Citation: Xiao-Feng Wang, Xian-Tao Yang, Yue Chen, Yang Liu, Lang Zou, Zhen-Jun Yang, Li-He Zhang. Solid phase synthesis of peptide-siRNA conjugates containing disulfide bond unit[J]. Chinese Chemical Letters, ;2013, 24(10): 873-876. shu

Solid phase synthesis of peptide-siRNA conjugates containing disulfide bond unit

1.
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China

Corresponding author: Zhen-Jun Yang,
Received Date: 8 April 2013
Available Online: 28 May 2013
Fund Project:

A disulfide-modified nucleoside was designed and synthesized. After loading the modified nucleoside on controlled pore glass (CPG), solid phase synthesis strategy was used to prepare peptide-oligonucleotide conjugates (N-3') containing disulfide bond unit. The 3'-sense strand peptide-siRNA conjugate (Ⅶ) maintained good gene silencing activity, while that of the 3'-antisense strand conjugate decreased somewhat. And the sense strand off-target effect of Ⅶ decreased remarkably.
- siRNA,
- Solid synthesis,
- Disulfide bond,
- Peptide,
- Conjugate
1. [1]
  [1] A. de Fougerolles, H.P. Vornlocher, J. Maraganore, J. Lieberman, Interfering with disease: a progress report on siRNA-based therapeutics, Nat. Rev. Drug Discov. 6 (2007) 443-453.
2. [2]
  [2] S. Zhang, B. Zhao, H. Jiang, B. Wang, B. Ma, Cationic lipids and polymers mediated vectors for delivery of siRNA, J. Control. Release 123 (2007) 1-10.
3. [3]
  [3] M. Morille, C. Passirani, A. Vonarbourg, A. Clavreul, J.P. Benoit, Progress in developing cationic vectors for non-viral systemic gene therapy against cancer, Biomaterials 29 (2008) 3477-3496.
4. [4]
  [4] J.D. Heidel, Z. Yu, J.Y. Liu, et al., Administration in non-human primates of escalating intravenous doses of targeted nanoparticles containing ribonucleotide reductase subunitM2 siRNA, Proc. Natl. Acad. Sci. U.S.A. 104 (2007) 5715-5721.
5. [5]
  [5] E. Song, P. Zhu, S.K. Lee, et al., Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptors, Nat. Biotechnol. 23 (2005) 709-717.
6. [6]
  [6] K.M. Stewart, K.L. Horton, S.O. Kelley, Cell-penetrating peptides as delivery vehicles for biology and medicine, Org. Biomol. Chem. 6 (2008) 2242-2255.
7. [7]
  [7] T. Endoh, T. Ohtsuki, Cellular siRNA delivery using cell-penetrating peptides modified for endosomal escape, Adv. Drug Deliv. Rev. 61 (2009) 704-709.
8. [8]
  [8] (a) A. Muratovska, M.R. Eccles, Conjugate for efficient delivery of short interfering RNA (siRNA) into mammalian cells, FEBS Lett. 558 (2004) 63-68;
9. [9]
  (b) Y.L. Chiu, A. Ali, C.Y. Chu, H. Cao, T.M. Rana, Visualizing a correlation between siRNA localization, cellular uptake, and RNAi in living cells, Chem. Biol. 11 (2004) 1165-1175;
10. [10]
  (c) T.J. Davidson, S. Harel, V.A. Arboleda, et al., Highly efficient small interfering RNA delivery to primary mammalian neurons induces MicroRNA-like effects before mRNA degradation, J. Neurosci. 24 (2004) 10040-10046.
11. [11]
  [9] (a) X.X. Li, L. Zhang, J.F. Lu, et al., Signal peptide mimics conjugated to peptide nucleic acid: a promising solution for improving cell membrane permeability, Bioconjug. Chem. 14 (2003) 153-157;
12. [12]
