Introduction to Organic Chemistry 2 ed William H. Brown

1. Introduction to Organic Chemistry2 edWilliam H. Brown

2. Chapter 18 Amino Acids & Proteins

3. Amino Acids • Amino acid: a compound that contains both an amino group and a carboxyl group • a-Amino acid: an amino acid in which the amino group is on the carbon adjacent to the carboxyl group • although a-amino acids are commonly written in the unionized form, they are more properly written in the zwitterion (internal salt) form

4. Chirality of Amino Acids • With the exception of glycine, all protein-derived amino acids have at least one stereocenter (the a-carbon) and are chiral • the vast majority of a-amino acids have the L-configuration at the a -carbon

5. 20 Protein-Derived AA

6. 20 Protein-Derived AA

7. 20 Protein-Derived AA

8. 20 Protein-Derived AA

9. 20 Protein-Derived AA • Structural features • all 20 are a-amino acids • for 19 of the 20, the a-amino group is primary; for proline it is secondary • with the exception of glycine, the a-carbon of each is a stereocenter • isoleucine and threonine contain a second stereocenter • the sulfhydryl group of cysteine, the imidazole group of histidine, and the phenolic hydroxyl of phenylalanine are partially ionized at pH 7.0, but the ionic form is not the major form at this pH

10. Acid- Base Proper- ties

11. Acid-Base Properties

12. Acidity: a-CO2H Groups • The average pKa of an a-carboxyl group is 2.19, which makes it a considerably stronger acid than acetic acid (pKa 4.76) • the greater acid strength is due to the electron-withdrawing inductive effect of the -NH3+ group

13. Acidity: side chain -CO2H • Side chain -CO2H groups are stronger acids than acetic acid • the greater acid strength is due to the electron-withdrawing inductive effect of the a-NH3+ group, • the effect decreases with distance from the a-NH3+ group

14. Acidity: a-NH3+ groups • The average value of pKa for an a-NH3+ group is 9.47, compared with an average value of 10.60 for a 1° alkylammonium ion

15. Basicity-Guanidine Group • The side chain of arginine is a considerably stronger base than an aliphatic amine • its basicity is due to the large resonance stabilization of the protonated form relative to the neutral form

16. Basicity- Imidazole Group • The imidazole group on the side chain of histidine is a heterocyclic aromatic amine

17. Isoelectric Point • Isoelectric point, pI: the pH at which the majority of amino acid molecules in solution have no net charge • the pI for glycine, for example, falls between the pKa values for the carboxyl and amino groups • given in the following tables are isoelectric points for the 20 protein-derived amino acids

20. Electrophoresis • Electrophoresis: the process of separating compounds on the basis of their electric charge • electrophoresis of amino acids can be carried out using paper, starch, agar, certain plastics, and cellulose acetate as solid supports • In paper electrophoresis • a paper strip saturated with an aqueous buffer of predetermined pH serves as a bridge between two electrode vessels

21. Electrophoresis • a sample of amino acids is applied as a spot on the paper strip • an electric potential is applied to the electrode vessels and amino acids migrate toward the electrode with charge opposite their own • molecules with a high charge density move faster than those with low charge density • molecules at their isoelectric point remain at the origin • after separation is complete, the strip is dried and developed to make the separated amino acids visible

22. Electrophoresis • a reagent commonly used to detect amino acid is ninhydrin

23. Polypeptides & Proteins • In 1902, Emil Fischer proposed that proteins are long chains of amino acids joined by amide bonds to which he gave the name peptide bonds • Peptide bond: the special name given to the amide bond between the a-carboxyl group of one amino acid and the a-amino group of another

24. Serylalanine (Ser-Ala)

25. Peptides • peptide: the name given to a short polymer of amino acids joined by peptide bonds; they are classified by the number of amino acids in the chain • dipeptide: a molecule containing two amino acids joined by a peptide bond • tripeptide: a molecule containing three amino acids joined by peptide bonds • polypeptide: a macromolecule containing many amino acids joined by peptide bonds • protein: a biological macromolecule of molecular weight 5000 g/mol of greater, consisting of one or more polypeptide chains

