23B 23B.1 23B.1.1 23B.1.2 23B.2 23B.2.1 23B.2.2 a b 23B.3 23B.3.1 23B.3.2 23B.4 23B.4.1 23B.4.2 23B.4.3 23B.5 23B.5.1 23B.5.2 23B.6 23B.6.1 a b c Edman d e 23B.6.2 23B.6.3 23B.7 23B.7.1 a b c 23B.7.2 23B.7.3 1
protein peptide n 2 n 2 23B.1 α keratin collagen enzyme 23C 23E 23B.1.1 αamino acid 23.2 zwitterion α L Fischer 2 D 2 C C 2 2 C 2 C 2 C 2 3 C 2 L! 23B.2 Lα 2
23B.1 20 23B.1 α pk a (a) C C 2 2 3 (glycine: Gly,G) 3 (alanine: Ala, A) 3 2.34, 9.60 C 3 2.34, 9.69 C 2 CMe 2 (valine: Val, V) 2.32, 9.62 C 2 3 3 (leucine: Leu, L) C 2 2.36, 9.60 C 3 C 2 (isoleucine: Ileu, I) 2.36, 9.68 3 C 2 (phenylalanine: Phe, F) 2.16, 9.18 CMe 2 C 2 C 3 3 C 2 C 2 C 2 Me (methionine: Met, M) 2.34, 9.69 C 2 2 (proline: Pro, P) 1.99, 10.60 (b) C 2 3 (serine: er, ) 3 2.21, 9.15 C 2 C 2 3 C C 2 2 (asparagine: (glutamine: Gln, Q) 3 Asn, ) 3 2.17, 8.84 3 2.02, 8.84 C 2 C() 2 C 2 C 2 C() 2 C 3 (threonine: Thr, T) 2.63, 9.10 C 2 C 2 (tyrosine: Tyr, Y) 2.20, 9.11, 10.07 (tryptophan: Trp, W) 2.38, 9.39 3 C 2 C 2 (cysteine: Cys, C) 1.92, 10.46, 8.35 (c) C 2 3 (aspartic acid: Asp, D) 3 2.09, 9.82, 3.86 C 2 C 2 C 2 C 2 C 2 C 2 (glutamic acid: Glu, E) 2.19, 9.67, 4.25 (d) C 2 (lysine: Lys, K) 3 2.18, 8.95, 10.79 3 (C 2 ) 4 3 C 2 (C 2 ) 3 C 2 (arginine: Arg, )) 2.17, 9.04, 12.48 2 3 C 2 (histidine: is, ) 1.82, 9.17, 6.04 p 7.0 pk a 3
23B.1 (a) p 7 (b) p 8 10 c d pk a 10 essential amino acid 23B.1 23B.1 L, Me 2 L 2 L 23B.1 L, (a) (b) (c) 23B.2 p 2 p 11 (a) (b) (c) (d) 23B.1.2 pk a1 = 2, pk a2 = 9 pk a1 pk a 4
pk a2 C 2 pk a p 7 pk a pk a p 4 pk a 1.82 6.04 9.17 p p = pk a 6 p.99 endersonasselbalch 23B.3 p 3 C 2 pk a1 = 1.82 3 C 2 C 2 3 pk a2 = 6.04 pk a3 = 9.17 2 C 2 (p < 1) (p 3~5) (p 7~8) (p > 8) 23B.3 p p isoelectric point, pi pi = (pk a1 pk a2 )/2 pk a pk a 23B.2 pi = (pk a1 pk a2 )/2 pi = (pk a2 pk a3 )/2 pk a1 pk a2 pk a1 pk a2 pi pi = 2.93 5
pk 1 = 2.09 pk C 2 C 2 = 3.86 2 3 3 3 C 2 C 2 C 2 C 2 L pk C 3 = 9.82 2 2 C 2 C 2 C 2 C 2 C 2 pk a1 1 pk a2 pk a3 1 pk a2 pk a3 pi = 9.87 3 pk 1 = 2.18 C 2 3 (C 2 ) 4 3 C 2 23B.3 (a) (b) (c) (C 2 ) 4 3 pk 2 = 8.95 L 2 C 2 (C 2 ) 4 3 pk 3 = 10.79 2 C 2 (C 2 ) 4 2 23B.4 23B.2.1 Lα 2 L 2 C C 2 2 AD 3 3 2 C C 2 L 3 C 2 ' C 2 C 2 3 ' C 2 23B.2.2 a 6
23B.3.1 2 PBr 3 P ell Volhard Zelinsky C 3 C 2 C 2 Br 2 PBr 3 Br C 3 CC 2 3 2 3 C 3 CC 2 Br C(C 2 Et) 2 K Gabriel C(C 2 Et) 2 1) aet, Et 2) X 3) 3, 2 2Et C(C 2 ) 2 CC 2 C 2 3, 2 C 2 C 2 3 CC 2 23B.4 2 Ac C(C 2 Et) 2 1) aet, Et 3, 2 2) X Ac C(C 2 Et) 2 2Et Ac C 2 3 CC 2 trecker trecker C 4 Cl ac 4 Cl, ac 2 C 3, 2 3 C 2 trecker 7
