Cell penetrating peptide (CPP)-conjugated desferrioxamine for enhanced neuroprotection: Synthesis and in vitro evaluation

Bioconjugate Chemistry

Volumn 25, Issue 11, 2014, Pages 2067-2080

  Goswami, Dibakar ^a   Machini, M Teresa ^a   Silvestre, Daniel M ^a   Nomura, Cassiana S ^a   Esposito, Breno Pannia ^a  

^a UNIVERSITY OF SÃO PAULO   (Brazil)

Author keywords

[No Author keywords available]

Indexed keywords

BINDING ENERGY; BIOCHEMISTRY; CELL CULTURE; IRON COMPOUNDS; LANTHANUM COMPOUNDS; PEPTIDES;

CELL-PENETRATING PEPTIDE; DELIVERY VECTOR; DESFERRIOXAMINE; IN-VITRO EVALUATION; IRON OVERLOADS; IRREVERSIBLE DAMAGE; LABILE IRONS; NEUROPROTECTION; REACTIVE OXYGEN SPECIES; SIDEROPHORES;

REDOX REACTIONS;

APOTRANSFERRIN; CALCEIN; CELL PENETRATING PEPTIDE; DEFEROXAMINE; FLUORESCEIN; IRON COMPLEX; NEUROPROTECTIVE AGENT; PENETRATIN; SIDEROPHORE; TAT(47-57) PEPTIDE; UNCLASSIFIED DRUG; ANTIOXIDANT; APOPROTEIN; DRUG CARRIER; FLUORESCEIN DERIVATIVE; IRON; TRANSACTIVATOR PROTEIN; TRANSFERRIN;

ANTIOXIDANT ACTIVITY; ARTICLE; CHEMICAL STRUCTURE; DRUG BIOAVAILABILITY; DRUG CONJUGATION; DRUG DELIVERY SYSTEM; DRUG PENETRATION; DRUG SCREENING; DRUG SYNTHESIS; HELA CELL LINE; IN VITRO STUDY; IRON BLOOD LEVEL; IRON OVERLOAD; NEUROPROTECTION; AMINO ACID SEQUENCE; BINDING COMPETITION; CHEMISTRY; HUMAN; METABOLISM; MOLECULAR GENETICS; PERMEABILITY; SYNTHESIS;

AMINO ACID SEQUENCE; ANTIOXIDANTS; APOPROTEINS; BINDING, COMPETITIVE; CELL-PENETRATING PEPTIDES; CHEMISTRY TECHNIQUES, SYNTHETIC; DEFEROXAMINE; DRUG CARRIERS; FLUORESCEIN; FLUORESCEINS; GENE PRODUCTS, TAT; HELA CELLS; HUMANS; IRON; MOLECULAR SEQUENCE DATA; NEUROPROTECTIVE AGENTS; PERMEABILITY; TRANSFERRIN;

EID: 84913538203     PISSN: 10431802     EISSN: 15204812     Source Type: Journal    
DOI: 10.1021/bc5004197     Document Type: Article

References (110)

