Arginine, the most basic of the 20 common amino acids, contains a guanidino functional

How many of the a-amino acids shown in Table 26-1 contain aromatic rings? How many contain sulfur? How many contain alcohols? How many contain hydrocarbon side chains?

Of the 19 L amino acids, 18 have the S configuration at the \(\alpha\) carbon. Cysteine is the only L amino acid that has an R configuration. Explain. Equation Transcription: Text Transcription: \alpha

The amino acid threonine, (2S,3R)-2-amino-3-hydroxybutanoic acid, has two chirality centers. (a) Draw threonine, using normal, wedged, and dashed lines to show dimensionality. (b) Draw a diastereomer of threonine, and label its chirality centers as R or S.

Hemoglobin has pI 5 6.8. Does hemoglobin have a net negative charge or net positive charge at pH 5 5.3? At pH 5 7.3?

Show how you could prepare the following \(\alpha-\text { amino }\) acids from the appropriate carboxylic acids: (a) Phenylalanine (b) Valine Equation Transcription: Text Transcription: \alpha- amino

What alkyl halides would you use to prepare the following \(\alpha-\text { amino }\) acids by the amidomalonate method? (a) Leucine (b) Histidine (c) Tryptophan (d) Methionine Equation Transcription: Text Transcription: \alpha- amino

Show how you could prepare the following amino acid enantioselectively:

There are six isomeric tripeptides that contain valine, tyrosine, and glycine. Name them using both three- and one-letter abbreviations.

Draw the structure of M-P-V-G, and indicate its amide bonds.

Show the structure of the product you would expect to obtain by \(S_{N} 2\) reaction of a cysteine residue with iodoacetic acid. Equation Transcription: Text Transcription: S_{N} 2

Show the structures of the products obtained on reaction of valine with ninhydrin.

The octapeptide angiotensin II has the sequence Asp-Arg-Val-Tyr-Ile-His-ProPhe. What fragments would result if angiotensin II were cleaved with trypsin? With chymotrypsin?

What is the N-terminal residue on a peptide that gives the following PTH derivative upon Edman degradation?

Draw the structure of the PTH derivative that would be formed by Edman degradation of angiotensin II (Problem 26-12).

Give the amino acid sequence of hexapeptides that produce the following sets of fragments upon partial acid hydrolysis: (a) Arg, Gly, Ile, Leu, Pro, Val gives Pro-Leu-Gly, Arg-Pro, Gly-Ile-Val (b) N, L, M, W, V2 gives V-L, V-M-W, W-N-V

Show the mechanism for formation of a Boc derivative by reaction of an amino acid with di-tert-butyl dicarbonate.

Write all five steps required for the synthesis of Leu-Ala from alanine and leucine.

To what classes do the following enzymes belong? (a) Pyruvate decarboxylase (b) Chymotrypsin (c) Alcohol dehydrogenase

Identify the following amino acids:

Give the sequence of the following tetrapeptide (yellow 5 S):

Isoleucine and threonine are the only two amino acids with two chirality centers. Assign R or S coniguration to the methyl-bearing carbon atom of isoleucine.

Is the following structure a D amino acid or an L amino acid? Identify it.

Give the sequence of the following tetrapeptide:

The reaction of ninhydrin with an a-amino acid occurs in several steps. (a) The first step is formation of an imine by reaction of the amino acid with ninhydrin. Show its structure and the mechanism of its formation. (b) The second step is a decarboxylation. Show the structure of the product and the mechanism of the decarboxylation reaction. (c) The third step is hydrolysis of an imine to yield an amine and an aldehyde. Show the structures of both products and the mechanism of the hydrolysis reaction. (d) The final step is formation of the purple onion. Show the mechanism of the reaction. Equation Transcription: Text Transcription: H_2NNCHCO_2H RCHO+CO_2

The chloromethylated polystyrene resin used for Merriield solidphase peptide synthesis is prepared by treatment of polystyrene with chloromethyl methyl ether and a Lewis acid catalyst. Propose a mechanism for the reaction. Equation Transcription: Text Transcription: CH_2-CH CH_3OCH_2Cl SnCl_4 CH_2-CH CH_2Cl

An Fmoc protecting group can be removed from an amino acid by treatment with the amine base piperidine. Propose a mechanism. Equation Transcription: Text Transcription: pK_a=23 C-NHCHCO H_2O CO_2=H_3NCHCO-R

