AMINO ACIDS, PEPTIDES, AND PROTEINS. NUCLEIC ACIDS 757 27.10 (b) Alanine is the N-terminal amino acid in Ala-Phe Its carboxyl group is joined to the nitrogen of phenylalanine by a peptide bo H3NCHC--NHCHCO Alanine (c) The positions of the amino acids are reversed in Phe-Ala. Phenylalanine is the N terminus and alanine is the C terr HANCHC-NHCHCO, C6HSCH Alanine (d) The carboxyl group of glycine is joined by a peptide bond to the amino group of glutamic acid H3NCHC-NHCHCO CHCH CO The dipeptide is written in its anionic form because the carboxyl group of the side chain is ionized at pH 7. Alternatively, it could have been written as a neutral zwitterion with a CH,CH, CO, H side chain (e) The peptide bond in Lys-Gly is between the carboxyl group of lysine and the amino group of H3NCHC--NHCH, CO, KG H,NCH,CH, CH,CH Glycine The amino group of the lysine side chain is protonated at pH 7, and so the dipeptide is written here in its cationic form it could have also been written as a neutral zwitterion chain H,NCH,CH,Ch,CH (f) Both amino acids are alanine in D-Ala-D-Ala. The fact that they have the d configuration has no effect on the constitution of the dipeptide. H-NCHC-NHCHCO D-A-D-A H3 Alanine Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
27.10 (b) Alanine is the N-terminal amino acid in Ala-Phe. Its carboxyl group is joined to the nitrogen of phenylalanine by a peptide bond. (c) The positions of the amino acids are reversed in Phe-Ala. Phenylalanine is the N terminus and alanine is the C terminus. (d) The carboxyl group of glycine is joined by a peptide bond to the amino group of glutamic acid. The dipeptide is written in its anionic form because the carboxyl group of the side chain is ionized at pH 7. Alternatively, it could have been written as a neutral zwitterion with a CH2CH2CO2H side chain. (e) The peptide bond in Lys-Gly is between the carboxyl group of lysine and the amino group of glycine. The amino group of the lysine side chain is protonated at pH 7, and so the dipeptide is written here in its cationic form. It could have also been written as a neutral zwitterion with the side chain H2NCH2CH2CH2CH2. ( f ) Both amino acids are alanine in D-Ala-D-Ala. The fact that they have the D configuration has no effect on the constitution of the dipeptide. NHCHCO2 d-A-d-A CH3 H3NCHC CH3 O Alanine Alanine H3NCHC KG H3NCH2CH2CH2CH2 O Lysine NHCH2CO2 Glycine H3NCH2C NHCHCO2 GE CH2CH2CO2 O Glycine Glutamic acid H3NCHC FA C6H5CH2 O Phenylalanine NHCHCO2 CH3 Alanine H AF 3NCHC CH3 O Alanine NHCHCO2 CH2C6H5 Phenylalanine AMINO ACIDS, PEPTIDES, AND PROTEINS. NUCLEIC ACIDS 757 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
758 AMINO ACIDS, PEPTIDES, AND PROTEINS. NUCLEIC ACIDS 27.11(b) When amino acid residues in a dipeptide are indicated without a prefix, it is assumed that the configuration at the a carbon atom is L. For all amino acids except cysteine, the L configura tion corresponds to S. The stereochemistry of Ala-Phe may therefore be indicated for the zigzag conformation as shown. H H C The L configuration corresponds to S for each of the stereogenic centers in Ala-Phe. (c) Similarly, Phe-Ala has its substituent at the N-terminal amino acid directed away from us, whereas the C-terminal side chain is pointing toward us, and the L configuration corresponds to s for each stereogenic center. OH,C H H-N C6HsCH, (d) There is only one stereogenic