Molecular umbrella-assisted transport of an oligonucleotide across cholesterol-rich phospholipid bilayers

Journal of the American Chemical Society

Volumn 127, Issue 45, 2005, Pages 15862-15870

  Janout, Vaclav ^a   Jing, Bingwen ^a   Regen, Steven L ^a  

^a LEHIGH UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CHOLESTEROL; DERIVATIVES; MATHEMATICAL MODELS; MEMBRANES; PHOSPHOLIPIDS; SYNTHESIS (CHEMICAL);

MEMBRANE TRANSPORT; MOITIES; UMBRELLA CONJUGATES; UMBRELLA-ASSISTED TRANSPORT;

OLIGOMERS;

1 PALMITOYL 2 OLEOYLGLYCERO 2 PHOSPHATIDYLGLYCEROL; 2 OLEOYL 1 PALMITOYLPHOSPHATIDYLCHOLINE; 5 MERCAPTO 2 NITROBENZOIC ACID; CHOLESTEROL; CHOLIC ACID; DEOXYCHOLIC ACID; LIPOSOME; LYSINE; NITROBENZOIC ACID DERIVATIVE; OLIGONUCLEOTIDE; PHOSPHATIDYLGLYCEROL; PHOSPHOLIPID; PHOSPHORYLCHOLINE; SPERMIDINE; UNCLASSIFIED DRUG;

AQUEOUS SOLUTION; ARTICLE; BINDING AFFINITY; CONJUGATE; DIFFUSION; LIPID BILAYER; MEMBRANE TRANSPORT; PARTITION COEFFICIENT; SYNTHESIS;

BIOLOGICAL TRANSPORT; CHOLESTEROL; CHOLIC ACID; DEOXYCHOLIC ACID; LIPID BILAYERS; LIPOSOMES; LYSINE; MODELS, MOLECULAR; NITROBENZOATES; OLIGONUCLEOTIDES; PHOSPHATIDYLCHOLINES; PHOSPHATIDYLGLYCEROLS; PHOSPHOLIPIDS; SPERMIDINE; STRUCTURE-ACTIVITY RELATIONSHIP; SULFHYDRYL COMPOUNDS;

EID: 27844556853     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja053930x     Document Type: Article

References (30)