1. McDowell, L. R. (2003) Iron. Minerals in Animal And Human Nutrition, 2 nd ed., pp 203-233, Chapter 7, Elsevier Science, Amsterdam.
2. Abbaspour, N., Hurrell, R., and Kelishadi, R. (2014) Review on iron and its importance for human health J. Res. Med. Sci. 19, 164-174
3. Piperno, A. (1998) Classification and diagnosis of iron overload Haematologica 83, 447-455
4. Breuer, W., Epsztejn, S., and Cabantchik, Z. I. (1996) Dynamics of the cytosolic chelatable iron pool of K562 cells FEBS Lett. 382, 304-308
5. Cabantchik, Z. I., Breuer, W., Zanninelli, G., and Cianciulli, P. (2005) LPI-labile plasma iron in iron overload Best Pract. Res., Clin. Haematol. 18, 277-287
6. Halliwell, B. and Gutteridge, J. M. C. (1989) Free Radicals in Biology and Medicine, 2 nd ed., pp 63, Oxford University Press, Oxford.
7. Aisen, P., Enns, C., and Wessling-Resnick, M. (2001) Chemistry and biology of eukaryotic iron metabolism Int. J. Biochem. Cell B 33, 940-959
8. Sebastiani, G. and Pantopoulos, K. (2011) Disorders associated with systemic or local iron overload: from pathophysiology to clinical practice Metallomics 3, 971-986
9. Fleming, R. E. and Ponka, P. (2012) Mechanisms of disease: iron overload in human disease N. Engl. J. Med. 366, 348-59
10. Barnham, K. J., Masters, C. L., and Bush, A. I. (2004) Neurodegenerative diseases and oxidative stress Nat. Rev. Drug Discovery 3, 205-214
11. Zecca, L., Youdim, M. B. H., Riederer, P., Connor, J. R., and Crichton, R. R. (2004) Iron, brain ageing and neurodegenerative disorders Nat. Rev. Neurosci. 5, 863-873
12. Halliwell, B. (2006) Oxidative stress and neurodegeneration: where are we now? J. Neurochem. 97, 1634-1658
13. Piloni, N. E., Fermandez, V., Videla, L. A., and Puntarulo, S. (2013) Acute iron overload and oxidative stress in brain Toxicology 314, 174-182
14. Raven, E. P., Lu, P. H., Heydari, T. A. P., and Bartzokis, G. (2013) Increased iron levels and decreased tissue integrity in hippocampus of Alzheimer's disease detected in vivo with magnetic resonance imaging J. Alzheimer's Dis. 37, 127-136
15. Bartzokis, G., Cummings, J. L., Markham, C. H., Marmarelis, P. Z., Treciokas, L. J., Tishler, T. A., Marder, S. R., and Mintz, J. (1999) MRI evaluation of brain iron in earlier- and later-onset Parkinson's disease and normal subjects Magn. Reson. Imaging 17, 213-222
16. Hadzhieva, M., Kirches, E., and Mawrin, C. (2014) Review: Iron metabolism and the role of iron in neurodegenerative disorders Neuropathol. Appl. Neurobiol. 40, 240-257
17. Bartzokis, G. and Tishler, T. A. (2000) MRI evaluation of basal ganglia ferritin iron and eurotoxicity in Alzheimer's and Huntingon's disease Cell Mol. Biol. 46, 821-833
18. Bartzokis, G., Lu, P. H., Tingus, K., Peters, D. G., Amar, C. P., Tishler, T. A., Finn, J. P., Villablanca, P., Altshuler, L. L., Mintz, J., Neely, E., and Connor, J. R. (2011) Gender and iron genes may modify associations between brain iron and memory in healthy aging Neuropsychopharmacology 36, 1375-1384
19. Bondy, S. C., Guo-Ross, S. X., and Truong, A. T. (1998) Promotion of transition metal-induced reactive oxygen species formation by β-amyloid Brain Res. 799, 91-96
20. Lovell, M. A., Robertson, J. D., Teesdale, W. J., Campbell, J. L., and Markesbery, W. R. (1998) Copper, iron and zinc in Alzheimer's disease senile plaques J. Neurol. Sci. 158, 47-52