23B.5 b Lα BIAP h(i) C 2 C()Ph 2 (3~4 atm), Et 48 h ()BIAP C 2 C()Ph h(i) 97%, ee 100% C 2 2 3 () Ph Ph P Me h Cl 4 P Me Ph Ph ()BIAP h(i) 2 BIAP Ph Ph Ph tbu Br * (0.05 mol%) 50% K/ 2 / MePh, 0 C, 2 h Ph tbu Ph Ph () 98%, ee 99% 3 2 Ph C 2 () 23B.3.1 optical resolution 11 11.4.3 8
()1 23B.5 3 3 Me C 2 () Me C 2 () Ac 2 Me Ac C 2 () Me Ac () C 2 2 Ph ()1 Me Ac Ph Ac Ph Me C 2 () 3 Me Me C 2 () 3 Me Ac Me C 2 3 Ph Me Ac Me C 2 3 Ph Me () () / 2 / 2 3 Me C 2 () 3 Me C 2 () Ph 2 Me 23B.5 (±) 9
kinetic resolution L D 23B.2.2 electrophoresis p 23B.6 pi p pi pi pi pi p pi 6.02 pi 3.22 pi 10.76 p 6.0 Ala Glu Arg Arg Ala Glu (pi = 10.76) (pi = 6.02) (pi = 3.22) 23B.6 10
2 3 CC 2 C C 2 3 ninhydrin (! max 570 nm) 23B.6 p 6.0 (a) (b) (c) 23B.7 paper chromatography thin-layer chromatography chromatography 2.2 mobile phase stationary phase ion-exchange chromatography 23B.7 11
23B.7 23B.8 p 6 3 a cationexchange resinc 2 Me 3 3 a 3 a 3 a C 2 C C 2 C C C 2 C C 2 C C 2 C C 2 C C 2 C C 2 C C 2 C C 2 C C 2 C C 2 C 3 a 3 a 23B.8 amino acid analyzer amino acid 12
residue C 2 1 2 3 C 23B.8 p 6 p 10 (a) AlaGlyer (b) erargasn 23B.4.1 sp 2 C 40 C s s s s s C C C 120 120 6 13
23B.9 23B.4.2 14 14.7.2 2 2 C 2 CC 2 3 cysteine C 2 CC 2 CCC 2 2 3 3 cystine 23B.4.3 14
2 C 2 Ph Me aspartame 2 C 2 C 2 glutathione C 2 2 Ph enkephalin = C 2 Me: [met]enkephalin = CMe 2 : [leu]enkephalin Arg-Pro-Pro-Gly-Phe-er-Pro-Phe-Arg bradykinin C 2 Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly- 2 vasopressin Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly- 2 oxytocin 21 30 15
A GlyIle ValGluGlnCysCysAlaerValCyserLeuTyrGlnLeuGluAsnTyrCysAsn B Phe ValAsnGlnisLeuCysGlyerisLeuValGluAlaLeuTyrLeuValCysGlyGluArgGlyPhePheTyrThrProLysAla (insulin) 23B.9 23B.5.1 2 Gly Ala 4 3 Me 3 3 Me Me 3 Me GlyAla GlyGly AlaAla AlaGly GlyAla Gly Ala 22 22.3.2 t Boc 9Fmoc t 9 Me 3 C CMe 3 di-t-butyl dicarbonate (Boc 2 ) Cl 9 9fluorenylmethyl chloroformate GlyAla DCC 16
Et 3 2 C 2 t-bu -t-bu t-bu t-bu C 2 Boc 2 C 2 Boc C 2 Boc C 2 C Boc C 2 C BocC 2 C C dicyclohexylcarbodiimide (DCC) Boc BocC 2 C C 2 C 2 Me Me BocC 2 C C Me C C 2 Me Boc Me C C 2 Me C 2 Me 3 Cl Ac 3 Cl C 2 Me C 2 C 3 Cl C 2 Me a 2, Me 2 C 2 GlyAla 22.4 17
1960.B. Merrifield 1984 solid-phase peptide synthesis 23B.5.2 23B.10 C C 1 1 1 Fmoc C ClC 2 Fmoc C 2 2 C 2 1 2 C C 2 2 Fmoc C 2 DCC C 2 Cl 1 Fmoc 2 C C 2 C 2 Cl Fmoc 3 C 2 DCC Fmoc 3 2 1 C C 2 F 2 3 2 1 C 2 C 2 23B.10 18
