AMINO ACIDS

1. AMINO ACIDS

2. Structure of α-amino acids α-carbon Aminoacetic acid = glycine

3. Dipolar nature of α-amino acids Glycine Propylamine Propionic acid μ = 14 D μ = 1.7 D μ = 1.4 D

4. Dipolar nature of α-amino acids Electron density for uncharged alanine and zwitterion

5. Dipolar nature of α-amino acids determines their properties • They are solids with high melting points – • glycine m.p. 262°C • They are much better soluble in water • than in organic solvents • Their dipole moments are high • They are less acidic than carboxylic acids • and less basic than amines

6. Acid-base equilibria of α-amino acids Anion Zwitterion Cation pH > pI pH = pI pH < pI pI – isoelectric point

7. At pH correspondig to pI value of given amino acid: • Predominating form is zwitterion • Molecule is electrically uncharged • Amino acid shows the lowest solubility in water • At pH < pI predominating form is a cation • At pH > pI predominating form is an anion

8. General structure of 20 protein α-amino acids R = side chain

9. Chirality of protein α-amino acids (α-carbon is stereogenic centre) R = side chain

10. Configuration of α-L-amino acids L-amino acid L-glyceraldehyde (S)-absolute configuration with exception of cysteine

11. L-amino acids with hydrophobic side chains (neutral amino acids)

12. L-amino acids with electrically charged side chains Basic amino acids Acidic amino acids

13. L-amino acids with polar uncharged side chains

14. L-amino acids with other side chains

15. More than 700 nonprotein amino acids are found in nature γ-Aminobutyric acid (GABA) is found in the brain and acts as a neurotransmitter Homocysteine is found in the blood and is linked to coronary heart disease

16. More than 700 nonprotein amino acids are found in nature Thyroxine is found in the thyroid gland and acts as a hormone Selenocysteine and pyrrolysine are amino acids found in some organisms

17. Acid-base equilibria of amino acids pI = 6 Titration of alanine

18. Acid-base equilibria of amino acids Titration of lysine and glutamic acid

19. Separation of amino acids by electrophoresis cathode anode

20. Analytical reactions of amino acids van Slyke reaction (number of equivalents of primary amino groups can be determined by measuring volume of nitrogen evolved)

21. Analytical reactions of amino acids Reaction with ninhydrin Ruhemann’s purple

22. Reaction of protein amino acids with ninhydrin

23. Absorption UV spectra of aromatic amino acids

24. Syntheses of amino acids Amination of -halogenocarboxylic acids

25. Syntheses of amino acids Strecker synthesis

26. Syntheses of amino acids Gabriel synthesis

27. Syntheses of amino acids Malonate synthesis

28. Syntheses of amino acids Malonate synthesis, continued

29. Syntheses of amino acids Phthalimidomalonate synthesis

30. Syntheses of amino acids Phthalimidomalonate synthesis, continued

31. Syntheses of amino acids Reductive amination of -ketoacids

32. Asymmetric syntheses of amino acids (S)-Phenylalanine, is prepared in 98.7% purity contaminated by only 1.3% of the (R) enantiomer when a chiral rhodium catalyst is used Knowles received the 2001 Nobel Prize in Chemistry

33. Asymmetric syntheses of amino acids Most effective catalysts for enantioselective amino acid synthesis are coordination complexes of rhodium(I) with cyclooctadiene (COD) and a chiral diphosphine such as (R,R)-1,2-bis(o-anisylphenylphosphine)ethane, the DiPAMP ligand

34. Reactions of amino acids Salt formation in alkaline solution

35. Reactions of amino acids Salt formation in acidic solution

36. Reactions of amino acids Esterification of carboxylic group Alcohols frequently used for ester formation

37. Reactions of amino acids Acylation of amino group N-protected valine

38. Reactions of amino acids Amide formation Amide bond = Peptide bond

39. PEPTIDES

40. Two different amino acids can form two dipeptides

41. Convention for writing peptides: • N-terminal amino acid on the left • Amino acid with the free –NH2 group • C-terminal amino acid on the right • Amino acid with the free –CO2H group • The name of the peptide is indicated using abbreviations: • Alanylserine is abbreviated Ala-Ser or A-S • Serylalanine is abbreviated Ser-Ala or S-A

42. Three different amino acids can form six tripeptides Example: Asp, Gly, Ser as components of tripeptide can be linked in six ways yielding molecules of different properties Asp-Gly-Ser Asp-Ser-Gly Gly-Asp-Ser Gly-Ser-Asp Ser-Asp-Gly Ser-Gly-Asp

43. Peptide bond • Amide nitrogens are nonbasic because their unshared electron pair is delocalized by interaction with the carbonyl group • The overlap of the nitrogen p orbital with the p orbital of the carbonyl group imparts a certain amount of double-bond character to the C-N bond and restricts rotation around it • The amide bond is planar • The N-H is oriented 180º to the C=O

44. Peptide structure

45. Angiotensin II – blood-pressure regulating hormone is octapeptide H-Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-OH (DRVYIHPF) N-terminal residue C-terminal residue

46. Disulfide bonds in peptides A covalent bond in peptides formed between two cysteine residues It links two chains of peptides together or…

47. Disulfide bonds in peptides • creates loops within a single chain of peptides • Vasopressin (nonapeptide), an antidiuretic hormone found in the pituitary gland

48. Determination of a peptide structure • What amino acids are present? • How much of each is present? • In what sequence do amino acids occur?

49. Peptide analysis Determination of amino acid composition: H-Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-OH 6N HCl, H2O 100C, 24 h Hydrolysis of all peptide bonds Mixture of component amino acids Amino acid analyser

50. Amino acid analyser