1. Chapter 22
The Organic Chemistry of Amino Acids, Peptides, and Proteins
Paula Yurkanis Bruice
University of California,
Santa Barbara

2. Amino Acids and Peptides
Peptides and proteins are polymers of amino acids linked together by amide bonds.

3. Proteins Have Diverse Functions

7. Lysine and Arginine The amino group is on the epsilon carbon.
The guanidino group is on the delta carbon.

8. Histidine and Tryptophan
Histidine is an imidazole-substituted alanine.
Tryptophan is an indole-substituted alanine.

9. D-Sugars and L-Amino Acids

10. An Antibiotic

11. Ornithine Has One Less Methylene Group Than Lysine

12. The Structure of an Amino Acid
An amino acid can never exist as an uncharged compound.

14. Some amino acids have ionizable hydrogens on their side chains.
Histidine
Some amino acids have ionizable hydrogens on their side chains.

15. The pI of Alanine
The isoelectric point (pI) of an amino acid is the pH at which it has no net charge.

16. The pI of Lysine

17. The pI of Glutamic Acid

18. Electrophoresis
Electrophoresis separates amino acids on the basis of their pI values.
Ninhydrin is used to detect the individual amino acids.

19. Ninhydrin

20. Chromatography separates amino acids on the basis of their polarity.

21. A Cation-Exchange Resin
The resin exchanges the Na+ counterions for positively charged groups.

22. Separation of Three Amino Acids

23. A Chromatogram
a chromatogram obtained from separation of amino acids using an automated amino acid analyzer

24. Synthesizing an Amino Acid Using an HVZ Reaction

25. Synthesizing an Amino Acid by Reductive Animation

26. Synthesizing an Amino Acid Using the N-Phthalimidomalonic Ester Synthesis

27. Synthesizing an Amino Acid Using a Strecker Synthesis

28. Resolution of a Racemic Mixture of Amino Acids

29. A Tripeptide

30. Commas Indicate the Sequence is Not Known; Hyphens Indicate the Sequence is Known
Val is the N-terminal amino acid.
His is the C-terminal amino acid.

31. A Peptide Bond Has 40% Double Bond Character

32. The squares indicate the plane of each peptide bond.
A Polypeptide Chain
The squares indicate the plane of each peptide bond.

33. Mild Oxidation of a Thiol

34. The Mechanism

35. Reduction of a Disulfide

36. Oxidation of Cysteine Forms Cystine

37. Disulfide bridges contribute to the overall shape of the protein.

38. Straight and Curly Hair

39. Insulin Insulin has two interchain disulfide bridges and
one intrachain disulfide bridge.

40. peptides synthesized by the body to control pain
Enkephalins
peptides synthesized by the body to control pain

41. Peptide Hormones Bradykinin inhibits inflammation of tissues.
Vasopressin regulates the bond’s retention of water;
it is released in response to stress.
Oxytocin induces labor and stimulates milk production.

42. NutraSweet
NutraSweet is the methyl ester of a dipeptide of aspartate and phenylalanine

43. Because amino acids have two functional groups,
Synthesizing Gly-Ala
Because amino acids have two functional groups,
mixing Gly and Ala (and heating) would lead to four different dipeptides.

44. Strategy for Peptide Bond Synthesis
To make a peptide bond, the N-terminal amino acid needs to have its amino group protected and its carboxyl group activated.

45. Protecting the Amino Group

46. Activating the Carboxyl Group

47. Forming a New Peptide Bond

48. Adding a Third Amino Acid

49. Removing the Protecting Group
When the desired number of amino acids has been added to the chain, the protecting group can be removed.

50. Assuming an 80% Yield for Formation of Each Peptide Bond

51. Automated Solid-Phase Peptide Synthesis
The N-protected C-terminal amino acid is added to the resin.

52. Automated Solid-Phase Peptide Synthesis
The protecting group is removed.
The next amino acid with its amino group protected and then its carboxyl group activated is added to the resin.

53. Automated Solid-Phase Peptide Synthesis
The protecting group is removed.
The next amino acid with its amino group protected and then its carboxyl group activated is added to the resin.

54. Removing the Protecting Group
The protecting group is removed.
The peptide is removed from the resin.

55. Protein Structure
Primary structure: the sequence of amino acids and the location of disulfide bonds
Secondary structure: the conformations assumed by the protein’s backbone
when it folds
Tertiary structure: the three-dimensional structure of the entire protein
Quaternary structure: the way the individual peptide chains are arranged

56. Reducing the Disulfide Bridges in Proteins
The first step in determining the sequence of amino acids is cleaving the disulfide bridges.

57. Acid-Catalyzed Hydrolysis of the Peptide Bonds
The next step is to determine the number and kinds of amino acids in the peptide or protein by hydrolysis of all the amide bonds and then analysis of the mixture.

58. Identifying the N-Terminal Amino Acid

59. The Thiazoline Rearranges to a PTH-Amino Acid
For the mechanism, see Problem 72.
The particular PTH–amino acid can be identified by chromatography using known standards.

60. Carboxypeptidase is Used to Determine the C-Terminal Amino Acid
Carboxypeptidase catalyzes the hydrolysis of the C-terminal peptide bond.
Carboxypeptidase is an exopeptidase.
Carboxypeptidase A cleaves off the C-terminal amino acid as long as it is not Arg or Lys.
Carboxypeptidase B cleaves off the C-terminal amino acid only if it is Arg or Lys.

61. Trypsin is an Endopeptidase
Trypsin cleaves on the right of amino acids with positively charged side chains (Arg and Lys).

62. Cleavage by Trypsin

63. Chymotrypsin is an Endopeptidase
Chymotrypsin cleaves on the right of amino acids that contain amino acids with aromatic six-membered rings (Phe, Tyr, and Trp).

64. Elastase cleaves on the right of small amino acids (Gly and Ala).
Elastase is an Endopeptidase
Elastase cleaves on the right of small amino acids (Gly and Ala).

65. An Enzyme Will Not Hydrolyze a Peptide Bond if Proline is at the Cleavage Site

66. Cyanogen Bromide Cleaves on the Right Side of Methionine

67. The Mechanism

68. Three factors determine the secondary structure:
The regional planarity about each peptide bond limits the conformations of the peptide chain.
The number of peptide groups that engage in hydrogen bonding is maximized.
The need for adequate separation between nearby R groups

69. Hydrogen Bonding Between Peptide Groups
Proteins fold to maximize the number of hydrogen bonds between peptide groups.

70. The α-helix is stabilized by hydrogen bonds.

71. β-Pleated Sheets

72. The Secondary Structure of a Protein

73. The Tertiary Structure of a Protein

74. Stabilizing Interactions

75. The Quaternary Structure of Hemoglobin
The individual chains are called subunits.