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biogenic and synthetic polyamines bind cationic dendrimers生物和合成聚胺类阳离子聚合物
Biogenic and Synthetic Polyamines Bind Cationic Dendrimers 1 1 2,3 Jean-Sebastian Mandeville , Phillipe Bourassa , Thekkumkattil John Thomas , Heidar-Ali Tajmir- Riahi1* ´ ´ ´ ` ` ` ´ 1 Departement de Chimie-Biologie, Universite du Quebec a Trois-Rivieres, Trois-Rivieres, Quebec, Canada, 2 Department of Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, New Jersey, United States of America, 3 The Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, New Jersey, United States of America 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 K
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