《有机化学》课程教学资源（教材文献，英文版）CHAPTER 27 AMINO ACIDS, PEPTIDES, AND PROTEINS. NUCLEIC ACIDS

1066 CHAPTER TWENTY-SEVEN Amino Acids, Peptides, and Proteins. Nucleic Acids CH2CHCO2=co2、N 一CH2CH2NH NH Histamine Histamine is responsible for many of the symptoms associated with hay fever and other allergies. An antihistamine relieves these symptoms by blocking the action of histamine PROBLEM 27.9 One of the amino acids in Table 27.1 is the biological precursor to y-aminobutyric acid (4-aminobutanoic acid), which it forms by a decarboxyla tion reaction. Which amino acid is this? The chemistry of the brain and central nervous system is affected by a group of substances called neurotransmitters Several of these neurotransmitters arise from L-tyrosine by structural modification and decarboxylation, as outlined in Figure 27.5 988 issue of the journal of Chemical Education pp.108-111) HO CH NH Tyrosine 3, 4-Dihydroxyphenylalanine HO Ch CHNHO Dopamine HO OH CH,NH, CHNHCH Epinephi FIGURE 27.5 Tyrosine is the biosynthetic precursor to a number of neurotransmi transformation is enzyme-catalyzed. Hydroxylation of the aromatic ring of tyrosine to 3, 4-dihydroxyphenylalanine(L-dopa), decarboxylation of which gives dopamine. Back Forward Main MenuToc Study Guide ToC Student o MHHE Website

Histamine is responsible for many of the symptoms associated with hay fever and other allergies. An antihistamine relieves these symptoms by blocking the action of histamine. PROBLEM 27.9 One of the amino acids in Table 27.1 is the biological precursor to -aminobutyric acid (4-aminobutanoic acid), which it forms by a decarboxyla￾tion reaction. Which amino acid is this? The chemistry of the brain and central nervous system is affected by a group of substances called neurotransmitters. Several of these neurotransmitters arise from L-tyrosine by structural modification and decarboxylation, as outlined in Figure 27.5. N N H CH2CHCO2 NH3 Histidine CO2 enzymes CH2CH2NH2 N N H Histamine 1066 CHAPTER TWENTY-SEVEN Amino Acids, Peptides, and Proteins. Nucleic Acids HO± ±CH2 ±C CO2 H Tyrosine 3,4-Dihydroxyphenylalanine (L-dopa) Dopamine Norepinephrine Epinephrine NH3 HO± ±CH2 ±C CO2 H HO HO± ±CH2CH2NH2 HO± ±C OH H CH2NH2 HO± ±C OH H CH2NHCH3 ¢± ¢± ¢± ¢± T HO T HO T HO T T T T NH3 T FIGURE 27.5 Tyrosine is the biosynthetic precursor to a number of neurotransmitters. Each transformation is enzyme-catalyzed. Hydroxylation of the aromatic ring of tyrosine converts it to 3,4-dihydroxyphenylalanine (L-dopa), decarboxylation of which gives dopamine. Hydroxyla￾tion of the benzylic carbon of dopamine converts it to norepinephrine (noradrenaline), and methylation of the amino group of norepinephrine yields epinephrine (adrenaline). For a review of neurotrans￾mitters, see the February 1988 issue of the Journal of Chemical Education (pp. 108–111). Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website

27.7 Peptide 27.7 PEPTIDES A key biochemical reaction of amino acids is their conversion to peptides, polypeptides and proteins. In all these substances amino acids are linked together by amide bonds The amide bond between the amino group of one amino acid and the carboxyl of another is called a peptide bond. Alanylglycine is a representative dipeptide N-terminal amino acid H3 NCHC-NHCH, CO2 C-terminal amino acid H3 Alanylglycine (Ala-Gly) By agreement, peptide structures are written so that the amino group(as h3N- od that g-amino or HiN-)is at the left and the carboxyl group(as CO2 or CO2 H) is at the right. The ur as their L stereo. left and right ends of the peptide are referred to as the n terminus (or amino terminus) and the C terminus(or carboxyl terminus), respectively. Alanine is the N-terminal amino indicated. The D notation is acid in alanylglycine; glycine is the C-terminal amino acid. a dipeptide is named as an D amino acid is present, and acyl derivative of the C-terminal amino acid. We call the precise order of bonding in a a racemic amino acid is iden- peptide its amino acid sequence. The amino acid sequence is conveniently specified by titled by the prefix Du using the three-letter amino acid abbreviations for the respective amino acids and con- necting them by hyphens. Individual amino acid components of peptides are often referred to as amino acid residues PROBLEM 27. 10 Write structural formulas showing the constitution of each of the following dipeptides. Rewrite each sequence using one-letter abbreviations for the amino acid (a) Gly-Ala (d) Gly-Glu (e)Lys-Gly ()D-Ala-D-Ala SAMPLE SOLUTION (a) Gly-Ala is a constitutional isomer of Ala-Gly. Glycine is the N-terminal amino acid in Gly-Ala; alanine is the c-terminal amino acid Back Forward Main MenuToc Study Guide ToC Student o MHHE Website

