Supramolecular trap for catching polyamines in cells as an anti-tumor strategy

Nature Communications
Junyi ChenChunju Li

Abstract

Polyamines are essential for the growth of eukaryotic cells and can be dysregulated in tumors. Here we describe a strategy to deplete polyamines through host-guest encapsulation using a peptide-pillar[5]arene conjugate (P1P5A, P1 = RGDSK(N3)EEEE) as a supramolecular trap. The RGD in the peptide sequence allows the molecule to bind to integrin αvβ3-overexpressing tumor cells. The negative charged glutamic acid residues enhance the inclusion affinities between the pillar[5]arene and cationic polyamines via electrostatic interactions and facilitate the solubility of the conjugate in aqueous media. The trap P1P5A efficiently encapsulates polyamines with association constants of 105-106 M-1. We show that P1P5A has a wide spectrum of antitumor activities, and induces apoptosis via affecting the polyamine biosynthetic pathway. Experiments in vivo show that P1P5A effectively inhibits the growth of breast adenocarcinoma xenografts in female nude mice. This work reveals an approach for suppressing tumor growth by using supramolecular macrocycles to trap polyamines in tumor cells.

References

Jan 1, 1992·Pharmacology & Therapeutics·P P McCann, A E Pegg
Oct 23, 1987·Science·E Ruoslahti, M D Pierschbacher
Mar 1, 1986·The Biochemical Journal·A E Pegg
Jan 1, 1984·Annual Review of Biochemistry·C W Tabor, H Tabor
Jan 1, 1995·Annual Review of Pharmacology and Toxicology·L J Marton, A E Pegg
Jan 1, 1996·Annual Review of Cell and Developmental Biology·E Ruoslahti
Jan 5, 2001·Journal of Medicinal Chemistry·R A Casero, P M Woster
Aug 21, 2003·Journal of Cellular and Molecular Medicine·Thresia Thomas, T J Thomas
Sep 19, 2003·The Biochemical Journal·Heather M WallaceAlun Hughes
Oct 29, 2004·Nature Reviews. Cancer·Eugene W Gerner, Frank L Meyskens
Oct 6, 2005·Journal of Cellular and Molecular Medicine·Nikolaus Seiler, Francis Raul
Apr 28, 2007·Nature Reviews. Drug Discovery·Robert A Casero, Laurence J Marton
Feb 16, 2008·Angewandte Chemie·Sarah AngelosJeffrey I Zink
Mar 25, 2008·Journal of the American Chemical Society·Tomoki OgoshiYoshiaki Nakamoto
Feb 15, 2011·Methods in Molecular Biology·Anthony E Pegg, Robert A Casero
May 4, 2012·Accounts of Chemical Research·Min XueFeihe Huang
Jun 13, 2012·Journal of the American Chemical Society·Dong-Sheng GuoYu Liu
Jan 31, 2013·Chemical Communications : Chem Comm·Chunju LiXueshun Jia
Jun 29, 2013·International Journal of Molecular Sciences·Fen WangTian Xie
Feb 27, 2015·Chemical Reviews·Guocan YuFeihe Huang
Jun 23, 2016·Chemical Communications : Chem Comm·Kui YangZhichao Pei
Jun 24, 2016·Chemical Reviews·Tomoki OgoshiYoshiaki Nakamoto
Jun 6, 2018·Chemical Society Reviews·Huacheng ZhangYanli Zhao

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Citations

Jan 10, 2020·Nanoscale·Yong-Fu LiYing-Wei Yang
Aug 28, 2020·Frontiers in Chemistry·Hang SuChunju Li
Dec 19, 2019·Frontiers in Chemistry·Yuanyin JiaChunju Li
Aug 9, 2020·Chemical Communications : Chem Comm·Mingyeong ShinShim Sung Lee
Feb 14, 2020·Angewandte Chemie·Kaidi XuChunju Li
Feb 2, 2021·Chemical Society Reviews·Jiong ZhouFeihe Huang
Dec 29, 2020·Angewandte Chemie·Xue YangDavid Bardelang
Feb 17, 2021·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Fei LiJunqiu Liu
Sep 1, 2021·European Journal of Pharmacology·Qi-Zhang LiYan Ji
Sep 10, 2021·Nanoscale·Han-Wen TianDong-Sheng Guo
Nov 13, 2021·Chemical Communications : Chem Comm·Yibin ZhouDerong Cao

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Methods Mentioned

BETA
NMR
fluorescence titration
flow cytometry
transmission electron microscopy
xenograft
Assay
electrophoresis

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