21. Bush, A. I., Pettingell, W. H., Multhaup, G., Paradis, M. D., Vonsattel, J. P., Gusella, J. F., Beyreuther, K., Masters, C. L., and Tanzi, R. E. (1994) Rapid induction of Alzheimer A beta amyloid formation by zinc Science 265, 1464-1467
22. Liu, G., Men, P., Perry, G., and Smith, M. A. (2010) Nanoparticle and iron chelators as a potential novel Alzheimer therapy Methods Mol. Biol. 610, 123-144
23. Kalinowski, D. S. and Richardson, D. R. (2005) The evolution of iron chelators for the treatment of iron overload disease and cancer Pharmacol. Rev. 57, 547-583
24. Dixon, S. J. and Stockwell, B. R. (2014) The role of iron and reactive oxygen species in cell death Nat. Chem. Biol. 10, 9-17
25. Hider, R. C. and Hall, A. D. (1991) 2 clinically useful chelators of tripositive elements Prog. Med. Chem. 28, 41-173
26. Bendova, P., Mackova, E., Haskova, P., Vavrova, A., Jirkovsky, E., Sterba, M., Popelova, O., Kalinowski, D. S., Kovarikova, P., Vavrova, K., Richardson, D. R., and Simunek, T. (2010) Comparison of clinically used and experimental iron chelators for protection against oxidative stress-induced cellular injury Chem. Res. Toxicol. 23, 1105-1114
27. Aouad, F., Florence, A., Zhang, Y., Collins, F., Henry, C., Ward, R. J., and Crichton, R. R. (2002) Evaluation of new iron chelators and their therapeutic potential Inorg. Chim. Acta 339, 470-480
28. Brittenham, G. M. (2003) Iron chelators and iron toxicity Alcohol 30, 151-158
29. Olivieri, N. F. and Brittenham, G. M. (1997) Iron-chelating therapy and the treatment of thalassemia Blood 89, 739-761
30. Blatt, J. and Stitely, S. (1987) Antineuroblastoma activity of desferoxamine in human cell lines Cancer Res. 47, 1749-1750
31. Sharma, R. N. and Pancholi, S. S. (2010) Oral iron chelators: a new avenue for the management of thalassemia major J. Curr. Pharm. Res. 1, 1-7, and the references cited therein.
32. McLachlan, D. R., Kruck, T. P., Lukiw, W. J., and Krishnan, S. S. (1991) Would decreased aluminum ingestion reduce the incidence of Alzheimer's disease? Can. Med. Assoc. J. 145, 793-804
33. Lynch, S. G., Fonseca, T., and Levine, S. (2000) A multiple course trial of desferrioxamine in chronic progressive multiple sclerosis Cell Mol. Biol. 46, 865-869
34. Liu, G., Men, P., Perry, G., and Smith, M. A. (2009) Chapter 5-Development of iron chelator-nanoparticle conjugates as potential therapeutic agents for Alzheimer disease Prog. Brain Res. 180, 97-108
35. Liu, X. S., Patterson, L. D., Miller, M. J., and Theil, E. C. (2007) Peptides selected for the protein nanocage pores change the rate of iron recovery from the ferritin mineral J. Biol. Chem. 282, 31821-31825
36. Moggia, F., Brisset, H., Fages, F., Chaix, C., Mandrand, B., Dias, M., and Levillain, E. (2006) Design, synthesis and redox properties of two ferrocene-containing iron chelators Tetrahedron Lett. 47, 3371-3374
37. Loyevsky, M., Lytton, S. D., Mester, B., Libman, J., Shanzer, A., and Cabantchik, Z. I. (1993) The antimalarial action of Desferal involves a direct access route to erythrocytic (Plasmodium falciparum) parasites J. Clin. Invest. 91, 218-224
38. Palanch-e, T., Marmolle, F., Abdallah, M. A., Shanzer, A., and Albrecht-Gary, A.-M. (1999) Fluorescent siderophore-based chemosensors: iron(III) quantitiative determinations J. Biol. Inorg. Chem. 4, 188-198
39. Ghosh, M., Lambert, L. J., Huber, P. W., and Miller, M. J. (1995) Synthesis, bioactivity, and DNA-cleaving ability of Desferrioxamine B-nalidixic acid and Anthraquinone carboxylic acid conjugates Bioorg. Med. Chem. Lett. 5, 2337-2340