center in Gly-Glu. It has the L (or S) configuration. CH,CH,CO H (e) In order for the N-terminal amino acid in Lys-Gly to have the L (or S)configuration, its side chain must be directed away from us in the conformation indicated H-N H,NCH, CH, CH, CH, H (f) The configuration at both a-carbon atoms in D-Ala-D-Ala is exactly the reverse of the config- uration of the stereogenic centers in parts(a)through(e). Both stereogenic centers have the D H CH 27.12 Figure 27.7 in the text gives the structure of leucine enkephalin Methionine enkephalin differs from it only with respect to the C-terminal amino acid. The amino acid sequences of the two pentapep- Tyr-Gly-Gly-Phe-Leu Tyr-Gly-Gly-Phe-Met Leucine enkephalin Methionine enkephalin The peptide sequence of a polypeptide can also be expressed using the one-letter abbreviations listed in text Table 27.1. Methionine enkephalin becomes YGGFM Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
27.11 (b) When amino acid residues in a dipeptide are indicated without a prefix, it is assumed that the configuration at the carbon atom is L. For all amino acids except cysteine, the L configuration corresponds to S. The stereochemistry of Ala-Phe may therefore be indicated for the zigzag conformation as shown. The L configuration corresponds to S for each of the stereogenic centers in Ala-Phe. (c) Similarly, Phe-Ala has its substituent at the N-terminal amino acid directed away from us, whereas the C-terminal side chain is pointing toward us, and the L configuration corresponds to S for each stereogenic center. (d) There is only one stereogenic center in Gly-Glu. It has the L (or S) configuration. (e) In order for the N-terminal amino acid in Lys-Gly to have the L (or S) configuration, its side chain must be directed away from us in the conformation indicated. ( f ) The configuration at both -carbon atoms in D-Ala-D-Ala is exactly the reverse of the configuration of the stereogenic centers in parts (a) through (e). Both stereogenic centers have the D (or R) configuration. 27.12 Figure 27.7 in the text gives the structure of leucine enkephalin. Methionine enkephalin differs from it only with respect to the C-terminal amino acid. The amino acid sequences of the two pentapeptides are The peptide sequence of a polypeptide can also be expressed using the one-letter abbreviations listed in text Table 27.1. Methionine enkephalin becomes YGGFM. Tyr-Gly-Gly-Phe-Leu Leucine enkephalin Tyr-Gly-Gly-Phe-Met Methionine enkephalin H3N H O N H H CH3 CH3 CO2 H3N H3NCH2CH2CH2CH2 O N H H CO2 H3N CH2CH2CO2 O N H H CO2 H3N C6H5CH2 OH3C N H H H CO2 H3N H3C O N H H H CO2 CH2C6H5 758 AMINO ACIDS, PEPTIDES, AND PROTEINS. NUCLEIC ACIDS Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website
AMINO ACIDS, PEPTIDES, AND PROTEINS. NUCLEIC ACIDS 759 27.13 Twenty-four tetrapeptide combinations are possible for the four amino acids alanine(A), glycine (G), phenylalanine(F), and valine (V). Remember that the order is important; AG is not the same peptide as GA. Using the one-letter abbreviations for each amino acid the possibilities are AGFV ACⅤF AFGV AFVG AVGE AVG GAFV GAVF GFAV GVA GVFA GVAF FAGV FAVG FVAG FVGA FGAF FGFA VAGF VAFGⅤ GAF GFAⅤFA 27 14 Chymotrypsin cleaves a peptide selectively at the carboxyl group of amino acids that have aromatic side chains. The side chain of phenylalanine is a benzyl group, CBH_ CH2. If the dipeptide