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

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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.

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Authors and Affiliations

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

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

  2. CSPC Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd., Shijiazhuang, 050035, China

    Yang Liu

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  1. XiaoFeng Wang
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  2. Ye Huang
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  3. Yang Liu
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  4. Yue Chen
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  5. HongWei Jin
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  6. Yi Zheng
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  7. Quan Du
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  8. ZhenJun Yang
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  9. LiHe Zhang
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Correspondence to ZhenJun Yang.

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These authors contributed equally to this work

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Wang, X., Huang, Y., Liu, Y. et al. Synthesis and biological evaluation of peptide-siRNA conjugates with phosphodiester unit as linker. Sci. China Chem. 56, 1542–1549 (2013). https://doi.org/10.1007/s11426-013-4912-y

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  • DOI: https://doi.org/10.1007/s11426-013-4912-y

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