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

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?

1. Ala, Trp

2. Val, Pro, Asp

3. Pro, Val

4. Ala, Glu

5. Trp, Ala, Arg

6. Arg, Gly

7. Glu, Ala, Leu

8. Met, Pro, Leu, Glu

Indicate the peptides produced 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

Three peptides were obtained from a trypsin digestion of two different polypeptides. In each case, indicate the possible sequences from the given data and tell what further experiment should be carried out in order to determine the primary structure of the polypeptide.

a. polypeptide I:

1. Val-Gly-Asp-Lys

2. Leu-Glu-Pro-Ala-Arg

3. Ala-Leu-Gly-Asp

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

Glycine has pK_a values of 2.34 and 9.60. At what pH does glycine exist in the forms shown?

a.

Show the peptides that would result from cleavage by the indicated reagent: 

a. Val-Arg-Gly-Met-Arg-Ala-Ser by carboxypeptidase A

b. Ser-Phe-Lys-Met-Pro-Ser-Ala-Asp by cyanogen bromide

c. Arg-Ser-Pro-Lys-Lys-Ser-Glu-Gly by trypsin

Which has a higher percentage of negative charge at physiological pH (7.4), leucine with pI = 5.98 or asparagine with pI = 5.43?

Draw the form of aspartate that predominates at the following pH values: c. pH=6.0

Draw the form of aspartate that predominates at the following pH values:

d. pH=11.0

What aldehydes are formed when the following amino acids are treated with ninhydrin? 

b. leucine 

c. arginine

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

Explain the difference in the pK_a values of the carboxyl groups of alanine, serine, and cysteine

Identify the location and type of charge on the hexapeptide Lys-Ser-Asp-Cys-His-Tyr at each of the following pH values:

c. pH=7

Identify the location and type of charge on the hexapeptide Lys-Ser-Asp-Cys-His-Tyr at each of the following pH values:

d. pH=12

Draw the product obtained when a lysine side chain in a polypeptide reacts with maleic anhydride.

After the polypeptide shown below was treated with maleic anhydride, it was hydrolyzed by trypsin. (After a polypeptide is treated with maleic anhy- dride, trypsin will cleave the polypeptide only on the C-side of arginine.)

Gly-Ala-Asp-Ala-Leu-Pro-Gly-Ile-Leu-Val-Arg-Asp-Val-Gly-Lys-Val-Glu-Val-Phe-Glu-Ala-Gly- Arg-Ala-Glu-Phe-Lys-Glu-Pro-Arg-Leu-Val-Met-Lys-Val-Glu-Gly-Arg-Pro-Val-Gly-Ala-Gly-Leu-Trp

a. After a polypeptide is treated with maleic anhydride, why does trypsin no longer cleave it on the C-side of lysine?

b. How many fragments are obtained from the polypeptide?

α-Amino acids can be prepared by treating an aldehyde with ammonia/trace acid, followed by hydrogen cyanide, followed by acid-catalyzed hydrolysis.

a. Draw the structures of the two intermediates formed in this reaction.

α-Amino acids can be prepared by treating an aldehyde with ammonia/trace acid, followed by hydrogen cyanide, followed by acid-catalyzed hydrolysis.

b. What amino acid is formed when the aldehyde that is used is 3-methylbutanal?

c. What aldehyde is needed to prepare isoleucine?

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?

1. Ser, Lys, Trp

2. Gly, His, Ala

3. Glu, Val, Ser

4. Leu, Glu, Ser

5. Met, Ala, Gly

6. Ser, Lys, Val

7. Glu, His

8. Leu, Lys, Trp

9. Lys, Ser

10. Glu, His, Val

11. Trp, Leu, Glu

12. Ala, Met

Glycine has pK_a values of 2.3 and 9.6. Do you expect the pK_a values of glycylglycine to be higher or lower than these values?

Write the mechanism for the reaction of an amino acid with di-tert-butyl dicarbonate.

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.

Show how valine can be prepared by

a. a Hell–Volhard–Zelinski reaction.

Show how valine can be prepared by

c. a reductive amination.

Show how valine can be prepared by

d. a N-phthalimidomalonic ester synthesis. 

Propose a mechanism for the rearrangement of the thiazoline obtained from the reaction of Edman's reagent with a peptide to a PTH-amino acid. (Hint: Thioesters are very reactive toward nucleophiles.)