C 2 Cl F F Merrifield automated solid-phase peptide synthesis 27 87128 4 17 369 99 23B.10 Boc Fmoc 23B.11 GlyLysAla Fmoc Fmoc FmocAla Fmoc Lys FmocGly 3 3 1980 DA sequence sequencing 19
23B.6.1 a 2 2,3 1,4 C C C C C 2 C 2 C C dithiothreitol (DTT) C 2 C 2 C C IC 2 C 2 2 C C 2 C C 2 C 2 23B.11 23B.12 2 2 vulcanization b 20
3 Cl (6 mol dm 3 ) 100 C, 24 h 23B.13 c Edman Edman degradation Ph C 2 phenyl isothiocyanate 1 3 2 1 3 Ph 2 Ph 1 3 2 Ph 1 3 2 2 1 1 3 Cl 2 2 3 Ph Ph 23B.12 Edman 21
d cyanogen bromide: BrC C BrC MeC Br Me C Me Br C Me C 3 Cl 3 3 Cl 3 23B.13 23B.3 2,4 2 2 2 F 2,4 2,4-dinitrofluorobenzene 1 (anger ) Ar ac 3 2 3 2 2 1 2 3 3 2 2 1 C 2 22
F. anger anger anger 1958 e protease peptidase trypsin chymotrypsin C elastase C C carboxypeptidase A B 2 B C C A 23B.2 23B.2 Edman Met C endopeptidase * Arg Lys C * C Tyr, Phe, Trp C Gly, Ala exopeptidase A C Arg Lys B C Arg Lys * Pro 23
23B.14 (a) GluArger (b) PheGlyAla 23B.15 GlyArgPheAlaLysAspTrpArgGluTyrValAla 23B.6.2 EI MALDI J.B. Fenn 2002 M M MM M M pmol: 10 12 mol 23B.6.3 23C primary structure 24
secondary structure tertiary structure 2 quaternary structure 23B.7.1 23B.4.1 C 23B.14 C C C C 23B.14 a βpleated sheet: 23B.15 23B.15 C parallelantiparallel 23B.16a 23B.16b 70 nm 7.0 25
(a) (b) C C C C C C 23B.16 (a) (b) βturn 23B.17a 23B.17b (a) 4 (b) 3 2 1 23B.17 (a) (b) 26
b 4 23B.18αhelix 3.6 1 54 nm 5.4 23B.18 c fibrous protein globular protein 2 27
23B.7.2 1 hydrophobic interaction non-covalent interaction 2 2.10 23B.1 23B.19 28
23B.19 Yikrazuul denaturation p 23B.7.3 50,000 2 2 2 23B.20 29
図 23B.20 ヘモグロビンの三次構造と四次構造 Zephyris at the English Wikipedia 問 題 23B.16 次のアミノ酸のうち 水溶液中で球状タンパク質の表面に存在する可能 性の高いものはどれか 理由とともに答えよ (a) Phe (b) er (c) Asp (d) Lys (e) Val (f) Gln まとめ ペ プ チ ド とタ ン パ ク 質 ポ リ ペ プ チ ド と総称する は αアミノ酸のポリマーで ある 天然のキラルな α ア ミ ノ 酸 は 通常 L 立体配置をもっており システイン以外は 配置に相当する αアミノ酸は p ７では双 性 イ オ ン になっており 側鎖に酸あるいは塩基官能基を もつものもある アミノ酸 あるいはペプチド の電荷をもたない形が最も多くなる p を等 電 点 と いう L αアミノ酸は 2オキソカルボン酸から脱水素酵素 水素化を触媒 による還元 的アミノ化あるいはアミノ基転移酵素によるアミノ基転移によって生合成される 30
α α trecker BIAP α C Boc Fmoc DCC Edman BrC Met C Arg Lys C Tyr, Phe, Trp C 1 van der Waals 31
23B.17 L, (a) (b) (c) 23B.18 p 2 p 11 (a) (b) (c) (d) 23B.19 p (a) p 0 (b) p 3 (c) p 7 (d) p 11 23B.20 23B.21 23B.22 p 6.0 (a) (b) (c) 23B.23 p 7 (a) GlyisAla (b) PheCysGlu 23B.24 Boc 23B.25 C 2 CC 2 C 2 Cl 32
23B.26 23B.12 Edman 23B.27 23B.3 anger 2,4 23B.28 (a) GlyArgPheAla (b) LysTrpIleArg 23B.29 Ala, Arg, Cys, Glu, Gly 2, is, Leu, Phe, Val Cys ValLeu GluPheGly GlyArgCys isgluphe LeuGlyAla Edman 23B.30 254 nm 395 nm 1(6 ) 2,5 2 CC 2 p 9 2 23B.31 (a) (b) (c) (d) (e) 33