Science China Chemistry

, Volume 56, Issue 11, pp 1542–1549 | Cite as

Synthesis and biological evaluation of peptide-siRNA conjugates with phosphodiester unit as linker

  • XiaoFeng Wang
  • Ye Huang
  • Yang Liu
  • Yue Chen
  • HongWei Jin
  • Yi Zheng
  • Quan Du
  • ZhenJun Yang
  • LiHe Zhang
Articles

Abstract

In this paper, a series of peptide-siRNA conjugates with phosphodiester unit as the linker targeting to Cdc2 gene were synthesized by solid phase stepwise strategy. The conjugation of peptides at either 3′-terminus of siCdc2 bring no change to the classical A-form of RNA duplex, but slightly compromise the thermodynamic stability. Peptide conjugation at the 3′-terminus of sense strand could improve the serum stability obviously, however, the opposite peptide conjugation at the 3′-terminus of antisense strand shows no such influence. According to the results of artificial silencing activity assay system, peptide conjugation at 3′-terminus of antisense strand slightly weakens the silencing activity of siCdc2. But sense strand peptide conjugation exhibits similar silencing activity as native siCdc2, meanwhile, it could mitigate the unwanted off-target effect of sense strand targeting to its own mRNA.

Keywords

siRNA peptide conjugate solid synthesis 

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Copyright information

© Science China Press and Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • XiaoFeng Wang
    • 1
  • Ye Huang
    • 1
  • Yang Liu
    • 1
    • 2
  • Yue Chen
    • 1
  • HongWei Jin
    • 1
  • Yi Zheng
    • 1
  • Quan Du
    • 1
  • ZhenJun Yang
    • 1
  • LiHe Zhang
    • 1
  1. 1.The State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical SciencesPeking UniversityBeijingChina
  2. 2.CSPC Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd.ShijiazhuangChina

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