1. Patil, S. D.; Rhodes, D. G.; Burgess, D. J. AAPS J. 2005, 7, E61-E75, Article 9 (http://www.aapsj.org).
2. Juliano, R. L.; Alahari, S.; Yoo, H.; Cho, M. Pharm. Res. 1999, 16, 494-502.
3. Dias, N.; Stein, C. A. Mol. Cancer Ther. 2002, 347-355.
4. Xu, D.; Kang, H.; Fisher, M.; Juliano, R. L. Mol. Pharmacol. 2004, 66, 268-275.
5. Chaltin, P.; Margineanu, A.; Marchand, D.; Aerschot, A. V.; Rozenski, J.; De Schryver, F.; Herrmann, A.; Mullen, K.; Juliano, R.; Fisher, M. H.; Kang, H.; De Feyeter, S.; Herdewijn, P. Bioconjugate Chem. 2005, 16, 827-836.
6. Fisher, A. A.; Ye, D.; Sergueev, D.; Fisher, M. H.; Shaw, B. R.; Juliano, R. L. J. Biol. Chem. 2002, 277, 22980-22984.
7. Weyermann, J.; Lochmann, D.; Zimmer, A. J. Controlled Release 2004, 100, 411-423.
8. Dass, C. R. Biotechnol. Appl. Biochem. 2004, 40, 113-122.
9. Vinogradov, S. V.; Batrakova, E. V.; Kabanov, A. V. Bioconjugate Chem. 2004, 15, 50-60.
10. Asokan, A.; Cho, M. J. Bioconjugate Chem. 2004, 15, 1166-1173.
11. Ye, Z.; Chen, K.; Guntake, R. V.; Mahoto, R. I. Biochemistry 2005, 44, 4466-4476.
12. Turner, J. J.; Arzumanov, A. A.; Gait, M. J. Nucleic Acids Res. 2005, 33, 27-42.
13. Santhakumaran, L. M.; Thomas, T.; Thomas, T. J. Nucleic Acids Res. 2004, 32, 2102-2112.
14. Rogers, F. A.; Manoharan, M.; Rabinovitch, P.; Ward, D. C.; Glazer, P. M. Nucleic Acids Res. 2004, 32, 6595-6604.
15. Matsumoto, T.; Numata, M.; Anada, T.; Mizu, M.; Koumoto, K.; Sakurai, K.; Nagasaki, T.; Shinkai, S. Biochim. Biophys. Acta 2004, 1670, 91-104.
16. Janout, V.; Jing, B.; Regen, S. L. Bioconjugate Chem. 2002, 13, 351-356.
17. Janout, V.; Staina, I. V.; Bandyopadhyay, P.; Regen, S. L. J. Am. Chem. Soc. 2001, 123, 9926-9927.
18. Gennis, R. B. Biomembranes: Molecular Structure and Function; Springer-Verlag: New York, 1989; Chapter 4.
19. (a) McConnell, H. M.; Radhakrishnan, A. Biochim. Biophys. Acta 2003, 1610, 159-173.
20. (b) Rubenstein, J. L. R.; Smith, B. A.; McConnell, H. M. Proc. Natl. Acad. Sci. U.S.A. 1979, 76, 15.
21. (c) Leathes, J. B. Lancet 1925, 208, 853-856.
22. Zhang, J.; Jing, B.; Regen, S. L. J. Am. Chem. Soc. 2003, 125, 13984.
23. Chen, W.; Shao, X.; Regen, S. L. J. Am. Chem. Soc. 2005, 127, 12727-12735.
24. A preliminary account of this work has previously appeared: Janout, V.; Regen, S. L. J. Am. Chem. Soc. 2005, 127, 22-23.
25. (a) Jing, B.; Janout, V.; Herold, B. C.; Klotman, M. E.; Heald, T.; Regen, S. L. J. Am. Chem. Soc. 2004, 126, 15930-15931.
26. (b) Bandyopadhyay, P.; Bandyopadhyay, P.; Regen, S. L. Bioconjugate Chem. 2002, 13, 1314.
27. Janout, V.; Zhang, L. H.; Staina, I. V.; DiGiorgio, C.; Regen, S. L. J. Am. Chem. Soc. 2001, 123, 9926-9927.
28. Boguslavsky, V.; Hruby, V. J.; O'Brien, D. F. J. Pept. Res. 2003, 61, 287-297.
29. Although it is clear that these molecular umbrella-oligonucleotide conjugates, and also ones that have been cleaved by entrapped glutathione. do not produce pores that allow for the passage of glutathione, we cannot rule out the possibility that smaller permeants may cross these membranes. The fact that a persulfated molecular umbrella, derived from eight choloyl groups, has been found to be nontoxic at concentrations as high as 1000 μg/mL does, however, offer significant encouragement that this molecular umbrella approach toward bilayer transport could be exploitable from a drug delivery standpoint. Detailed studies of the transport properties of these umbrellas are currently in progress.
30. 16 and 5-mercapto-2-nitrobenzoic acid. Thus, incubation of this conjugate with liposomes [POPC/POPG (95/5, mol/mol)] containing entrapped GSH, under experimental conditions that were similar to those used for 1, did not reveal a detectable USH (i.e., <2%) after 50 h. Evidence that this nonumbrella analogue was reactive toward GSH was also obtained by carrying out an additional experiment in which this conjugate (15 μM) was incubated with a vesicle dispersion that was 20 mg/mL in phospholipid and 71.4 μM in GSH. In this experiment, all of the GSH was present in the external aqueous phase; that is, the aqueous compartment of the vesicles contained only buffer. Analysis for USH showed a quantitative conversion after 2 h at 37 °C. The resulting dispersion was then subjected to the same dialysis conditions that were used in the transport experiment for 1. In this case, dialysis led to the complete removal of the oligonucleotide from the vesicles.