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Title: Novel therapeutic agents for bone resorption. Part 1. Synthesis and protonation thermodynamics of poly(amido-amine)s containing bis-phosphonate residues.
Authors: Casolaro, Mario 
Casolaro, I.
Spreafico, A.
Capperucci, C.
Frediani, Bruno
Marcolongo, R.
Margiotta, N.
Ostuni, R.
Mendichi, R.
Samperi, F.
Ishii, T.
Ito, Y.
Issue Date: 2006
Project: None 
Two poly(amido-amine)s (oligoPAM and oligoNER) containing bis-phosphonate residues were obtained by a Michael-type polyaddition of pamidronate and neridronate to 1,4-bis(acryloyl)piperazine. The SEC (size-exclusion chromatography) and the MALDI-TOF (matrix assisted laser desorption ionization) analyses were consistent with the presence of oligomeric species (2-3 kDa) and with a narrow polydispersity index. The thermodynamic results (log Ks, -¢H°, and ¢S° obtained at 25 °C in 0.15 M NaCl) of both the oligomers and the corresponding low molecular weight precursors were in line with a cluster structure formed during the protonation of the basic nitrogen in the pamidronate. The solubility of the oligoNER with a longer aliphatic chain was improved at high pHs, allowing the evaluation of their solution properties. Preliminary biological results show that both the oligomers do not negatively affect the in vitro viability, proliferation, and cellular activity of either normal animal or human osteoblasts.
ISSN: 1525-7797
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