Proteins can be cleaved speciically at the amide bond on the carboxyl side of methionine residues by reaction with cyanogen bromide, \(\mathrm{BrC} \equiv \mathrm{N}\). The reaction occurs in several steps: (a) The first step is a nucleophilic substitution reaction of the sulfur on the methionine side chain with BrCN to give a cyanosulfonium ion, \({\left[\mathrm{R}_{2}\mathrm{SCN}\right]^{+}}\). Show the structure of the product, and propose a mechanism for the reaction. (b) The second step is an internal \(\mathrm{S}_{\mathrm{N}} 2\) reaction, with the carbonyl oxygen of the methionine residue displacing the positively charged sulfur leaving group and forming a five-membered ring product. Show the structure of the product and the mechanism of its formation. (c) The third step is a hydrolysis reaction to split the peptide chain. The carboxyl group of the former methionine residue is now part of a lactone (cyclic ester) ring. Show the structure of the lactone product and the mechanism of its formation. (d) The inal step is a hydrolysis of the lactone to give the product shown. Show the mechanism of the reaction. Equation Transcription: Text Transcription: BrC \equiv N NHCHCNHCH-C-NHCHC CH_2 CH_2-S-CH_3 BrCN H_2O NHCHCNHCH-C-OH+H_2NCHC-R CH_2 CH_2-OH [R_2SCN]+ S_N2

A clever new method of peptide synthesis involves formation of an amide bond by reaction of an \(\alpha-\text { keto }\) acid with an N-alkylhydroxylamine: The reaction is thought to occur by nucleophilic addition of the N-alkyl hydroxylamine to the keto acid as if forming an oxime (Section 19-8), followed by decarboxylation and elimination of water. Show the mechanism. Equation Transcription: Text Transcription: \alpha-keto CO2- R'+CO2+H2O \alpha-keto

Except for cysteine, only S amino acids occur in proteins. Several R amino acids are also found in nature, however. (R)-Serine is found in earthworms, and (R)-alanine is found in insect larvae. Draw Fischer projections of (R)-serine and (R)-alanine. Are these D or L amino acids?

Cysteine is the only amino acid that has L stereochemistry but an R configuration. Make up a structure for another L amino acid of your own creation that also has an R configuration.

Draw a Fischer projection of (S)-proline.

Show the structures of the following amino acids in their zwitterionic forms: (a) Trp (b) Ile (c) Cys (d) His

Proline has \(p K_{a 1}=51.99\) and \(p K_{a 2}=10.60\). Use the Henderson– Hasselbalch equation to calculate the ratio of protonated and neutral forms at pH = 2.50. Calculate the ratio of neutral and deprotonated forms at pH = 9.70. Equation Transcription: Text Transcription: pK_a1=5 1.99 pK_a2=10.60

Using both three- and one-letter codes for amino acids, write the structures of all possible peptides containing the following amino acids: (a) Val, Ser, Leu (b) Ser, Leu2, Pro

Look at the side chains of the 20 amino acids in Table 26-1, and then think about what is not present. None of the 20 contain either an aldehyde or a ketone carbonyl group, for instance. Is this just one of nature’s oversights, or is there a likely chemical reason? What complications might an aldehyde or ketone carbonyl group cause?

Show how you could use the acetamidomalonate method to prepare the following amino acids: (a) Leucine (b) Tryptophan

Show how you could prepare the following amino acids using a reductive amination: (a) Methionine (b) Isoleucine

Show how you could prepare the following amino acids enantioselectively: (a) Pro (b) Val

Serine can be synthesized by a simple variation of the amidomalonate method using formaldehyde rather than an alkyl halide. How might this be done?

Predict the product of the reaction of valine with the following reagents: (a) \(\mathrm{CH}_{3} \mathrm{CH}_{2} \mathrm{OH}\), acid (b) Di-tert-butyl dicarbonate (c) \(\mathrm{KOH}, \mathrm{H}_{2} \mathrm{O}\) (d) \(\mathrm{CH}_{3} \mathrm{COCl}\), pyridine; then \(\mathrm{H}_{2} \mathrm{O}\) Equation Transcription: Text Transcription: CH_3CH_2OH KOH, H_2O CH_3COCl H_2O

Draw resonance forms for the purple anion obtained by reaction of ninhydrin with an \(\alpha-\text { amino }\) acid (Problem 26-24). Equation Transcription: Text Transcription: \alpha- amino

Write full structures for the following peptides: (a) C-H-E-M (b) P-E-P-T-I-D-E

Propose two structures for a tripeptide that gives Leu, Ala, and Phe on hydrolysis but does not react with phenyl isothiocyanate.

Show the steps involved in a synthesis of Phe-Ala-Val using the Merrifield procedure.

Draw the structure of the PTH derivative product you would obtain by Edman degradation of the following peptides: (a) I-L-P-F (b) D-T-S-G-A

Which amide bonds in the following polypeptide are cleaved by trypsin? By chymotrypsin? Phe-Leu-Met-Lys-Tyr-Asp-Gly-Gly-Arg-Val-Ile-Pro-Tyr

What kinds of reactions do the following classes of enzymes catalyze? (a) Hydrolases (b) Lyases (c) Transferases

Which of the following amino acids are more likely to be found on the exterior of a globular protein, and which on the interior? Explain. (a) Valine (b) Aspartic acid (c) Phenylalanine (d) Lysine

Leuprolide is a synthetic nonapeptide used to treat both endometriosis in women and prostate cancer in men. (a) Both C-terminal and N-terminal amino acids in leuprolide have been structurally modified. Identify the modifications. (b) One of the nine amino acids in leuprolide has D stereochemistry rather than the usual L. Which one? (c) Write the structure of leuprolide using both one- and three-letter abbreviations. (d) What charge would you expect leuprolide to have at neutral pH? Equation Transcription: Text Transcription: NHCH_2CH_3 NH_2

The a-helical parts of myoglobin and other proteins stop whenever a proline residue is encountered in the chain. Why is proline never present in a protein a helix?