27.7 PEPTIDES A key biochemical reaction of amino acids is their conversion to peptides, polypeptides, and proteins. In all these substances amino acids are linked together by amide bonds. The amide bond between the amino group of one amino acid and the carboxyl of another is called a peptide bond. Alanylglycine is a representative dipeptide. By agreement, peptide structures are written so that the amino group (as or H2N±) is at the left and the carboxyl group (as CO2 or CO2H) is at the right. The left and right ends of the peptide are referred to as the N terminus (or amino terminus) and the C terminus (or carboxyl terminus), respectively. Alanine is the N-terminal amino acid in alanylglycine; glycine is the C-terminal amino acid. A dipeptide is named as an acyl derivative of the C-terminal amino acid. We call the precise order of bonding in a peptide its amino acid sequence. The amino acid sequence is conveniently specified by using the three-letter amino acid abbreviations for the respective amino acids and con￾necting them by hyphens. Individual amino acid components of peptides are often referred to as amino acid residues. PROBLEM 27.10 Write structural formulas showing the constitution of each of the following dipeptides. Rewrite each sequence using one-letter abbreviations for the amino acids. (a) Gly-Ala (d) Gly-Glu (b) Ala-Phe (e) Lys-Gly (c) Phe-Ala (f) D-Ala-D-Ala SAMPLE SOLUTION (a) Gly-Ala is a constitutional isomer of Ala-Gly. Glycine is the N-terminal amino acid in Gly-Ala; alanine is the C-terminal amino acid. H3N± N-terminal amino acid NHCH2CO2 C-terminal amino acid H3NCHC CH3 O Alanylglycine (Ala-Gly) 27.7 Peptides 1067 It is understood that -amino acids occur as their L stereo￾isomers unless otherwise indicated. The D notation is explicitly shown when a D amino acid is present, and a racemic amino acid is iden￾tified by the prefix DL. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website

1068 CHAPTER TWENTY-SEVEN Amino Acids, Peptides, and Proteins. Nucleic Acids N-terminal amino acid H3NCH2C--NHCHCO, C-terminal amino acid Glycylalanine(GA) Figure 27.6 shows the structure of Ala-Gly as determined by X-ray crystallogr phy. An important feature is the planar geometry associated with the peptide bond, and the most stable conformation with respect to this bond has the two a-carbon atoms anti to each other. Rotation about the amide linkage is slow because delocalization of the unshared electron pair of nitrogen into the carbonyl group gives partial double-bond char- acter to the carbon-nitrogen bond PROBLEM 27.11 Expand your answer to Problem 27. 10 by showing the struc- tural formula for each dipeptide in a manner that reveals the stereochemistry at the a-carbon atom SAMPLE SOLUTION (a) Glycine is achiral, and so Gly-Ala has only one stereo- genic center, the a-carbon atom of the L-alanine residue. When the carbon chain is drawn in an extended zigzag fashion and L-alanine is the C terminus, its struc- ture is as shown LN Glycyl-L-alanine(Gly-Ala) The structures of higher peptides follow in an analogous fashion. Figure 27.7 gives the structural formula and amino acid sequence of a naturally mccunn known as leucine enkephalin. Enkephalins are pentapeptide components of endorphins polypeptides present in the brain that act as the bodys own painkillers. A second sub- stance,known as methionine enkephalin, is also present in endorphins. Methionine enkephalin differs from leucine enkephalin only in having methionine instead of leucine 拉x FIGURE 27.6 Structural features of the dipeptide L-alanylglycine as determined by X-ray Back Forward Main MenuToc Study Guide ToC Student o MHHE Website