  (b) C.P. Chen, L.R. Zhang, Y.F. Peng, et al., A concise method for the preparation of peptide and arginine-rich peptide-conjugated antisense oligonucleotide, Bioconjug. Chem. 14 (2003) 532-538;
13. [13]
  (c) C.P. Chen, X.X. Li, L.R. Zhang, et al., Synthesis of antisense oligonucleotidepeptide conjugate targeting to GLUT-1 in HepG2 and MCF-7 cells, Bioconjug. Chem. 13 (2002) 525-529;
14. [14]
  (d) Y. Liu, X.F. Wang, Y. Chen, L.H. Zhang, Z.J. Yang, A solid-phase method for peptide-siRNA conjugates based on click chemistry, Med. Chem. Commun. 3 (2012) 506-511.
15. [15]
  [10] N. Venkatesan, B.H. Kim, Peptide conjugates of oligonucleotides: synthesis and applications, Chem. Rev. 106 (2006) 3712-3761.
16. [16]
  [11] R.J. Sarma, S. Otto, J.R. Nitschke, Disulfides, imines, and metal coordination within a single system: interplay between three dynamic equilibria, Chem. A: Eur. J. 13 (2007) 9542-9546.
17. [17]
  [12] P. Lundberg, S. El-Andaloussi, T. Sü tlü, H. Johansson, U. Langel, Delivery of short interfering RNA using endosomolytic cell-penetrating peptides, FASEB J. 21 (2007) 2664-2671.
18. [18]
  [13] B.Bacsa, K.Horváti, S.Bõsze, F.Andreae, C.O.Kappe, Solid-phase synthesis of difficult peptide sequences at elevated temperatures: a critical comparison of microwave and conventional heating technologies, J. Org. Chem. 73 (2008) 7532-7542.
19. [19]
  [14] B. Gerland, J. Désiré, J. Balzarini, J.L. Décout, Anti-retroviral and cytostatic activity of 2',3'-dideoxyribonucleoside 3'-disulfides, Bioorg.Med. Chem. 16 (2008) 6824-6831.
20. [20]
  [15] J.W. Gaynor, J. Bentley, R. Cosstick, Synthesis of the 3'-thio-nucleosides and subsequent automated synthesis of oligodeoxynucleotides containing a 30-Sphosphorothiolate linkage, Nat. Protoc. 2 (2007) 3122-3135.
21. [21]
  [16] P. Alewood, D. Alewood, L. Miranda, et al., Rapid in situ neutralization protocols for Boc and Fmoc solid-phase chemistries, Methods Enzymol. 289 (1997) 14-19.
22. [22]
  [17] Q. Du, H. Thonberg, H.Y. Zhang, C. Wahlestedt, Z.C. Liang, Validating siRNA using a reporter made from synthetic DNA oligonucleotides, Biochem. Biophys. Res. Commun. 325 (2004) 243-249.
23. [23]
  [18] P.R. Clark, J.S. Pober, M.S. Kluger, Knockdown of TNFR1 by the sense strand of an ICAM-1 siRNA: dissection of an off-target effect, Nucleic Acids Res. 36 (2008) 1081-1097.
24. [24]
  [19] K.B. Tiemann, A. Höhn, S.J. Ehsani, J.J. Forman, R.P. Saetrom, Dual-targeting siRNAs, RNA 16 (2010) 1275-1284.
25. [25]
  [20] (a) F. Wang, Y. Chen, Y. Huang, et al., Synthesis, physicochemical, biological properties of oligonucleotides incorporated with amino-isonucleosides, Sci. China Chem. 55 (2012) 70-79;
26. [26]
  (b) J. Zhang, Y. Chen, Y. Huang, et al., Synthesis and properties of a novel Lisonucleosides modified oligonucleotides and siRNAs, Org. Biomol. Chem. 10 (2012) 7566-7577;
27. [27]
  (c) X.F. Wang, Y. Huang, Z.J. Yang, et al., Synthesis and biological evaluation of peptide-siRNA conjugates with phosphodiester unit as linker, Sci. China Chem., http://dx.doi.org/10.1007/s11426-013-4912-y.
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