Biogenic and synthetic polyamines bind cationic dendrimers

Jean Sebastian Mandeville, Phillipe Bourassa, Thekkumkattil John Thomas, Heidar Ali Tajmir-Riahi

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Biogenic polyamines are essential for cell growth and differentiation, while polyamine analogues exert antitumor activity in multiple experimental model systems, including breast and lung cancer. Dendrimers are widely used for drug delivery in vitro and in vivo. We report the bindings of biogenic polyamines, spermine (spm), and spermidine (spmd), and their synthetic analogues, 3,7,11,15-tetrazaheptadecane.4HCl (BE-333) and 3,7,11,15,19-pentazahenicosane.5HCl (BE-3333) to dendrimers of different compositions, mPEG-PAMAM (G3), mPEG-PAMAM (G4) and PAMAM (G4). FTIR and UV-visible spectroscopic methods as well as molecular modeling were used to analyze polyamine binding mode, the binding constant and the effects of polyamine complexation on dendrimer stability and conformation. Structural analysis showed that polyamines bound dendrimers through both hydrophobic and hydrophilic contacts with overall binding constants of Kspm-mPEG-G3 = 7.6×104 M-1, Kspm-mPEG-PAMAM-G4 = 4.6×104 M-1, Kspm-PAMAM-G4 = 6.6×104 M-1, Kspmd-mPEG-G3 = 1.0×105 M-1, Kspmd-mPEG-PAMAM-G4 = 5.5×104 M-1, Kspmd-PAMAM-G4 = 9.2×104 M-1, KBE-333-mPEG-G3 = 4.2×104 M-1, KBe-333-mPEG-PAMAM-G4 = 3.2×104 M-1, KBE-333-PAMAM-G4 = 3.6×104 M-1, KBE-3333-mPEG-G3 = 2.2×104 M-1, KBe-3333-mPEG-PAMAM-G4 = 2.4×104 M-1, KBE-3333-PAMAM-G4 = 2.3×104 M-1. Biogenic polyamines showed stronger affinity toward dendrimers than those of synthetic polyamines, while weaker interaction was observed as polyamine cationic charges increased. The free binding energies calculated from docking studies were: -3.2 (spermine), -3.5 (spermidine) and -3.03 (BE-3333) kcal/mol, with the following order of binding affinity: spermidine-PAMAM-G-4&spermine-PAMMAM-G4&BE-3333-PAMAM-G4 consistent with spectroscopic data. Our results suggest that dendrimers can act as carrier vehicles for delivering antitumor polyamine analogues to target tissues.

Original languageEnglish (US)
Article numbere36087
JournalPLoS ONE
Volume7
Issue number4
DOIs
StatePublished - Apr 27 2012

All Science Journal Classification (ASJC) codes

  • Agricultural and Biological Sciences(all)
  • General
  • Biochemistry, Genetics and Molecular Biology(all)

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