1068 CHAPTER TWENTY-SEVEN Amino Acids, Peptides, and Proteins. Nucleic Acids FIGURE 27.6 Structural features of the dipeptide L-alanylglycine as determined by X-ray crystallography. Figure 27.6 shows the structure of Ala-Gly as determined by X-ray crystallogra￾phy. An important feature is the planar geometry associated with the peptide bond, and the most stable conformation with respect to this bond has the two -carbon atoms anti to each other. Rotation about the amide linkage is slow because delocalization of the unshared electron pair of nitrogen into the carbonyl group gives partial double-bond char￾acter to the carbon–nitrogen bond. PROBLEM 27.11 Expand your answer to Problem 27.10 by showing the struc￾tural formula for each dipeptide in a manner that reveals the stereochemistry at the -carbon atom. SAMPLE SOLUTION (a) Glycine is achiral, and so Gly-Ala has only one stereo￾genic center, the -carbon atom of the L-alanine residue. When the carbon chain is drawn in an extended zigzag fashion and L-alanine is the C terminus, its struc￾ture is as shown: The structures of higher peptides follow in an analogous fashion. Figure 27.7 gives the structural formula and amino acid sequence of a naturally occurring pentapeptide known as leucine enkephalin. Enkephalins are pentapeptide components of endorphins, polypeptides present in the brain that act as the body’s own painkillers. A second sub￾stance, known as methionine enkephalin, is also present in endorphins. Methionine enkephalin differs from leucine enkephalin only in having methionine instead of leucine as its C-terminal amino acid. CO2 H3N O N H H3C H Glycyl-L-alanine (Gly-Ala) N-terminal amino acid NHCHCO2 C-terminal amino acid H3NCH2C O CH3 Glycylalanine (GA) Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website

27.7 Peptide FIGURE 27.7 The structure of the pentapep O hown as (a)a structura molecular model was deter mined by X-ray crystallogr- CH,CH(CH3)2 omitted for clari PROBLEM 27 12 What is the amino acid sequence(using three- letter abbrevia tions)of methionine enkephalin? Show it using one letter abbreviations Peptides having structures slightly different from those described to this point are known. One such variation is seen in the nonapeptide oxytocin, shown in Figure 27.8 Oxytocin is a hormone secreted by the pituitary gland that stimulates uterine contrac- tions during childbirth. Rather than terminating in a carboxyl group, the terminal glycine residue in oxytocin has been modified so that it exists as the corresponding amide. Two cysteine units, one of them the N-terminal amino acid, are joined by the sulfur-sulfur bond of a large-ring cyclic disulfide unit. This is a common structural modification in Recall from Section 15.14 polypeptides and proteins that contain cysteine residues. It provides a covalent bond that compounds of the type between regions of peptide chains that may be many amino acid residues removed from RSH are readily oxidized to Back Forward Main MenuToc Study Guide ToC Student o MHHE Website

27.7 Peptides 1069 PROBLEM 27.12 What is the amino acid sequence (using three-letter abbrevia￾tions) of methionine enkephalin? Show it using one-letter abbreviations. Peptides having structures slightly different from those described to this point are known. One such variation is seen in the nonapeptide oxytocin, shown in Figure 27.8. Oxytocin is a hormone secreted by the pituitary gland that stimulates uterine contrac￾tions during childbirth. Rather than terminating in a carboxyl group, the terminal glycine residue in oxytocin has been modified so that it exists as the corresponding amide. Two cysteine units, one of them the N-terminal amino acid, are joined by the sulfur–sulfur bond of a large-ring cyclic disulfide unit. This is a common structural modification in polypeptides and proteins that contain cysteine residues. It provides a covalent bond between regions of peptide chains that may be many amino acid residues removed from each other. Tyr Gly Gly Phe Leu (b) Tyr Gly Phe Leu Gly (a) HO NH3 S T O X O X N H N H H N X O X O H H CH2 C H N C H C CH2CH(CH3)2 CO2 FIGURE 27.7 The structure of the pentapep￾tide leucine enkephalin shown as (a) a structural drawing and (b) as a molecu￾lar model. The shape of the molecular model was deter￾mined by X-ray crystallogra￾phy. Hydrogens have been omitted for clarity. Recall from Section 15.14 that compounds of the type RSH are readily oxidized to RSSR. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website