Arginine, the most basic of the 20 common amino acids, contains a guanidino functional group in its side chain. Explain, using resonance structures to show how the protonated guanidino group is stabilized. Guanidino group Arginine CO2 N H H NH3 NH + H2N C

Cytochrome c is an enzyme found in the cells of all aerobic organisms. Elemental analysis of cytochrome c shows that it contains 0.43% iron. What is the minimum molecular weight of this enzyme?

Evidence for restricted rotation around amide CO]N bonds comes from NMR studies. At room temperature, the 1H NMR spectrum of N,Ndimethylformamide shows three peaks: 2.9 d (singlet, 3 H), 3.0 d (singlet, 3 H), and 8.0 d (singlet, 1 H). As the temperature is raised, however, the two singlets at 2.9 d and 3.0 d slowly merge. At 180 C, the 1H NMR spectrum shows only two peaks: 2.95 d (singlet, 6 H) and 8.0 d (singlet, 1 H). Explain this temperature-dependent behavior. N,N-Dimethylformamide H O C CH3 N H3C

Propose a structure for an octapeptide that shows the composition Asp, Gly2, Leu, Phe, Pro2, Val on amino acid analysis. Edman analysis shows a glycine N-terminal group, and leucine is the C-terminal group. Acidic hydrolysis gives the following fragments: Val-Pro-Leu, Gly, Gly-Asp-Phe-Pro, Phe-Pro-Val

Look up the structure of human insulin (page 883), and indicate where in each chain the molecule is cleaved by trypsin and chymotrypsin.

What is the structure of a nonapeptide that gives the following fragments when cleaved? Trypsin cleavage: Val-Val-Pro-Tyr-Leu-Arg, Ser-Ile-Arg Chymotrypsin cleavage: Leu-Arg, Ser-Ile-Arg-Val-Val-Pro-Tyr

Oxytocin, a nonapeptide hormone secreted by the pituitary gland, functions by stimulating uterine contraction and lactation during childbirth. Its sequence was determined from the following evidence: 1. Oxytocin is a cyclic compound containing a disulfide bridge between two cysteine residues. 2. When the disulfide bridge is reduced, oxytocin has the constitution Asn, Cys2, Gln, Gly, Ile, Leu, Pro, Tyr. 3. Partial hydrolysis of reduced oxytocin yields seven fragments: Asp-Cys, Ile-Glu, Cys-Tyr, Leu-Gly, Tyr-Ile-Glu, Glu-Asp-Cys, and Cys-Pro-Leu. 4. Gly is the C-terminal group. 5. Both Glu and Asp are present as their side-chain amides (Gln and Asn) rather than as free side-chain acids. What is the amino acid sequence of reduced oxytocin? What is the structure of oxytocin itself?

Aspartame, a nonnutritive sweetener marketed under such trade names as Equal, NutraSweet, and Canderel, is the methyl ester of a simple dipeptide, Asp-Phe-OCH3. (a) Draw the structure of aspartame. (b) The isoelectric point of aspartame is 5.9. Draw the principal structure present in aqueous solution at this pH. (c) Draw the principal form of aspartame present at physiological pH 5 7.3.

Refer to Figure 26-4 on page 887 and propose a mechanism for the final step in Edman degradationthe acid-catalyzed rearrangement of the ATZ derivative to the PTH derivative.

Amino acids are metabolized by a transamination reaction in which the ]NH2 group of the amino acid changes places with the keto group of an a-keto acid. The products are a new amino acid and a new a-keto acid. Show the product from transamination of isoleucine.

The first step in the biological degradation of histidine is formation of a 4-methylidene-5-imidazolone (MIO) by cyclization of a segment of the peptide chain in the histidine ammonia lyase enzyme. Propose a mechanism. 4-Methylidene-5-imidazolone (MIO) CH3 NH NH Enz H Enz O O O H CH2OH H N CH2 O Enz O CH3 NH Enz H N N

The first step in the biological degradation of lysine is reductive amination with a-ketoglutarate to give saccharopine. Nicotinamide adenine dinucleotide phosphate (NADPH), a relative of NADH, is the reducing agent. Show the mechanism. Saccharopine O2C C N O2 H H NH3 + Lysine O2C H H2N CO2 H NH3 + -Ketoglutarate + CO2 O 2C O NADPH/H+ NADP+