40. 1H NMR study of four Desferrioxamine B derivatives and their ferric complexes J. Am. Chem. Soc. 116, 840-846
41. Rodgers, S. J. and Raymond, K. N. (1983) Ferric ion sequestering agents. 11. Synthesis and kinetics of iron removal from transferrin of catechoyl derivatives of Desferrioxamine B J. Med. Chem. 26, 439-442
42. White, D. L., Durbin, P. W., Jeung, N., and Raymond, K. N. (1988) Specific sequestering agents from the actinites. 16. Synthesis and initial biological testing of polydentate Oxohydroxypyridinecarboxylate ligands J. Med. Chem. 31, 11-18
43. Liu, J., Obando, D., Schipanski, L. G., Groebler, L. K., Witting, P. K., Kalinowski, D. S., Richardson, D. R., and Codd, R. (2010) Conjugates of Desferrioxamine B (DFOB) with derivatives of adamantane or with orally available chelators as potential agents for treating iron overload J. Med. Chem. 53, 1370-1382
44. Liddell, J. R., Obando, D., Liu, J., Ganio, G., Volitakis, I., Mok, S. S., Crouch, P. J., White, A. R., and Codd, R. (2013) Lipophilic adamantyl- or deferasirox-based conjugates of desferrioxamine B have enhanced neuroprotective capacity: implications for Parkinson disease Free Radic. Biol. Med. 60, 147-156
45. Dragsten, P. R., Hallaway, P. E., Hanson, G. J., Berger, A. E., Bernard, B., and Hedlund, B. E. (2000) First human studies with a high-molecular-weight iron chelator J. Lab. Clin. Med. 135, 57-65
46. Poreddy, A. R., Schall, O. F., Osiek, T. A., Wheatley, J. R., Beusen, D. D., Marshall, G. R., and Slomczynska, U. (2004) Hydroxamate-based iron chelators: combinatorial syntheses of desferrioxamine B analogues and evaluation of binding affinities J. Comb. Chem. 6, 239-254
47. Huang, X., Moir, R. D., Tanzi, R. E., Bush, A. I., and Rogers, J. T. (2004) Redox-active metals, oxidative stress, and Alzheimer's disease pathology Ann. N.Y. Acad. Sci. 1012, 153-163
48. Amit, T., Avramovich-Tirosh, Y., Youdim, M. B. H., and Mandel, S. (2008) Targeting multiple Alzheimer's disease etiologies with multimodal neuroprotective and neurorestorative iron chelators FASEB J. 22, 1296-1305
49. Wang, Y., Branicky, R., Stepanyan, Z., Carroll, M., Guimond, M.-P., Hihi, A., Hayes, S., McBride, K., and Hekimi, S. (2009) The anti-neurodegeneration drug clioquinol inhibits the aging-associated protein CLK-1 J. Biol. Chem. 284, 314-323
50. Yuan, J., Loveyoy, D. B., and Richardson, D. R. (2004) Novel di-2-pyridyl-derived iron chelators with marked and selective antitumor activity: in vitro and in vivo assessment Blood 104, 1450-1458
51. Scott, L. E. and Orvig, C. (2009) Medicinal inorganic chemistry approaches to passivation and removal of aberrant metal ions in disease Chem. Rev. 109, 4885-4910
52. Youdim, M. B. H., Fridkin, M., and Zheng, H. (2004) Novel bifunctional drugs targeting monoamine oxidase inhibition and iron chelation as an approach to neuroprotection in Parkinson's disease and other neurodegenerative diseases J. Neural Transm. Suppl. 71, 163-172
53. Perez, C. A., Tong, Y., and Guo, M. (2008) Iron chelators as potential therapeutic agents for Parkinsons disease Curr. Bioact. Compd. 4, 150-158
54. Liu, Z. D. and Hider, R. C. (2002) Iron chelator chemistry. In Molecular and Cellular Iron Transport (Templeton, D., Ed.) p 360, CRC Press, New York.
55. Hider, R. C., Porter, J. B., and Singh, S. (1994) The design of therapeutically useful iron chelators. In The development of iron chelators for clinical use (Bergeron, R. J. and Brittenham, G. M., Eds.) pp 353-371, CRC Press, Boca Raton.
