynthesis of penicillin antibiotics: N O N S COOH

Green fluorescent protein (GFP), first isolated from bioluminescent jellyfish, is a protein containing 238 amino acid residues. The discovery of GFP has revolutionized the field of fluorescence microscopy, which enables biochemists to monitor the biosynthesis of proteins. The 2008 Nobel Prize in Chemistry was awarded to Martin Chalfie, Osamu Shimomura, and Roger Tsien for the discovery and development of GFP. The structural subunit of GFP responsible for fluorescence, called the fluorophore, results when three amino acid residues undergo cyclization. Identify the three amino acids that are necessary for the biosynthesis of this fluorophore: N HO N N O H H HO O

Propose two structures for a tripeptide that contains glycine, l-alanine, and l-phenylalanine but does not react with phenyl isothiocyanate.

Bradykinin has the following sequence: (N terminus) Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg (C terminus) Identify all fragments that will be produced when bradykinin is treated with: (a) Trypsin (b) Chymotrypsin

Identify the N-terminal residue of a peptide that yields the following PTH derivative upon Edman degradation: HN N O S

Treatment of a tripeptide with phenyl isothiocyanate yields compound A and a dipeptide. Treatment of the dipeptide with phenyl isothiocyanate yields compound B and glycine. Identify the structure of the starting tripeptide. HN N O S Compound A HN N O S Compound B

Glucagon is a peptide hormone produced by the pancreas that, with insulin, regulates blood glucose levels. Glucagon is comprised of 29 amino acid residues. Treatment with trypsin yields four fragments, while treatment with chymotrypsin yields six fragments. Identify the sequence of amino acid residues for glucagon and determine whether any disulfide bridges are present. Trypsin fragments His-Ser-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Lys Ala-Gln-Asp-Phe-Val-Gln-Trp-Leu-Met-Asn-Thr Tyr-Leu-Asp-Ser-Arg Arg Chymotrypsin fragments His-Ser-Gln-Gly-Thr-Phe Thr-Ser-Asp-Tyr Leu-Met-Asn-Thr Ser-Lys-Tyr Leu-Asp-Ser-Arg-Arg-Ala-Gln-Asp-Phe Val-Gln-Trp

When the N terminus of a peptide is acetylated, the peptide derivative that is formed is unreactive toward phenyl isothiocyanate. Explain. N H H PEPTIDE Acetylation N H PEPTIDE

Predict the major product(s) of the reaction between l-valine and: (a) MeOH, H+ (b) Di-tert-butyl-dicarbonate (c) NaOH, H2O (d) HCl

Show all steps necessary to make the dipeptide Phe-Ala from l-phenylalanine and l-alanine.

Draw all four possible dipeptides that are obtained when a mixture of l-phenylalanine and l-alanine is treated with DCC.

Identify the steps you would use to combine Val-Leu and PheIle to form the tetrapeptide Phe-Ile-Val-Leu.

Identify all of the steps necessary to prepare the tripeptide LeuVal-Ala with a Merrifield synthesis.

Draw the structure of the protected amino acid that must be anchored to the solid support in order to use a Merrifield synthesis to prepare leucine enkephalin. (N terminus) Try-Gly-Gly-Phe-Leu (C terminus)

A proline residue will often appear at the end of an a helix but will rarely appear in the middle. Explain why proline generally cannot be incorporated into an a helix.

Draw a mechanism for the following reaction: OH O H2N OH O H O N O O O O O O

Draw the alkyl halide that would be necessary to make the amino acid tyrosine using an amidomalonate synthesis. This alkyl halide is highly susceptible to polymerization. Draw the structure of the expected polymeric material.

When leucine is prepared with an amidomalonate synthesis, isobutylene (also called 2-methylpropene) is a gaseous by-product. Draw a mechanism for the formation of this by-product.

The side chain of tryptophan is not considered to be basic, despite the fact that it possesses a nitrogen atom with a lone pair. Explain.

Consider a process that attempts to prepare tyrosine using a Hell-Volhard-Zelinsky reaction: (a) Identify the necessary starting carboxylic acid. (b) When treated with Br2, the starting carboxylic acid can react with two equivalents to produce a compound with molecular formula C9H8Br2O3, in which neither of the bromine atoms is located at the a position. Identify the likely structure of this product.

Proton NMR spectroscopy provides evidence for the restricted rotation of a peptide bond. For example, N,N-dimethylformamide exhibits three signals in its proton NMR spectrum at room temperature. Two of those signals are observed upfield, at 2.9 and 3.0 ppm. As the temperature is raised, the two signals begin to merge together. Over 180C, these two signals combine into one signal. Explain how these results are evidence for the restricted rotation of peptide bonds.

We saw in Section 25.6 that DCC can be used to form a peptide bond. We explored the mechanism, and we saw that DCC activates the COOH group so that it readily undergoes nucleophilic acyl substitution. An alternative method for activating a COOH group involves converting it into an activated ester, such as a para-nitrophenyl ester: OH O R Boc O O R NO2 Boc A para-nitrophenyl ester H N H N The activated ester is readily attacked by a suitably protected amino acid to form a peptide bond: N H O Boc R R OR O O O H2N R R O O H N H N R NO2 Boc + (a) Explain how the p-nitrophenyl ester activates the carbonyl group toward nucleophilic acyl substitution. (b) What is the function of the nitro group? (c) A meta-nitrophenyl ester is less activating than a para-nitrophenyl ester. Explain.

When the following compound is treated with concentrated HCl at 100C for several hours, hydrolysis occurs, producing one of the 20 naturally occurring amino acids. Identify which one. O H2N O