Chapter 18 Amino Acids, Peptides, and Proteins ( 氨基酸、肽、蛋白质 )

1. Chapter 18 Amino Acids, Peptides, and Proteins (氨基酸、肽、蛋白质)

2. Amino acids Most of the chiral centers in natural α-amino acids are (S)-configurations. The relative configuration of most α-Amino Acids are L-. L-amino acids

3. Peptides and proteins are polymers of amino acids linked together by amide bonds

4. The 20 standard α-amino acids R = hydrocarbyl R为烃基的氨基酸 Glycine, Gly 甘氨酸 Alanine, Ala 丙氨酸 Valine, Val 缬氨酸 Isoleucine, Ile 异亮氨酸 Phenylalanine, Phe 苯丙氨酸 Leucine, Leu 亮氨酸

5. Hydroxy-Containing Amino Acids含羟基氨基酸 Serine, Ser 丝氨酸 Threonine, Thr 苏氨酸 Tyrosine, Tyr 酪氨酸

6. Sulfur-Containing Amino Acids 含硫氨基酸 Cysteine, Cys 半胱氨酸 Methionine, Met 蛋氨酸

7. Acidic Amino Acids 酸性氨基酸 Glutamic acid, Glu, 谷氨酸 Aspartatic acid, Asp, 门冬氨酸 Amides of Acidic Amino Acids 酸性氨基酸的酰胺 Glutamine, Gln, 谷氨酰胺 Asparagine, Asn, 门冬酰胺

8. Basic Amino Acids 碱性氨基酸 Lysine, Lys 赖氨酸 Arginine, Arg 精氨酸 Histidine, His 组氨酸

9. Proline, Pro 脯氨酸 Tryptophan, Try 色氨酸 The 8 essential amino acids (必需氨基酸，八种)

10. Acid–Base Properties of Amino Acids pKa1 pKa2 The isoelectric point (pI，等电点) of an amino acid is the pH at which it has no net charge.

11. isoelectric point (pI，等电点) Acidic amino acids: aspartic acid 门 冬氨酸(2.8), glutamic acid 谷氨酸(3.2), Neutral amino acids: (5.0~6.3) Basic amino acids: lysine 赖氨酸 (9.7) arginine 精氨酸 (10.8) histidine 组氨酸 (7.6)

12. Problem 24-4: • Draw the structure of the predominant form of • Valine at pH 11 • Proline at pH 2 • Arginine at pH 7 • Glutamic acid at pH 7

13. A mixture of amino acids can be separated by Electrophoresis (电泳) on the basis of their pI values pH 6 buffer solution缓冲溶液 Ninhydrin(茚三酮) is used to detect the individual amino acids Ninhydrin(茚三酮) 氨基酸的显色剂

14. A mixture of amino acids can also be separated on the basis of polarity

15. Reactions of α-amino acids 1. Acylation of amino group PhCH2OCOCl, CbzCl: benzyl chloroformate, 氯甲酸苄酯, 保护氨基

16. 2. Alkylation Application：氨基酸的N-端的测定 3. Reaction with HNO2

17. 4. Reaction with ninhydrin 茚三酮 deep purple 深紫色 Note: proline can not give this phenomenon.

19. 5. Esterification of the carboxy group Application：保护氨基酸的羧基

20. Synthesis of α-amino acids 1. Reductive amination of α-ketoacid 24-5A α-ketoacid (酮酸) α-amino acid A biomimetic synthesis 生物模拟合成

21. α-ketoglutaric acid α-氧代戊二酸 L-glutamic acid L-谷氨酸 NADH：烟酰胺腺嘌呤二核苷酸，还原态 NAD+：氧化态

22. 2. Amination of α-halo acids HVZ reaction Acceptable yield • A large excess of amine was used; • The adjacent carboxylate ion in the product reduces the nucleophilicity of the amino group.

24. 3. The Gabriel-malonic ester synthesis This method is a modification of the Gabriel synthesis of amines. The yields are usually high and the products are easily purified.

25. 4. The Strecker synthesis

26. Resolution of D,L-amino acids (氨基酸的拆分) Acylase 酰化酶，只使L-乙酰氨基酸脱乙酰基

27. Peptides 肽 N-terminus N-端 C-terminus C-端

28. Peptide Bond (肽键) alanylglycylalanine; ala-gly-ala; AGA 丙氨酰甘氨酰丙氨酸, 丙甘丙

29. Formation of Disulfide Bonds 半胱氨酸 胱氨酸 Disulfides can be reduced to thiols

30. The disulfide bridge in proteins contributes to the overall shape of a protein 牛胰岛素

31. Synthesis of peptides (24-10, 11) Problem: Synthesis of ala-gly

32. Solution-phase Peptide Synthesis 液相合成 ala-gly

33. Solid-phase Peptide Synthesis 固相合成 Merifield automated solid-phase synthesis of a tripeptide di-tert-butyldicarbonate， Boc2O 二碳酸二叔丁酯；Boc酸酐

36. ………………… Amino acids can be added to the growing C-terminal end by repeating these two steps

37. 6 N HCl protein amino acids 100°C 24 h Peptide structure determination Step 1: cleavage of the disulfide bridges Step 2: determine the number and kinds of amino acids in the peptide or protein Step 3: sequencing the peptides ----terminal residue analysis

39. Sequencing from the N-terminus: the Edman degradation + NH2-peptide ……………

40. The C-terminal amino acid can be identified by treating the protein with carboxypeptidase（羧肽酶）

41. Partial hydrolysis (部分水解) Problem: acid-catalysed hydrolysis of oxytocin (after cleavage of the disulfide bond) gives a mixture that include the following peptides: Ile-Gln-Asn-Cys Gln-Asn-Cys-Pro Pro-Leu-gly.NH2 Cys-Tyr-Ile-Gln-Asn Cys-Pro-Leu-Gly Propose the complete sequence of oxytocin. Answer: Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly.NH2

42. Secondary Structure of Proteins 蛋白质的二级结构 Describe the conformation of segments of the backbone chain of a peptide or protein. Three factors determine the choice of secondary structure: • the regional planarity about each peptide bond • maximization of the number of peptide groups that • engage in hydrogen bonding • adequate separation between nearby R groups

43. The a-Helix (螺旋结构) Is Stabilized by Hydrogen Bonds Prolines are helix breakers

44. Two Types of b-Pleated Sheets (折叠结构)

45. Most globular proteins(球蛋白) have random coil (线团) conformations

46. The tertiary structure is（三级结构） the three-dimensional arrangement of all the atoms in the protein

47. The tertiary structure is defined by the primary structure The stabilizing interactions include covalent bonds, hydrogen bonds, electrostatic attractions, and hydrophobic interactions Disulfide bonds are the only covalent bonds that can form when a protein folds Proteins that have more than one peptide chain are called oligomers（低聚物）

48. The quaternary structure（四级结构） The quaternary structure refers to the association of two or more peptides chains in the complete protein.

49. Summary • 20 standard amino acids • Isoelectric point, acid–base properties • Protection of amino and carboxyl groups • Reaction with ninhydrin • Lab synthesis of amino acids (4 methods) • Structure of peptides • Synthesis of peptides (solution and solid synthesis) • Analysis of peptides • Structure of proteins

50. assignment • 24-34, 35, 36, 43, 44