56. Copolovici, D. M., Langel, K., Eriste, E., and Langel, Ü. (2014) Cell-penetrating peptides: design, synthesis, and applications ACS Nano 8, 1972-1994
57. Brooks, H., Lebleu, B., and Vives, E. (2005) Tat peptide-mediated cellular delivery: back to basics Adv. Drug Delivery Rev. 57, 559-577
58. Majumdar, S. and Siahaan, T. J. (2012) Peptide-mediated targeted drug delivery Med. Res. Rev. 32, 637-658
59. Wang, F., Wang, Y., Zhang, X., Zhang, W., Guo, S., and Jin, F. (2014) Recent progress of cell-penetrating peptides as new carriers for intracellular cargo delivery J. Controlled Release 174, 126-136
60. León-Rodríguez, L. M. D. and Kovacs, Z. (2008) The synthesis and chelation chemistry of DOTA-peptide conjugates Bioconjugate Chem. 19, 391-402
61. Heitz, F., Morris, M. C., and Divita, G. (2009) Twenty years of cell-penetrating peptides: from molecular mechanisms to therapeutics Br. J. Pharmacol. 157, 195-206
62. Frankel, A. D. and Pabo, C. O. (1988) Cellular uptake of the Tat protein from human immunodeficiency virus Cell 55, 1189-1193
63. Green, M. and Loewenstein, P. M. (1988) Autonomous functional domains of chemically synthesized human immunodeficiency virus Tat trans-activator protein Cell 55, 1179-1188
64. Derossi, D., Joliot, A. H., Chassaing, G., and Prochiantz, A. (1994) The third helix of the Antennapedia homeodomain translocates through biological membranes J. Biol. Chem. 269, 10444-10450
65. Schwarze, S. R., Ho, A., Vocero-Akbani, A., and Dowdy, S. F. (1999) In vivo protein transduction: delivery of a biologically active protein into the mouse Science 285, 1569-1572
66. Qin, Y., Chen, H., Yuan, W., Kuai, R., Zhang, Q., Xie, F., Zhang, L., Zhang, Z., Liu, J., and He, Q. (2011) Liposome formulated with TAT- modified cholesterol for enhancing the brain delivery Int. J. Pharm. 419, 85-95
67. Liu, L., Venkatraman, S. S., Yang, Y.-Y., Guo, K., Lu, J., He, B., Moochhala, S., and Kan, L. (2008) Polymeric micelles anchored with TAT for delivery of antibiotics across the blood-brain barrier Biopolymers 90, 617-23
68. Wadia, J. S., Stan, R. V., and Dowdy, S. F. (2004) Transducible TAT-HA fusogenic peptide enhances escape of TAT-fusion proteins after lipid raft macropinocytosis Nat. Med. 10, 310-315
69. Torchilin, V. P., Rammohan, R., Weissig, V., and Levchenko, T. S. (2001) TAT peptide on the surface of liposomes affords their efficient intracellular delivery even at low temperature and in the presence of metabolic inhibitors Proc. Natl. Acad. Sci. U. S. A. 98, 8786-8791
70. Dupont, E., Prochiantz, A., and Joliot, A. (2006) Penetratins. In Handbook of cell penetrating peptides, 2 nd ed. (Langel, Ü., Ed.) pp 5-28, CRC Press, Boca Raton.
71. Rousselle, C., Clair, P., Lefauconnier, J. M., Kaczorek, M., Scherrmann, J. M., and Temsamani, J. (2000) New advances in the transport of doxorubicin through the blood-brain barrier by a peptide vector-mediated strategy Mol. Pharmacol. 57, 679-686
72. Bolton, S. J., Jones, D. N., Darker, J. G., Eggleston, D. S., Hunter, A. J., and Walsh, F. S. (2000) Cellular uptake and spread of the cell-permeable peptide penetratin in adult rat brain Eur. J. Neurosci. 12, 2847-2855
73. Souza, M. P., Tavares, M. F. M., and Miranda, M. T. M. (2004) Racemization in stepwise solid-phase synthesis at elevated temperatures Tetrahedron 60, 4671-4681
74. Remuzgo, C., Andrade, G. F. S., Temperini, M. L. A., and Miranda, M. T. M. (2009) Acanthoscurrin fragment 101-132: total synthesis at 60°C of a novel difficult sequence Biopolymers (Pept. Sci.) 92, 65-75
