crc press - E-Lib FK UWKS

More documents

Recommendations

Info

Hydrophobic Membrane Translocating Sequence Peptides 131 The kFGF MTS, penetratin, and HIV-1 Tat peptides all fulfill these criteria and are currently regarded as the leading translocating peptide vectors. Whether prolinerich peptides will also meet all of these requirements remains to be determined, although results obtained to date are promising. Until a definitive study is performed in which the ability of different translocating peptides to transport the same cargo into cells is directly compared, the choice of peptide will largely be influenced by the types of uses described in the literature. The ultimate goal of our translocating peptide research is to design biologically active therapeutic compounds. For this, potentially three different segments must be included in a single compound: a targeting module, a penetrating module, and an effector module. The role of the targeting module would be to direct the attached penetrating and biologically active modules to specific cell types in vivo, e.g., cancer cells and virus-infected cells. One of the defining characterisitics of cancer cells is the overexpression of specific cell surface proteins 166-170 and this feature may be exploited in the design of anticancer agents. Effective antiviral agents may also be assembled where a biologically active antiviral drug such as a reverse transcriptase inhibitor can be linked to a cell-permeant peptide vector and targeted to infected cells. Virus-infected cells often express virusspecific proteins on the cell surface during replication; therefore, identification of a suitable target may be simplified. For example, human cytomegalovirus chemokine receptor US28 is expressed at the cell surface 171 and a number of HIV surface proteins are expressed prior to virion formation and budding. 172 Furthermore, this approach could be applied to development of a compound aimed at decreasing the multidrug resistance (MDR) exhibited by cancer cells. Many cancer types, including leukemia, multiple myeloma, lymphomas, and a variety of solid tumors, overexpress the cell surface protein P-glycoprotein (P-gp) that transports anticancer drugs out of cells before cytotoxic effects occur. 166 The administration of drugs capable of reversing this MDR is currently limited because of the toxic effect on normal tissues. The assembly of a molecule that can target and bind to the overexpressed P-gp protein, penetrate through the cell membrane, and deliver a chemotherapeutic agent to the cancer cell resulting in cell death is highly desirable. A major concern raised by Derossi et al. 9 is that the high efficiency of internalization exhibited by translocating peptides in vitro could have a detrimental effect on in vivo delivery because the peptide may be captured by cells at the delivery point and not reach target cells. Attachment of a targeting module addresses this concern to a certain extent. Ideally, the penetrating module would be completely masked by the targeting module and unavailable for nonspecific membrane interaction. Upon binding to the target receptor the target module would undergo a conformational change and expose the penetrating module to the lipid bilayer, thus allowing translocation to commence. In conclusion, the production of drugs and diagnostic tools involves not only the design of the empirical three-dimensional conformation of the biologically active component but also the rational design of an effective intracellular delivery system for subcellular activity. Hydrophobic MTS peptides have already proven their worth as peptide vectors through the delivery of peptides and proteins to the intracellular
132 Cell-Penetrating Peptides: Processes and Applications environment. We can now look beyond routine laboratory use of translocating peptides to development of effective agents for in vivo clinical and diagnostic use. REFERENCES 1. Wang. K., Feramisco, J.R., and Ash, J.F., Fluorescent localization of contractile proteins in tissue culture cells, Methods Enzymol., 85, 514, 1982. 2. Wang, Z. and Moran, M.F., Requirement for the adapter protein GRB2 in EGF receptor endocytosis, Science, 272, 1935, 1996. 3. Buday, L. and Downward, J., Epidermal growth factor regulates p21ras through the formation of a complex of receptor, Grb2 adapter protein, and Sos nucleotide exchange factor, Cell, 73, 611, 1993. 4. Giorgetti–Peraldi, S. et al., Cellular effects of phosphotyrosine-binding domain inhibitors on insulin receptor signaling and trafficking, Mol. Cell Biol., 17, 1180, 1997. 5. Fitzgerald, E.M. and Dolphin, A.C., Regulation of rat neuronal voltage-dependent calcium channels by endogenous p21-ras, Eur. J. Neurosci., 9, 1252, 1997. 6. Henkel, T. et al., Intramolecular masking of the nuclear location signal and dimerization domain in the precursor for the p50 NF-kappa B subunit, Cell, 68, 1121, 1992. 7. Perlmutter, R.M. and Alberola-Ila, J., The use of dominant-negative mutations to elucidate signal transduction pathways in lymphocytes, Curr. Opin. Immunol., 8, 285, 1996. 8. Schwarze, S.R. and Dowdy, S.F., In vivo protein transduction: intracellular delivery of biologically active proteins, compounds and DNA, Trends Pharmacol. Sci., 21, 45, 2000. 9. Derossi, D., Chassaing, G., and Prochiantz, A., Trojan peptides: the penetratin system for intracellular delivery, Trends Cell Biol., 8, 84, 1998. 10. Pooga, M. et al., Cell penetration by transportan, FASEB J., 12, 67, 1998. 11. Fujihara, S.M. and Nadler, S.G., Intranuclear targeted delivery of functional NFkappaB by 70 kDa heat shock protein, EMBO J., 18, 411, 1999. 12. Hawiger, J., Cellular import of functional peptides to block intracellular signaling, Curr. Opin. Immunol., 9, 189, 1997. 13. Elliott, G. and O’Hare, P., Intercellular trafficking and protein delivery by a herpesvirus structural protein, Cell, 88, 223, 1997. 14. Lundberg, M. and Johansson, M., Correspondence: is VP22 nuclear homing an artifact? Nat. Biotechnol., 19, 713, 2001. 15. O’Hare, P. and Elliott, G., Correspondence: is VP22 nuclear homing an artifact? Nat. Biotechnol., 19, 713, 2001. 16. Blobel, G. and Dobberstein, B., Transfer to proteins across membranes. II. Reconstitution of functional rough microsomes from heterologous components, J. Cell Biol., 67, 852, 1975. 17. Blobel, G., Intracellular protein topogenesis, Proc. Natl. Acad. Sci. U.S.A., 77, 1496, 1980. 18. Simon, S.M. and Blobel, G., Mechanisms of translocation of proteins across membranes, Subcell. Biochem., 21, 1, 1993. 19. von Heijne, G., Signal sequences. The limits of variation, J. Mol. Biol., 184, 99, 1985. 20. Briggs, M.S. and Gierasch, L.M., Molecular mechanisms of protein secretion: the role of the signal sequence, Adv. Protein Chem., 38, 109, 1986. 21. Gierasch, L.M., Signal sequences, Biochemistry, 28, 923, 1989. 22. von Heijne, G., The signal peptide, J. Membr. Biol., 115, 195, 1990.
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 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 134: Signal Sequence-Based Cell-Penetrat
Page 137 and 138: 116 Cell-Penetrating Peptides: Proc
Page 151: 130 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 202 and 203:
Interactions of Cell-Penetrating Pe
Page 204 and 205:
Page 206 and 207:
Page 208 and 209:
9 CONTENTS 0-8493-1141-1/02/$0.00+$
Page 210 and 211:
Structure Prediction of CPPs and It
Page 212 and 213:
Page 214 and 215:
Page 216 and 217:
Page 218 and 219:
Page 220 and 221:
Page 222 and 223:
Page 224 and 225:
Page 226 and 227:
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 232 and 233:
Page 234 and 235:
Page 236 and 237:
Page 238 and 239:
Page 240 and 241:
Page 242 and 243:
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:
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:
264 Cell-Penetrating Peptides: Proc
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

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?