26. Writing Peptides • by convention, peptides are written from the left, beginning with the free -NH3+ group and ending at the right with the free -CO2- group

27. Ser-Phe-Asp

28. Primary Structure • Primary structure: the sequence of amino acids in a polypeptide chain, read from the N-terminal amino acid to the C-terminal amino acid • Amino acid analysis • hydrolysis of the polypeptide, most commonly carried out using 6 M HCl at elevated temperature • quantitative analysis of the hydrolysate by ion-exchange chromatography

29. Cyanogen Bromide • Cyanogen bromide, BrCN, is specific for cleavage of peptide bonds formed by the carboxyl group of methionine

30. Cyanogen Bromide

31. Enzyme Catalysis • A group of protein-cleaving enzymes can be used to catalyze the hydrolysis of specific peptide bonds. Among them are:

32. Edman Degradation • Edman degradation: cleaves the N-terminal amino acid of a polypeptide chain

33. Primary Structure • Example 18.6 Deduce the 1° structure of this pentapeptide

34. Peptide Bond Geometry • The four atoms of a peptide bond and the two alpha carbons bonded to it lie in a plane with bond angles of approximately 120° about C and N

35. Peptide Bond Geometry • to account for this geometry, Linus Pauling proposed that a peptide bond is most accurately represented as a hybrid of two contributing structures • the hybrid has considerable C-N double bond character and rotation about a peptide bond is restricted

36. Peptide Bond Geometry • two conformations are possible for a planar peptide bond • virtually all peptide bonds in naturally occurring proteins studied to date have the s-trans conformation

37. Secondary Structure • Secondary structure: the ordered arrangements (conformations) of amino acids in localized regions of a polypeptide or protein • To determine from model building which conformations would be of greatest stability, Pauling and Corey assumed that • all six atoms of each peptide bond lie in the same plane and in the s-trans conformation • there is hydrogen bonding between the N-H group of one peptide bond and a C=O group of another peptide bond as shown in the next screen

38. Secondary Structure

39. Secondary Structure • On the basis of model building, Pauling and Corey proposed that two types of secondary structure should be particularly stable • the a-helix • the antiparallel b-pleated sheet • a-Helix: a type of secondary structure in which a section of polypeptide chain coils into a spiral, most commonly a right-handed spiral

40. The a-Helix • polyalanine, cylindrical bonds model, viewed along its length

41. The a-Helix • polyalanine, cylindrical bonds model, viewed from one end

42. The a-Helix • polyalanine, space filling model, viewed along its length

43. The a-Helix • polyalanine, space filling model, viewed from one end

44. The a-Helix • Structural features of the a-helix • there are 3.6 amino acids per turn of the helix • each peptide bond is s-trans and planar • N-H groups of all peptide bonds point in the same direction, which is roughly parallel to the axis of the helix • C=O groups of all peptide bonds point in the opposite direction, and also parallel to the axis of the helix • the C=O group of each peptide bond is hydrogen bonded to the N-H group of the peptide bond four amino acid units away from it • all R- groups point outward from the helix

45. b-Pleated Sheet • The antiparallel b-pleated sheet consists of adjacent polypeptide chains running in opposite directions • each peptide bond is planar and has the s-trans conformation • the C=O and N-H groups of peptide bonds from adjacent chains point toward each other and are in the same plane so that hydrogen bonding is possible between them • all R- groups on any one chain alternate, first above, then below the plane of the sheet, etc.

46. b-Pleated Sheet • polyalanine

47. Tertiary Structure • Tertiary structure: the three-dimensional arrangement in space of all atoms in a single polypeptide chain • disulfide bonds between the side chains of cysteine play an important role in maintaining 3° structure

48. Quaternary Structure • Quaternary structure: the arrangement of polypeptide chains into a noncovalently bonded aggregation • the major factor stabilizing the aggregation of polypeptide subunits is the hydrophobic effect • Hydrophobic effect: the tendency of nonpolar groups to cluster together in such a way as to be shielded from contact with an aqueous environment

49. Quaternary Structure • if two polypeptide chains, for example, each have one hydrophobic patch, each patch can be shielded from contact with water if the chains form a dimer

50. Amino Acids & Proteins End of Chapter 18