isolated after treatment with chymotrypsin contains valine (V) and phenylalanine(F), its sequenc beⅤF H3 NCHC--NHCHC-—计 Rest of peptide chymotrypsin NCHC-NHCHCO+ Rest of peptide (CH3)2CH CHCH (CH3),CH H,C6H5 alanine Valinylphenylalanine(VF) The possible sequences for the unknown tetrapeptide are VFAG and VFGa 27.15 The Edman degradation removes the N-terminal amino acid, which is identified as a phenylthiohy danton derivative. The first Edman degradation of Val-Phe-Gly-Ala gives the phenylthiohydantoin derived from valine; the second gives the phenylthiohydantoin derived from phenylalar CaH CsH second Val-Phe-Gly-Ala Edman degradation Phe-Gly-Ala SAo Edman degradation. Gly-Ala CH(CH3)2 CH, CAH5 27.16 Lysine has two amino groups. Both amino functions are converted to amides on reaction with benzyloxycarbonyl chloride H2NCHCO2+ 2C6H_ CH,OCCI C6HS CH,OCNHCHCO,H H,NCH, CH, CHCH C6HSCHOCNHCH, CH,CH,CH We therefore need to protect the amino group of alanine and the carboxyl group of leucine leucine 27 17 The peptide bond of Ala-Leu connects the carboxyl group of alanine and the amino group of Protect the amino group of alanine as its benzyloxycarbonyl derivative H3NCHCO2 CHsCH,OCCl CAHCH,OCNHCHCO,H CH Alanine Benzyloxycarbonyl Z-Protected alanine Back Forward Main Menu TOC Study Guide Toc Student OLC MHHE Website
27.13 Twenty-four tetrapeptide combinations are possible for the four amino acids alanine (A), glycine (G), phenylalanine (F), and valine (V). Remember that the order is important; AG is not the same peptide as GA. Using the one-letter abbreviations for each amino acid the possibilities are AGFV AGVF AFGV AFVG AVGF AVFG GAFV GAVF GFAV GFVA GVFA GVAF FAGV FAVG FVAG FVGA FGAF FGFA VAGF VAFG VGAF VGFA VFAG VFGA 27.14 Chymotrypsin cleaves a peptide selectively at the carboxyl group of amino acids that have aromatic side chains. The side chain of phenylalanine is a benzyl group, C6H5CH2 —. If the dipeptide isolated after treatment with chymotrypsin contains valine (V) and phenylalanine (F), its sequence must be VF. The possible sequences for the unknown tetrapeptide are VFAG and VFGA. 27.15 The Edman degradation removes the N-terminal amino acid, which is identified as a phenylthiohydantoin derivative. The first Edman degradation of Val-Phe-Gly-Ala gives the phenylthiohydantoin derived from valine; the second gives the phenylthiohydantoin derived from phenylalanine. 27.16 Lysine has two amino groups. Both amino functions are converted to amides on reaction with benzyloxycarbonyl chloride. 27.17 The peptide bond of Ala-Leu connects the carboxyl group of alanine and the amino group of leucine. We therefore need to protect the amino group of alanine and the carboxyl group of leucine. Protect the amino group of alanine as its benzyloxycarbonyl derivative. H3NCHCO2 CH3 Alanine C6H5CH2OCCl O Benzyloxycarbonyl chloride C6H5CH2OCNHCHCO2H CH3 O Z-Protected alanine O H2NCHCO2 2C6H5CH2OCCl O O C6H5CH2OCNHCHCO2H C6H5CH2OCNHCH2CH2CH2CH2 H2NCH2CH2CH2CH2 Val-Phe-Gly-Ala Phe-Gly-Ala first Edman degradation second Edman degradation S HN CH(CH3)2 O Gly-Ala S HN CH2C6H5 N O C6H5 N C6H5 CH2C6H5 NHCHC O H3NCHC O (CH3)2CH Valine Phenylalanine CH2C6H5 NHCHCO O H3NCHC O (CH3)2CH Valinylphenylalanine (VF) Rest of peptide Rest of peptide chymotrypsin AMINO ACIDS, PEPTIDES, AND PROTEINS. NUCLEIC ACIDS 759 Back Forward Main Menu TOC Study Guide TOC Student OLC MHHE Website