CHAPTER TWENTY-SEVEN Amino Acids, Peptides, and Proteins. Nucleic Acids FIGURE 27. 8 The structure of oxytocin, a CH,CNH, disulfide bond between two cysteine residues. One HoNCCH CH f these cysteines is the H N-terminal amino acid and O CHCHCH,CH amide of glycine and is high (CH3),CH lighted in red. There are no OH free carboxyl groups in the H CH all exist HNC、 NH, H 27. 8 INTRODUCTION TO PEPTIDE STRUCTURE DETERMINATION There are several levels of peptide structure. The primary structure is the amino acid sequence plus any disulfide links. With the 20 amino acids of Table 27.1 as building blocks, 20- dipeptides, 20 tripeptides, 20 tetrapeptides, and so on, are possible. Given a peptide of unknown structure, how do we determine its amino acid sequence? We'll describe peptide structure determination by first looking at one of the great achievements of biochemistry, the determination of the amino acid sequence of insulin by Frederick Sanger of Cambridge University(England). Sanger was awarded the 1958 Nobel Prize in chemistry for this work, which he began in 1944 and completed 10 years second Nobel Prize in 1980 later. The methods used by Sanger and his coworkers are, of course, dated by now, but the overall strategy hasnt changed very much. We'll use Sanger's insulin work to ori- ncing nucleic acids. gers strategy for nucle ent us with respect to strategy, then show how current methods of protein sequencing cid sequencing will be de- have evolved from it scribed in Section 27 29 Sanger's strategy can be outlined as follows: 1. Determine what amino acids are present and their molar ratios 2. Cleave the peptide into smaller fragments, separate these fragments, and determine the amino acid composition of the fragments 3. Identify the N-terminal and the C-terminal amino acid in the original peptide and in each fragment 4. Organize the information so that the amino acid sequences of small fragments can be overlapped to reveal the full sequence. 27.9 AMINO ACID ANALYSIS The chemistry behind amino acid analysis is nothing more than acid-catalyzed hydroly sis of amide(peptide)bonds. The peptide is hydrolyzed by heating in 6 M hydrochloric then separated by ion-exchange chromatography, which separates e is mixture is acid for about 24 h to give a solution that contains all the amino acids. TI acids mainly according to their acid-base properties. As the amino acids leave the chro- matography column, they are mixed with ninhydrin and the intensity of the ninhydrin Back Forward Main MenuToc Study Guide ToC Student o MHHE Website

27.8 INTRODUCTION TO PEPTIDE STRUCTURE DETERMINATION There are several levels of peptide structure. The primary structure is the amino acid sequence plus any disulfide links. With the 20 amino acids of Table 27.1 as building blocks, 202 dipeptides, 203 tripeptides, 204 tetrapeptides, and so on, are possible. Given a peptide of unknown structure, how do we determine its amino acid sequence? We’ll describe peptide structure determination by first looking at one of the great achievements of biochemistry, the determination of the amino acid sequence of insulin by Frederick Sanger of Cambridge University (England). Sanger was awarded the 1958 Nobel Prize in chemistry for this work, which he began in 1944 and completed 10 years later. The methods used by Sanger and his coworkers are, of course, dated by now, but the overall strategy hasn’t changed very much. We’ll use Sanger’s insulin work to ori￾ent us with respect to strategy, then show how current methods of protein sequencing have evolved from it. Sanger’s strategy can be outlined as follows: 1. Determine what amino acids are present and their molar ratios. 2. Cleave the peptide into smaller fragments, separate these fragments, and determine the amino acid composition of the fragments. 3. Identify the N-terminal and the C-terminal amino acid in the original peptide and in each fragment. 4. Organize the information so that the amino acid sequences of small fragments can be overlapped to reveal the full sequence. 27.9 AMINO ACID ANALYSIS The chemistry behind amino acid analysis is nothing more than acid-catalyzed hydroly￾sis of amide (peptide) bonds. The peptide is hydrolyzed by heating in 6 M hydrochloric acid for about 24 h to give a solution that contains all the amino acids. This mixture is then separated by ion-exchange chromatography, which separates the amino acids mainly according to their acid–base properties. As the amino acids leave the chro￾matography column, they are mixed with ninhydrin and the intensity of the ninhydrin 1070 CHAPTER TWENTY-SEVEN Amino Acids, Peptides, and Proteins. Nucleic Acids Sanger was a corecipient of a second Nobel Prize in 1980 for devising methods for se￾quencing nucleic acids. Sanger’s strategy for nucleic acid sequencing will be de￾scribed in Section 27.29. H H O H NH C H CH2CNH2 O O 0 0 O 0 H OH H H O X H2NCCH2 O X C X O W CH2 O X CH2 W H N H N 0 O N H CH3CHCH2CH3 CH2 HN ± ± ± W NH2 N N H C X O C H N O X H2NC (CH3)2CH S S FIGURE 27.8 The structure of oxytocin, a nonapeptide containing a disulfide bond between two cysteine residues. One of these cysteines is the N-terminal amino acid and is highlighted in blue. The C-terminal amino acid is the amide of glycine and is high￾lighted in red. There are no free carboxyl groups in the molecule; all exist in the form of carboxamides. Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website