75. Loffredo, C., Assunção, N. A., Gerhardt, J., and Miranda, M. T. M. (2009) Microwave-assisted solid-phase peptide synthesis at 60°C: alternative conditions with low enantiomerization J. Pept. Sci. 15, 808-815
76. Kaiser, E., Colescott, R. L., Bossinger, C. D., and Cook, P. I. (1970) Color test of detection of free amino groups in the solid phase synthesis of peptides Anal. Biochem. 34, 595-598
77. Adapa, S., Huher, P., and Keller-Schierlein, W. (1982) Isolierung, strukturaufklarung und synthese von ferrioxamin H Helv. Chim. Acta 65, 1818-1824
78. Prelog, V. (1963) Iron-containing antibiotics and microbic growth factors Pure Appl. Chem. 6, 327-338
79. Kline, M. A. and Orvig, C. (1992) Complexation of iron with the orally active decorporation drug L1 (3-Hydroxy-1,2-dimethyl-4-pyridinone) Clin. Chem. 38, 562-565
80. Hsieh, H.-P., Wu, Y.-T., Chen, S.-T., and Wang, K.-T. (1999) Direct solid-phase synthesis of octreotide conjugates: precursors for use as tumor-targeted radiopharmaceuticals Bioorg. Med. Chem. 7, 1797-1803
81. Kiyota, S., Franzoni, L., Nicastro, G., Benedetti, A., Oyama, S. JR., Viviani, W., Gambarini, A. G., Spisni, A., and Miranda, M. T. (2003) Introduction of a chemical constraint in a short peptide derived from human acidic fibroblast growth factor licits mitogenic structural determinants J. Med. Chem. 46, 2325-2333
82. Thomas, F., Serratrice, G., Béguin, C., Aman, E. S., Pierre, J. L., Fontecave, M., and Laulhère, J. P. (1999) Calcein as a fluorescent probe for ferric iron: application to iron nutrition in plant cells J. Biol. Chem. 274, 13375-13383
83. Espósito, B. P., Epsztejn, S., Breuer, W., and Cabantchik, Z. I. (2002) A review of fluorescence methods for assessing labile iron in cells and biological fluids Anal. Biochem. 304, 1-18
84. Breuer, W., Epsztejn, S., and Cabantchik, Z. I. (1995) Iron acquired from transferrin by K562 cells Is delivered into a cytoplasmic pool of chelatable iron(II) J. Biol. Chem. 270, 24209-24215
85. 3+ Clin. Chem. 33, 405-407
86. Turcot, I., Stintzi, A., Xu, J., and Raymond, K. N. (2000) Fast biological iron chelators: kinetics of iron removal from human diferric transferrin by multidentate hydroxypyridonates J. Biol. Inorg. Chem. 5, 634-641
87. Breuer, W. and Cabantchik, Z. I. (2001) A fluorescence-based one-step assay for serum non-transferrin-bound iron Anal. Biochem. 299, 194-202
88. Espósito, B. P., Breuer, W., Sirankapracha, P., Hershko, C., and Cabantchik, Z. I. (2003) Labile plasma iron in iron overload: redox activity and susceptibility to chelation Blood 102, 2670-2677
89. Gomes, A., Fernandes, E., and Lima, J. L. F. C. (2005) Fluorescence probes used for detection of reactive oxygen species J. Biochem. Biophys. Methods. 65, 45-80, and the references cited therein
90. Wilhelm, I., Fazakas, C., and Krizbai, I. A. (2011) In vitro models of the blood- brain barrier Acta Neurobiol. Exp. 71, 113-128
91. Reichel, A., Abbot, N. J., and Begley, D. J. (2002) Evaluation of the RBE4 cell line to explore carrier-mediated drug delivery to the CNS via the L-system amino acid transporter at the blood-brain barrier J. Drug Targeting 10, 277-283
92. Rouault, T. A. (2013) Iron metabolism in the CNS: implications for neurodegenerative diseases Nat. Rev. Neurosci. 14, 551-564
