Synlett 2017; 28(15): 1897-1900
DOI: 10.1055/s-0036-1588807
© Georg Thieme Verlag Stuttgart · New York

Lipid–Cell-Penetrating-Peptide Conjugates as Effective Delivery Systems

a   School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 518055, P. R. of China
Hui Zhao
a   School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 518055, P. R. of China
Yuan Tian
b   School of Life Science and Engineering, Southwest Jiaotong University, Chengdu, 611756, P. R. of China   Email:
Zi-Gang Li*
a   School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 518055, P. R. of China
› Author Affiliations
Supported by: National Natural Science Foundation of China (21102007, 21372023)
Supported by: MOST (2015DFA31590)
Supported by: Shenzhen Science and Technology Innovation Committee (SW201110018, SGLH20120928095602764, ZDSY20130331145112855, JSGG20140519105550503)
Supported by: Shenzhen Peacock Program (KQTD201103)
Further Information

Publication History

Received: 18 February 2017

Accepted after revision: 02 April 2017

Publication Date:
20 April 2017 (online)

Published as part of the Cluster Recent Advances in Protein and Peptide Synthesis


A lipid–cell-penetrating-peptide (CPP) conjugate was designed to deliver cargoes with poor cellular permeability, including peptides or small-molecule therapeutics, into cells. The lipid–CPP conjugate facilitated the cellular uptake of cargoes noncovalently through an ATP-dependent micropinocytosis mechanism. This delivery system is simple, efficient, has minimal cellular toxicity, and might be useful in a wide range of biological research.

Supporting Information

  • References

    • 1a Coster HG. Biophys. J. 1965; 5: 669
    • 1b Sharei A. Zoldan J. Adamo A. Sim WY. Cho N. Jackson E. Mao S. Schneider S. Han M.-J. Lytton-Jean A. Basto PA. Jhunjhunwala S. Lee J. Heller DA. Kang JW. Hartoularos GC. Kim KS. Anderson DG. Langer R. Jensen KF. Proc. Natl. Acad. Sci. U.S.A. 2013; 110: 2082
    • 1c Gu Z. Biswas A. Zhao M. Tang Y. Chem. Soc. Rev. 2011; 3638
    • 1d Qian Z. Liu T. Liu Y.-Y. Briesewitz R. Barrios AM. Jhiang SM. Pei D. ACS Chem. Biol. 2013; 8: 423
    • 1e Reissmann S. J. Pept. Sci. 2014; 20: 760

      For reviews, see:
    • 2a Copolovici DM. Langel K. Eriste E. Langel Ü. ACS Nano 2014; 8: 1972
    • 2b Koren E. Torchilin VP. Trends Mol. Med. 2012; 18: 385
  • 3 Fonseca SB. Pereira MP. Kelley SO. Adv. Drug Delivery Rev. 2009; 61: 953
  • 4 Di Pisa M. Chassaing G. Swiecicki JM. J. Pept. Sci. 2015; 21: 356
  • 5 Zhang P. Lock LL. Cheetham AG. Cui H. Mol. Pharmaceutics 2014; 11: 964
    • 6a Takayama K. Nakase I. Michiue H. Takeuchi T. Tomizawa K. Matsui H. Futaki S. J. Controlled Release 2009; 138: 128
    • 6b Takayama K. Hirose H. Tanaka G. Pujals S. Katayama S. Nakase I. Futaki S. Mol. Pharmaceutics 2012; 9: 1222
    • 7a Shirazi AN. Oh D. Tiwari RK. Sullivan B. Gupta A. Bothun GD. Parang K. Mol. Pharmaceutics 2013; 10: 4717
    • 7b Lehto T. Abes R. Oskolkov N. Suhorutšenko J. Copolovici D.-M. Mäger I. Viola JR. Simonson OE. Ezzat K. Guterstam P. Eriste E. Smith CI. E. Lebleu B. El Andaloussi S. Langel Ü. J. Controlled Release 2010; 141: 42
  • 8 Chu-Kung AF. Nguyen R. Bozzelli KN. Tirrell M. J. Colloid Interface Sci. 2010; 345: 160
    • 10a Sun W. Ji W. Hall JM. Hu Q. Wang C. Beisel CL. Gu Z. Angew. Chem. Int. Ed. 2015; 54: 12029
    • 10b Mo R. Sun Q. Xue J. Li N. Li W. Zhang C. Ping Q. Adv. Mater. (Weinheim, Ger.) 2012; 24: 3659
    • 10c Walensky LD. Kung AL. Escher I. Malia TJ. Barbuto S. Wright RD. Wagner G. Verdine GL. Korsmeyer SJ. Science 2004; 305: 1466
    • 12a Waksman G. Kominos D. Robertson SC. Pant N. Baltimore D. Birge RB. Cowburn D. Hanafusa H. Mayer BJ. Overduin M. Resh MD. Rios CB. Silverman L. Kuriyan J. Nature 1992; 358: 646
    • 12b Songyang Z. Shoelson SE. McGlade J. Olivier P. Pawson T. Bustelo XR. Barbacid M. Sabe H. Hanafusa H. Yi T. Ren R. Baltimore D. Ratnofsky S. Feldman RA. Cantley LC. Mol. Cell. Biol. 1994; 14: 2777
  • 13 Persidis A. Nat. Biotechnol. 1999; 17: 94
  • 14 Akiyama S. Fojo A. Hanover JA. Pastan I. Gottesman MM. Somat. Cell Mol. Genet. 1985; 11: 117