Amino Acids and Peptides

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. Diagram of a Polarimeter Figure 4-9

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. Benign Figure 4-12

23. Devastating Figure 4-13

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. Greek Nomenclature Figure 4-8

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 = pKa1 + pKa2 2 • Using the pKa’s on either side of the neutral species

37. The Peptide Bond

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

39. Peptides Dipeptides Tripeptides Oligopeptides Polypeptides

40. Diversity Number = 20n

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) For 20 amino acids (small peptide): 20! = 2.43 x 1018

44. Selenocysteine: the 21st Amino Acid

45. Pyrrolysine: the 22nd Amino Acid

46. Protein Amino Acid Derivatives

47. Some Modified Peptidyl Amino Acids Figure 4-14

48. Disulfide Bond Formation(Cystine)

49. Hydroxylation

50. Phosphorylation