R

Scheme B.26.1.

Scheme B.26.2.

located at the C- and N-termini of the peptide segments that need to be coupled. In Scheme B.26.1, X and Y represent an electrophile-nucleophile pair and Z the intermediate bond between the two peptide segments that originates after the capture reaction. Natural a-amino acids containing heteroatoms in their side-chains, e.g. Cys, Ser, Thr, His and Trp, can be used as N-terminal nucleophiles [1]. Typical C-terminal electrophiles include, e.g., O-glycoaldehyde esters and thioesters. In recent years a variety of peptide ligation methods has been developed; these differ in the nature of the elec-trophilic and nucleophilic groups involved in the chemoselective capture reaction [1].

A peptide ligation method that has attracted widespread attention is the so-called native chemical ligation (NCL) strategy introduced by Kent et al. (Scheme B.26.2) [2]. In NCL the thiol group of an N-terminal Cys residue acts as a nucleophile to attack the carbonyl carbon atom of a thioester moiety at the C-terminus of a second peptide segment. This results in the formation of a thioester intermediate which undergoes rapid intramolecular S,N-acyl migration to generate a peptide bond. This method has been successfully applied to the total chemical synthesis of the 72-amino acid protein interleukin 8 (IL-8) [2]. After purification, the correctly folded protein with properties identical with those of an authentic IL-8 sample was obtained.

1 (a) P. E. Dawson, S. B. H. Kent, Annu. Rev. Biochem. 2000, 69, 923-960; (b) J. A. Borgia, G. B. Fields, Trends Biotechnol. 2000, 18, 243-251; (c) J. P. Tam, J. Xu,

K. D. Eom, Biopolymers (Peptide Sci.) 2001, 60, 194-205. 2 P. E. Dawson, T. W. Muir, I. Clark-Lewis, S. B. H. Kent, Science 1994, 266, 776-779.

Index a absorption and emission spectroscopy 172, 176

acceptor-donor-acceptor pattern 156 acetylcholine 125, 137 acridizinium 184 acridizinium derivatives 176 ff acyl acceptor and donor 390 f acyl-4-amidino and -4-guanidinophenyl esters

(OGp) 391 acetylation 440 active transport 63, 79, 137 f adenosine 253

adenosine triphosphate ATP 527 S-adenosyl methionine (SAM) 94 f affinity 130, 221 affinity chromatography 249, 435 aggregation 160 aging 364 albothricin 70 alkaline-phosphatase 211 alkaloids 63, 70, 79 allosteric effect 204 allylic 1,2-interaction 22 allylic alkylations 438 Alzheimer 148, 155 f, 192, 262 amino acids see also peptides 63, 135, 140, 209, 389, 392, 502

- «-amino acid N-carboxyanhydrides 541

- Leuch's anhydrides 541

- non-proteinogenic amino acid 63 ff, 389 «-amino acids 68, 541 f, 545 f,548

- aspartic acid 266, 276

- diamino acids 209

- glutamic acid 126

- hydroxyproline 134 f

- racemization 163 j-amino acids 63 ff

- jS-amino-i-alanine 74

- j-aminoisobutyric acid 64, 93

- aminomutases 93

- j-arginine 69

- biosynthesis 90 ff

- cispentacin 79

- j-glutamate 69

- ¿-hydroxylations 75

- isoserine 67

- j-leucine 69

- jS-lysine 69

- nomenclature 65, 66 f,76 f,83

- b-tyrosine 67, 70 ff, 99 a-amino acid coupling 554 9-aminoacridizinium bromide 176 3-aminobenzoic acid 126 ff aminocarbasugars 516 f aminoglycosides 69 f aminomethylanthracene 441 f aminomutases 93 ff

- reaction mechanism 94 6-aminopicolinic acid 132 aminopyrazole 156 ff amphiphilic molecules 544 amyloid-j-peptide (Aj) 147, 155 amyloid precursor protein (APP) 147, 167,

262 f, 264 anion complexation 129 f anion recognition 131f anisotropy differences 313 anthracene 423 f antibacterial 80 antifungal 80 antioxidant 197

aptamers 249 ff a-i arabinose 120 arrays 485 ff

- cell arrays 492

- DNA arrays 485 f

- protein arrays 487 f

- small molecule arrays 493 f artificial lectin ligands 203 ff artificial molecular motors 537 artificial molecular rotary motors 526 artificial nucleobase 379

artificial receptors 109 ff, 124 ff, 140 ff, 155 ff, 218 f aryl diynes 237 aspartic protease 262 ff, 276 f association constant = Ka value see also dissociation constant, binding constant, IC50 112, 117, 143, 146, 151, 158 f,162, 177

asialoglycoprotein receptor (ASGPR) 207

asthma 227 ff

ATP 527 ff

ATP synthesis 527

automated synthesizer 243

automation 437, 485

aza-Diels-Alder reaction 23

b bacteria 63 ff bacterial and viral infections 109 bacteriophage T7 333 f ^-barrels 137, 139 bathochromic shift 176 bestatin 285

binding constant 144, 146, 150, 178, 212 binding energy 154 binding motifs 109 binding pocket 302

binding selectivity 124 f, 140 f, 155 f, 203 f,

217 f, 235 f,252 f, 262 f,293 f, 317, 396 binding site 120, 178 BINOL 112 f, 117 biotechnological production 501 ff biotin 211, 345 f, 425 ff, 492 boronic acid 109 bryostatin 53 building block 278

CaaX-box 218, 220 calixarenes 126 f cancer 311, 352, 423 cancer metastasis 203 cancer therapeutics 219

carbasugars 518 carbohydrate 49, 109 ff, 203 ff carbohydrate binding proteins 120, 203 ff carbohydrate recognition 109 ff, 119 ff, 203 ff

- enthalpy 204

- entropy 204 multivalency 203 f,212 f carbohydrate-lectin interactions 119 ff, 203 ff carboxylate binding 143 ff carboxymethyl thioesters 392 carboxypeptidase A 131 f, 141 f carcinogenesis 364, 369, 379

Caro's acid 283

catalysis see also enzymes 423

- biocatalysts 501 ff

- discovery of catalysts 436 ff

- fermentation 501 ff

- proteases 389 ff

- ribozymes 404 ff, 422 ff catalyst discovery 436 ff, 508 catalytic triad 239, 397 catalytic turnover 429 catechol units 40 catenanes 526, 530

- protein[2]catenane 550, 552 cation-re interaction 126, 146 cation recognition 124 f

CD spectroscopy 26 f,176 f, 253, 255, 531 cell-cell communication 203 cell-surface engineering 57 ceramide 48 chaotrophic anions 26 chaperones 169

charge transfer in DNA 172, 369 ff chemical enzyme modifications 396

chip technology see microarrays 379, 485 ff cholera toxin 50

chorismate 512 ff chymotrypsin 240, 392, 394, 396

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