Biogenic and synthetic polyamines bind cationic dendrimers.

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 po...

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Autores principales:	Jean-Sebastian Mandeville, Phillipe Bourassa, Thekkumkattil John Thomas, Heidar-Ali Tajmir-Riahi
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/70f9c7d06ecf4b268dbae96e95d85476
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spelling	oai:doaj.org-article:70f9c7d06ecf4b268dbae96e95d854762021-11-18T07:20:26ZBiogenic and synthetic polyamines bind cationic dendrimers.1932-620310.1371/journal.pone.0036087https://doaj.org/article/70f9c7d06ecf4b268dbae96e95d854762012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22558341/?tool=EBIhttps://doaj.org/toc/1932-6203Biogenic 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 K(spm-mPEG-G3) = 7.6 × 10(4) M(-1), K(spm-mPEG-PAMAM-G4) = 4.6 × 10(4) M(-1), K(spm-PAMAM-G4) = 6.6 × 10(4) M(-1), K(spmd-mPEG-G3) = 1.0 × 10(5) M(-1), K(spmd-mPEG-PAMAM-G4) = 5.5 × 10(4) M(-1), K(spmd-PAMAM-G4) = 9.2 × 10(4) M(-1), K(BE-333-mPEG-G3) = 4.2 × 10(4) M(-1), K(Be-333-mPEG-PAMAM-G4) = 3.2 × 10(4) M(-1), K(BE-333-PAMAM-G4) = 3.6 × 10(4) M(-1), K(BE-3333-mPEG-G3) = 2.2 × 10(4) M(-1), K(Be-3333-mPEG-PAMAM-G4) = 2.4 × 10(4) M(-1), K(BE-3333-PAMAM-G4) = 2.3 × 10(4) 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.Jean-Sebastian MandevillePhillipe BourassaThekkumkattil John ThomasHeidar-Ali Tajmir-RiahiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 4, p e36087 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jean-Sebastian Mandeville Phillipe Bourassa Thekkumkattil John Thomas Heidar-Ali Tajmir-Riahi Biogenic and synthetic polyamines bind cationic dendrimers.
description	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 K(spm-mPEG-G3) = 7.6 × 10(4) M(-1), K(spm-mPEG-PAMAM-G4) = 4.6 × 10(4) M(-1), K(spm-PAMAM-G4) = 6.6 × 10(4) M(-1), K(spmd-mPEG-G3) = 1.0 × 10(5) M(-1), K(spmd-mPEG-PAMAM-G4) = 5.5 × 10(4) M(-1), K(spmd-PAMAM-G4) = 9.2 × 10(4) M(-1), K(BE-333-mPEG-G3) = 4.2 × 10(4) M(-1), K(Be-333-mPEG-PAMAM-G4) = 3.2 × 10(4) M(-1), K(BE-333-PAMAM-G4) = 3.6 × 10(4) M(-1), K(BE-3333-mPEG-G3) = 2.2 × 10(4) M(-1), K(Be-3333-mPEG-PAMAM-G4) = 2.4 × 10(4) M(-1), K(BE-3333-PAMAM-G4) = 2.3 × 10(4) 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.
format	article
author	Jean-Sebastian Mandeville Phillipe Bourassa Thekkumkattil John Thomas Heidar-Ali Tajmir-Riahi
author_facet	Jean-Sebastian Mandeville Phillipe Bourassa Thekkumkattil John Thomas Heidar-Ali Tajmir-Riahi
author_sort	Jean-Sebastian Mandeville
title	Biogenic and synthetic polyamines bind cationic dendrimers.
title_short	Biogenic and synthetic polyamines bind cationic dendrimers.
title_full	Biogenic and synthetic polyamines bind cationic dendrimers.
title_fullStr	Biogenic and synthetic polyamines bind cationic dendrimers.
title_full_unstemmed	Biogenic and synthetic polyamines bind cationic dendrimers.
title_sort	biogenic and synthetic polyamines bind cationic dendrimers.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/70f9c7d06ecf4b268dbae96e95d85476
work_keys_str_mv	AT jeansebastianmandeville biogenicandsyntheticpolyaminesbindcationicdendrimers AT phillipebourassa biogenicandsyntheticpolyaminesbindcationicdendrimers AT thekkumkattiljohnthomas biogenicandsyntheticpolyaminesbindcationicdendrimers AT heidaralitajmirriahi biogenicandsyntheticpolyaminesbindcationicdendrimers
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Biogenic and synthetic polyamines bind cationic dendrimers.

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