93. Batista-Nascimento, L., Pimentel, C., Menezes, R. A., and Rodrigues-Pousada, C. (2012) Iron and neurodegeneration: from cellular homeostasis to disease Oxid. Med. Cell Longev. 128647 10.1155/2012/128647
94. Thompson, K. J., Shoham, S., and Connor, J. R. (2001) Iron and neurodegenerative disorders Brain Res. Bull. 55, 155-164
95. Johnson, R. M., Harrison, S. D., and Maclean, D. (2011) Therapeutic applications of cell-penetrating peptides Methods Mol. Biol. 683, 535-551
96. Shi, N.-Q., Gao, W., Xiang, B., and Qi, X.-R. (2012) Enhancing cellular uptake of activable cell-penetrating peptide-doxorubicin conjugate by enzymatic cleavage Int. J. Nanomedicine 7, 1613-1621
97. Lim, K. J., Sung, B. H., Shin, J. R., Lee, Y. W., Kim, D. J., Yang, K. S., and Kim, S. C. (2013) A cancer specific cell-penetrating peptide, BR2, for the efficient delivery of an scFv into cancer cells PLoS One 8, e66084
98. Wang, W., Nema, S., and Teagarden, D. (2010) Protein aggregation-pathways and influencing factors Int. J. Pharm. 390, 89-99
99. Pagel, K., Wagner, S. C., Samedov, K., vonBerlepsch, H., Böttcher, C., and Koksch, B. (2006) Random coils, β-sheet ribbons, and α-helical fibers: one peptide adopting three different secondary structures at will J. Am. Chem. Soc. 128, 2196-2197
100. Mahler, H.-C., Friess, W., Grauschopf, U., and Kiese, S. (2009) Protein aggregation: pathways, induction factors and analysis J. Pharm. Sci. 98, 2909-2934
101. Breuer, W., Ermers, M. J. J., Pootrakul, P., Abramov, A., Hershko, C., and Cabantchik, Z. I. (2001) Desferrioxamine-chelatable iron, a component of serum non-transferrin-bound iron, used for assessing chelation therapy Blood 97, 792-798
102. Pollack, S., Vanderhoff, G., and Lasky, F. (1977) Iron removal from transferrin-an experimental study Biochim. Biophys. Acta 497, 481-487
103. Kontoghiorghes, G. J. (2009) Prospects for introducing deferiprone as potent pharmaceutical antioxidant Front. Biosci. (Elite Ed) 1, 161-178
104. Mishra, A., Lai, G. H., Schmidt, N. W., Sun, V. Z., Rodriguez, A. R., Tong, R., Tang, L., Cheng, J., Deming, T. J., Kamei, D. T., and Wong, G. C. L. (2011) Translocation of HIV TAT peptide and analogues induced by multiplexed membrane and cytoskeletal interactions Proc. Natl. Acad. Sci. U.S.A. 108, 16883-16888
105. Derossi, D., Calvet, S., Trembleau, A., Brunissen, A., Chassaing, G., and Prochiantz, A. (1996) Cell internalization of the third helix of the Antennapedia homeodomain is receptor-independent J. Biol. Chem. 271, 18188-18193
106. Fischer, P. M., Zhelev, N. Z., Wang, S., Melville, J. E., Fåhraeus, R., and Lane, D. P. (2000) Structure-activity relationship of truncated and substituted analogues of the intracellular delivery vector Penetratin J. Pept. Res. 55, 163-172
107. Berlose, J.-P., Convert, O., Derossi, D., Brunissen, A., and Chassaing, G. (1996) Conformational and associative behaviours of the third helix of Antennapedia homeodomain in membrane-mimetic environments Eur. J. Biochem. 242, 372-386
108. Prochiantz, A. (1996) Getting hydrophilic compounds into cells: lessons from homeopeptides Curr. Opin. Neurobiol. 6, 629-634
109. Thorén, P. E. G., Persson, D., Karlsson, M., and Nordén, B. (2000) The Antennapedia peptide penetratin translocates across lipid bilayers-the first direct observation FEBS Lett. 482, 265-268
110. Kamei, N., Morishita, M., Eda, Y., Ida, N., Nishio, R., and Takayama, K. (2008) Usefulness of cell-penetrating peptides to improve intestinal insulin absorption J. Controlled Release 132, 21-25, and references cited therein