1. Amino Acids and Peptides Precursors of Proteins

2. Proteins (Amino Acids) Only 20 naturally-occurring amino acids Only linear structures

3. Functions of Proteins I Catalysts and Metabolic Regulation – Enzymes Protection –Serum antifreeze proteins –Blood coagulation –Antibodies Membrane Transport – Nutrients Signal Transduction – Cell Surface Receptors Structural Support – Collagen

4. Functions of Proteins II Coordinated Motion – Muscle Contraction Genetic Regulation – DNA Binding Proteins Transport – Hemoglobin Generation and Transport of Nerve Impulses Nutrient Storage –Seed proteins –Casein in milk

5. Function of proteins largely due to properties of constituent amino acids

6. Standard Amino Acids (20)

7. Stereochemistry Review Optical Activity

8. Figure 4-9 Diagram of a Polarimeter

9. Rotation of Plane of Polarized Light Dextrorotatory (rotation to the right) = “d” or “+” Levorotatory (rotation to the left) = “l” or “-” Empirical

10. Optically Active Molecules are Asymmetric (i.e. not superimposible on their mirror image)

11. Chiral (Asymmetric) Carbon Four different substituents Stereoisomers C  atoms of amino acids (except glycine) are asymmetric centers!

12. Chiral Centers Give Rise to Enantiomers (non-superimposible mirror images)

13. Distinguishing Stereoisomers Rotation of plane of polarized light (not related to absolute configuration) Cahn-Ingold-Prelog Method (R/S) Fischer Method (projections)

14. Cahn-Ingold-Prelog Method (R/S) (1956)

15. Fischer Convention (1891)

16. Protein Amino Acids

17. Fischer Method/Projections (L/D)

18. L -  -Amino Acids

19. Chirality and Biochemistry Life is Based on Chiral Molecules Biosynthetic processes almost invariably produce pure stereoisomers – e.g. L -amino acids

20. Biological D-amino acids: Bacterial Cell Wall

21. Pharmaceutical Industry Racemic Mixtures

22. Figure 4-12 Benign

23. Figure 4-13 Devastating

24. Chiral Synthesis Goal of Organic Chemistry

25. Amino Acids

26. Non-Polar Hydrophobic Amino Acids

27. Aromatic Amino Acids Non-Polar Polar

28. Polar Amino Acids

29. Negatively Charged (Acidic) Amino Acids

30. Positively Charged (Basic) Amino Acids

31. Notation for 20 Standard AAs

32. Figure 4-8 Greek Nomenclature

33. Dipolar Ions (Zwitterions)

34. Amino Acids can be Buffers

35. Histidine is particularly important for biological function

36. Isoelectric point (pI) pH at which the molecule has a net charge of 0. pI = pKa 1 + pKa 2 2 –Using the pKa’s on either side of the neutral species

37. The Peptide Bond

38. Peptide Bonds Linear Polymers N- Terminus C- Terminus

39. Peptides Dipeptides Tripeptides Oligopeptides Polypeptides

40. Diversity Number = 20 n

41. Variations in length and sequence contribute to the diversity of shapes and biological functions of proteins

42. Nomenclature of Peptides (Primary Structure) L-alanyl-L-seryl-L-aspartic acid [aspartate] Alanylserylaspartate AlaSerAsp ASD

43. Diversity (Tripeptide: 3 x 2 x 1 = 6 arrrangements) Ala Ser AspAla Asp Ser Ser Ala AspSer Asp Ala Asp Ser AlaAsp Ala Ser For 20 amino acids (small peptide): 20! = 2.43 x 10 18

44. Selenocysteine: the 21 st Amino Acid

45. Pyrrolysine: the 22 nd Amino Acid

46. Protein Amino Acid Derivatives

47. Figure 4-14 Some Modified Peptidyl Amino Acids

48. Disulfide Bond Formation (Cystine)

49. Hydroxylation

50. Phosphorylation

51. Acetylation

52. Formylation (amino terminal methionine)

53. Other Modifications Methylation (methyl group) Glycosylation (sugar)

54. Figure 4-15 Biologically Active Amino Acid Derivatives

55. Non-protein Amino Acids

56. Green Fluorescent Protein

57. Box 4-3 figure 1 Aequorea victoria

58. Box 4-3 figure 2

59. Green Fluorescence Protein (GFP) GFP cloned in the early 1990s and expressed in E. coli. http://www.conncoll.edu/ccacad/zimmer/GFP-ww/GFP2.htm

60. GFP-like and GFP variants GFP-like proteins identified in non- bioluminescent organism (i.e. corals) Mutants with faster and brighter fluorescence have since been identified. http://www.conncoll.edu/ccacad/zimmer/GFP-ww/GFP2.htm

61. In vivo Imaging Spatial-temporal imaging of bacterial infection Zhao, M. et al. PNAS. 2001; 98(17): 9814-9818.

62. Cool Green Things! http://www.conncoll.edu/ccacad/zimmer/GFP-ww/GFP4.htm