crc press - E-Lib FK UWKS

More documents

Recommendations

Info

Interactions of Cell-Penetrating Peptides with Membranes 177 that showed that the monolayer uptake of these two peptides was governed by the hydrophobic domains. 48 This observation raised the following question: since both peptides bear the same hydrophilic sequence, how can the lipid headgroup-dependent uptake be governed by the hydrophobic domain? Some recent preliminary data suggest that the conformational state of this latter domain could be a determinant factor governing the membrane penetration of the shuttle peptides. Indeed, starting from the FP–NLS sequence, which is nonordered in water, several minor changes in the hydrophobic sequence lead to an α-helical peptide (peptide 6 of Table 8.2) that can penetrate indifferently into neutral and negatively charged model membranes. 8.3 CELLULAR INTERNALIZATION OF ANTENNAPEDIA This well-known shuttle peptide based on the third helix of Antennapedia, (R-Q-I-K- I-W-F-Q-N-R-R-M-K-W-K-K) can also reach the cytoplasm and is eventually conveyed to the nucleus of cells in culture through a pathway that does not involve classical receptor-mediated endocytosis. Several observations, such as that the peptide is not able to induce channel formation, together with the consequences of replacing the two tryptophan residues by phenylalanines that did not modify the helical structure but abolished translocation, led to proposal of a model implying inverted micelles (Figure 8.7). The main reasons for favoring this model are the limited size of the polypeptidic cargo and its conformation, the requirement of Trp residues, multimer formation, and formation of hexagonal phases or inverted micelles. 14,114 8.4 INTERNALIZATION VIA A VESICULAR PROCESS Vesicular internalization is suggested to be associated with self-assembly induced perturbation of the lipid bilayer. This can be illustrated by study of the mechanisms involved in translocation of human calcitonin (hCT) through excised bovine nasal mucosa. 23 Using two carboxyfluorescein-labeled hCT fragments, it was shown that, in presence of the endocytosis inhibitor cytochalasin D, mucosal-to-serosal and serosal-to-mucosal hCT permeabilities were equal. Pathway visualization by confocal laser scanning microscopy showed punctated fluorescence indicating vesicular internalization. In contrast, the N-terminal fragment lacking the beta-sheet forming C terminus was not internalized. Circular dichroism showed that, when interacting with neutral and negatively charged liposomes, hCT adopts beta-sheet conformation. In a concentrated aqueous solution, beta-sheet formation induces hCT self-assembly and fibrillation. It was proposed that the high lipid partitioning and beta-sheet formation result in C terminus-restricted supramolecular self-assembly in lipid membranes. Condensed hCT self-assemblies may explain the high capacity of net mucosal-to-serosal hCT permeation, which compares favorably with the low transport capacity of receptor-mediated endocytosis. 8.5 INTERNALIZATION VIA RECEPTOR One of the major problems in cancer chemotherapy is severe side effects that limit the dose of anticancer drugs because of their unselectivity for tumor vs. normal
178 Cell-Penetrating Peptides: Processes and Applications FIGURE 8.7 Model of internalization. In this model the peptide, arbitrarily represented as a dimer, recruits negatively charged phospholipids (filled circles) and induces the formation of an inverted micelle. The hydrophilic cavity of the micelle accommodates the peptide and, possibly, sequences attached to it can subsequently be released in the cytoplasmic compartment. (Adapted from Derossi, D. et al., J. Biol. Chem., 271, 18188, 1996. With permission.) cells. To this end, peptide–drug conjugates were designed to bind to specific receptors ex<strong>press</strong>ed on the tumor cells with subsequent internalization of the ligand–receptor complex. 22 Neuropeptide Y (NPY), a 36-amino acid peptide of the pancreatic polypeptide family, was chosen as model peptide because NPY receptors are overex<strong>press</strong>ed in a number of neuroblastoma tumors and their derived cell lines. Daunorubicin and doxorubicin, two widely used antineoplastic agents in tumor therapy, were covalently linked to NPY via two spacers that differ in stability.
Page 2 and 3:
CELL- PENETRATING PEPTIDES Processe
Page 4 and 5:
Pharmacology and Toxicology: Basic
Page 7 and 8:
Library of Congress Cataloging-in-P
Page 9 and 10:
to the handbook are prominent resea
Page 11 and 12:
REFERENCES 1. Green, M. and Loewens
Page 14 and 15:
Contributors Mats Andersson Microbi
Page 16 and 17:
Erin T. Pelkey Department of Chemis
Page 18 and 19:
Contents Section I Classes of Cell-
Page 20:
Chapter 16 Cell-Penetrating Peptide
Page 24 and 25:
1 CONTENTS 0-8493-1141-1/02/$0.00+$
Page 26 and 27:
The Tat-Derived Cell-Penetrating Pe
Page 28 and 29:
Page 30 and 31:
Page 32 and 33:
Page 34 and 35:
Page 36 and 37:
Page 38 and 39:
Page 40 and 41:
Page 42:
Page 45 and 46:
24 Cell-Penetrating Peptides: Proce
Page 47 and 48:
Page 49 and 50:
Page 51 and 52:
Page 53 and 54:
Page 55 and 56:
Page 57 and 58:
Page 59 and 60:
Page 61 and 62:
Page 63 and 64:
Page 65 and 66:
Page 67 and 68:
Page 69 and 70:
Page 71 and 72:
Page 74 and 75:
3 Transportans Margus Pooga, Mattia
Page 76 and 77:
Transportans 55 Indeed, galparan is
Page 78 and 79:
Transportans 57 especially the endo
Page 80 and 81:
Transportans 59 In the penetration
Page 82 and 83:
Transportans 61 A 21-mer antisense
Page 84 and 85:
Transportans 63 Commonly, the prote
Page 86 and 87:
Transportans 65 antibiotin antibodi
Page 88 and 89:
Transportans 67 For cross-linking o
Page 90 and 91:
Transportans 69 and still retain ef
Page 92 and 93:
4 CONTENTS 0-8493-1141-1/02/$0.00+$
Page 94 and 95:
Model Amphipathic Peptides 73 its D
Page 96 and 97:
Model Amphipathic Peptides 75 pmol/
Page 98 and 99:
TABLE 4.1 Internalization of Peptid
Page 100 and 101:
TABLE 4.2 Internalization of Peptid
Page 102 and 103:
Model Amphipathic Peptides 81 relat
Page 104 and 105:
Page 106 and 107:
Page 108 and 109:
Model Amphipathic Peptides 87 A cat
Page 110 and 111:
Model Amphipathic Peptides 89 At th
Page 112 and 113:
Model Amphipathic Peptides 91 16. H
Page 114 and 115:
5 CONTENTS 0-8493-1141-1/02/$0.00+$
Page 116 and 117:
Signal Sequence-Based Cell-Penetrat
Page 118 and 119:
Page 120 and 121:
Page 122 and 123:
Page 124 and 125:
Page 126 and 127:
Page 128 and 129:
Page 130 and 131:
Page 132 and 133:
Page 134:
Page 137 and 138:
116 Cell-Penetrating Peptides: Proc
Page 139 and 140:
Page 141 and 142:
Page 143 and 144:
Page 145 and 146:
Page 147 and 148: 126 Cell-Penetrating Peptides: Proc
Page 184 and 185: 8 CONTENTS 0-8493-1141-1/02/$0.00+$
Page 186 and 187: Interactions of Cell-Penetrating Pe
Page 208 and 209: 9 CONTENTS 0-8493-1141-1/02/$0.00+$
Page 210 and 211: Structure Prediction of CPPs and It
Page 228 and 229: FIGURE 9.7 (Color Figure 9.7 follow
Page 230 and 231: FIGURE 9.8 The center of the figure
Page 244 and 245: 10 CONTENTS 0-8493-1141-1/02/$0.00+
Page 246 and 247: Biophysical Studies of Cell-Penetra
Page 248 and 249:
Biophysical Studies of Cell-Penetra
Page 250 and 251:
Page 252 and 253:
Page 254 and 255:
Page 256 and 257:
Page 258 and 259:
Page 260 and 261:
Page 262 and 263:
Page 264 and 265:
Page 266 and 267:
11 CONTENTS 0-8493-1141-1/02/$0.00+
Page 268 and 269:
Toxicity and Side Effects of Cell-P
Page 270 and 271:
Page 272 and 273:
Page 274 and 275:
Page 276 and 277:
Page 278 and 279:
Page 280 and 281:
Page 282:
Page 285 and 286:
Page 287 and 288:
Page 289 and 290:
Page 291 and 292:
Page 293 and 294:
Page 295 and 296:
Page 298 and 299:
13 CONTENTS 0-8493-1141-1/02/$0.00+
Page 300 and 301:
Kinetics of Uptake of Cell-Penetrat
Page 302 and 303:
Page 304 and 305:
Page 306 and 307:
Page 308 and 309:
Page 310 and 311:
Page 312 and 313:
Page 314:
Page 317 and 318:
Page 319 and 320:
Page 321 and 322:
Page 323 and 324:
Page 325 and 326:
Page 327 and 328:
Page 329 and 330:
Page 331 and 332:
Page 333 and 334:
Page 335 and 336:
Page 337 and 338:
Page 339 and 340:
Page 341 and 342:
Page 343 and 344:
Page 345 and 346:
Page 348 and 349:
15 CONTENTS 0-8493-1141-1/02/$0.00+
Page 350 and 351:
Cell-Penetrating Peptide Conjugatio
Page 352 and 353:
Page 354 and 355:
Page 356 and 357:
Page 358 and 359:
Page 360 and 361:
Page 362 and 363:
FIGURE 15.9 (Color Figure 15.9 foll
Page 364 and 365:
Page 366 and 367:
Page 368 and 369:
16 CONTENTS 0-8493-1141-1/02/$0.00+
Page 370 and 371:
Cell-Penetrating Peptides as Vector
Page 372 and 373:
Page 374 and 375:
TABLE 16.1 Examples of Transport of
Page 376 and 377:
Page 378 and 379:
Page 380 and 381:
CPP 2 Cargo or mRNA CAP Antisense A
Page 382 and 383:
Page 384:
Page 387 and 388:
Page 389 and 390:
Page 391 and 392:
Page 393 and 394:
Page 395 and 396:
Page 398 and 399:
18 CONTENTS 0-8493-1141-1/02/$0.00+
Page 400 and 401:
Microbial Membrane-Permeating Pepti
Page 402 and 403:
Page 404 and 405:
Page 406 and 407:
Page 408 and 409:
Page 410 and 411:
Page 412 and 413:
Page 414 and 415:
Page 416 and 417:
Page 418 and 419:
Index A Abaecin, 129 Abz radiolabel
Page 420 and 421:
Index 399 Diffraction, 168 Disulphi
Page 422 and 423:
Index 401 structure prediction, 187
Page 424 and 425:
Index 403 pRB proteins, Tat-E1A bin
Page 426 and 427:
Index 405 lipid perturbation (secon
show all

crc press - E-Lib FK UWKS

Create successful ePaper yourself

Delete template?

Save as template?